HIV InfectionsPhase 1NCT03984812
Evaluation of the Safety, Tolerability and Pharmacokinetics (PK) of GSK3732394 First-Time-in-Human (FTIH) Study
A Phase 1 study testing GSK3732394 in people with HIV Infections, run by ViiV Healthcare at 1 site in United States.
Trial summary
This is a phase 1, 2-part, double-blind (sponsor-unblinded), randomized, placebo-controlled, FTIH study, that includes both single-ascending and multiple-ascending dose phase to assess the safety, tolerability, and pharmacokinetic (PK)/pharmacodynamic (PD) attributes of GSK3732394 in healthy subjects. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- GSK3732394
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jun 2019to 23 Mar 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
- Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- Subjects who are able to understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions
- Body mass index within the range 19 to 30 kilogram per meter square (kg/m2) inclusive, in addition to a weight range of 50kg to 100kg.
- Male and female healthy volunteers.
- All male subjects must agree to use contraception during the treatment period and for at least 100 days after the last dose of study treatment and refrain from donating sperm during this period.
Show all 9Show fewer
- A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies; Not a woman of childbearing potential (WOCBP), A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 28 days prior to first dose, and 40 days after, the last dose of study treatment.
- Capable of giving signed informed consent.
- A signed and dated written informed consent must be completed prior to the subject's entry into the study.
Who cannot join
- Subject has a history or presence of cardiovascular, dermatological, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
- Subject has abnormal blood pressure (as determined by the investigator).
- Subject had symptomatic herpes zoster within 3 months prior to screening.
- Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, TB testing that includes a positive tuberculin skin test [TST]; defined as a skin induration greater than 5 millimeter [mm] at 48 to 72 hours,and regardless of Bacillus Calmette-Guerin [BCG] or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold test.
- Subjects with lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
- Subjects who had breast cancer within the past 10 years.
Show all 32Show fewer
- Subjects who had history of severe injection site reaction (i.e., required emergency care or hospitalization) following any prior injection, including reaction to vaccines.
- Subjects with history of clinically significant allergy or prior hypersensitivity including those with a documented yeast allergy.
- Subjects with history of, or current concern for, a chronic immune deficiency disorder including, but not limited to: diabetes, sickle cell anemia, and malnutrition.
- Subjects having alanine transaminase (ALT) greater than 1.1 x upper limit of normal (ULN).
- Subjects with Hemoglobin levels below the normal range.
- Subjects with Platelet count <130,000 per cubic millimeters.
- Subjects with Creatinine clearance (CrCL) <90 milliliters per minute.
- Subjects with bilirubin greater than 1.1xULN (isolated bilirubin greater than 1.1xULN is acceptable if bilirubin is fractionated and direct bilirubin greater than 35%).
- Subjects who has current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Subjects having Fridericia QT correction formula (QTcF) greater than 450 milliseconds (msec).
- Subjects who had intended use of over-the-counter or prescription medication within 7 days prior to dosing.
- Subjects who had live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the study.
- Subjects who had treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing.
- Subjects who had exposure to immune-modulating medications (including corticosteroids) within 30-days of Screening.
- Subjects whose participation in the study would result in loss of blood or blood products in excess of 500 (milliliter) mL within 56 days.
- Subjects who had Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Subjects with current enrollment or past participation within the last 30 days before signing of consent in this or any other clinical study involving an investigational study intervention or any other type of medical research.
- Absolute CD4+ T-cell count and CD4 percent (CD4%) outside of the normal range for the reference laboratory (to be confirmed at baseline, e.g., Day -1).
- Subjects who had presence of Hepatitis B surface antigen (HBsAg) at screening.
- Subjects with positive Hepatitis C antibody test result at screening.
- Subjects with positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention.
- Subjects with positive pre-study drug/alcohol screen.
- Subjects with positive human immunodeficiency virus (HIV) antibody test.
- Subjects with history of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 14 units. One unit is equivalent to 8 grams (g) of alcohol: a half pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- Subjects with urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening.
- Subjects who has sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK3732394 in Healthy Participants
This is a phase 1, 2-part, double-blind (sponsor-unblinded), randomized, placebo-controlled, FTIH study, that includes both single-ascending and multiple-ascending dose phase to assess the safety, tolerability, and pharmacokinetic (PK)/pharmacodynamic (PD) attributes of GSK3732394 in healthy subjects. The data gathered in this study will further enable clinical development of GSK3732394 in HIV-infected subjects. Approximately 72 healthy subjects will be randomized in the FTIH study. Part 1 will be the single ascending dose (SAD) phase and Part 2 will be the multiple ascending dose (MAD) phase. Each subject in the SAD cohort will receive a single dose of blinded GSK3732394 or blinded placebo (PBO) in 6:2 ratio. Part 1 will consist of five ascending single-dose cohorts with an additional expansion cohort included as needed. Part 2 will consist of up to three ascending repeat-dose cohorts (MAD Cohorts 1, 2, and 3), randomized to four weekly doses of blinded GSK3732394 or blinded PBO in 6:2 ratio to be administered on Days 1, 8, 15, and 22.
- Conditions
- HIV Infections
- Being tested
- GSK3732394, Placebo
- Keywords
- DAIDS, FTIH, HIV-1, MAD, SAD
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK3732394Drug
It is composed of an anti-CD4 adnectin, an anti-N17 adnectin, and a peptide inhibitor. This will be provided as a solution for injection in 1 (milliliter) mL glass vials with the unit dose strength of 100 mg/mL
PlaceboDrug
Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.
| Study group | Role | What they receive |
|---|---|---|
| Part 1,Cohort 1:Subjects receiving blinded GSK3732394 10mg/PBO | Experimental | GSK3732394 10 milligram (mg) or PBO will be administered by subcutaneous (SC) injection to the subjects. Receives: Drug: GSK3732394; Drug: Placebo |
| Part 1,Cohort 2:Subjects receiving blinded GSK3732394 40mg/PBO | Experimental | GSK3732394 40 mg or PBO will be administered by SC injection to the subjects. This is projected dose, dose will be based on PK/PD results from preceding dosing cohorts. Receives: Drug: GSK3732394; Drug: Placebo |
| Part1,Cohort 3:Subjects receiving blinded GSK3732394 130mg/PBO | Experimental | GSK3732394 130 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 3 will be based on PK/PD results from preceding dosing cohorts. Receives: Drug: GSK3732394 |
| Part1,Cohort 4:Subjects receiving blinded GSK3732394 350mg/PBO | Experimental | GSK3732394 350 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 4 will be based on PK/PD results from preceding dosing cohorts. Receives: Drug: GSK3732394; Drug: Placebo |
| Part1,Cohort5: Subjects receiving blinded GSK3732394 600mg/PBO | Experimental | GSK3732394 600 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 5 will be based on PK/PD results from preceding dosing cohorts. Receives: Drug: GSK3732394; Drug: Placebo |
| Part1,Cohort6: Subjects receiving blinded GSK3732394 800mg/PBO | Experimental | GSK3732394 800 mg or PBO will be administered by SC injection to the subjects. This is a projected dose and will be given if necessary. The dose administered in Part 1, Cohort 6 (if necessary) will be based on PK/PD results from preceding dosing cohorts. Receives: Drug: GSK3732394; Drug: Placebo |
| Part2,Cohort1: Subjects receiving blinded GSK3732394 130mg/PBO | Experimental | GSK3732394 130 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The dose administered in Part 2, Cohort 1 will be based on PK/PD results from preceding dosing cohorts. Receives: Drug: GSK3732394; Drug: Placebo |
| Part2,Cohort2: Subjects receiving blinded GSK3732394 400mg/PBO | Experimental | GSK3732394 400 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The administered dose in Part 2, Cohort 2 will be based on PK/PD results from preceding dosing cohorts. Receives: Drug: GSK3732394; Drug: Placebo |
| Part2,Cohort3: Subjects receiving blinded GSK3732394 600mg/PBO | Experimental | GSK3732394 600 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The administered dose in Part 2, Cohort 3 will be based on PK/PD results from preceding dosing cohorts and will not exceed the maximum exposure observed in SAD (Part 1). Receives: Drug: GSK3732394; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Number of Participants With Non-serious Adverse Event (SAEs) and SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgement. Number of participants with common more than or equal to (>=)5 percent (%) non-serious AEs and SAEs are presented.
Measured: Up to Day 28
Part 2: Number of Participants With Non-SAEs and SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgement. All AEs were planned to be collected from the start of treatment until the follow-up visit.
Measured: Up to Day 49
Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline
Blood samples were collected for the analysis of following clinical chemistry parameters: Glucose, alkaline phosphatase, alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), direct bilirubin, total bilirubin, calcium, creatinine, potassium, lipase and sodium. The clinical chemistry abnormalities were graded using the Division of Acquired immunodeficiency syndrome (DAIDS) criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. Baseline is defined as the latest pre-dose assessment. Number of participants with clinical chemistry parameters by maximum grade increase post-Baseline is presented.
Measured: Up to Day 28
Part 2: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline
Blood samples were planned to be collected for the analysis of the following clinical chemistry parameters: Glucose, alkaline phosphatase, ALT, amylase, AST, direct and total bilirubin, calcium, creatinine, potassium, lipase and sodium. Baseline is defined as the latest pre-dose assessment.
Measured: Up to Day 49
Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline
Blood samples were collected for the analysis of following hematology parameters: Cluster of differentiation (CD) 4 cells, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The hematology abnormalities were graded using the DAIDS criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. Baseline is defined as the latest pre-dose assessment. Number of participants with hematology parameters by maximum grade increase post-Baseline is presented.
Measured: Up to Day 28
Part 2: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline
Blood samples were planned to be collected for the analysis of the following hematology parameters: CD4 cells, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. Baseline is defined as the latest pre-dose assessment.
Measured: Up to Day 49
Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline
Urine samples were collected for the analysis of urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. The urinalysis abnormalities were graded using the DAIDS criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Baseline is defined as the latest pre-dose assessment. Number of participants with urinalysis parameters by any increase in discrete or character values post Baseline is presented.
Measured: Up to Day 28
Part 2: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline
Urine samples were planned to be collected for the analysis of urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. Baseline is defined as the latest pre-dose assessment.
Measured: Up to Day 49
Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline
Pulse rate was measured in a semi-supine position after 5 minutes of rest. Participants are counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose value category are unchanged (e.g., High to High), or whose value became within range, are recorded in the "To within Range or No Change" category. Participants with missing Baseline value are assumed to have within range value. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. Number of participants with pulse rate change to low or to high and no change post Baseline is presented.
Measured: Up to Day 28
Part 2: Number of Participants With Worst Case Pulse Rate Post Baseline
Pulse rate was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment.
Measured: Up to Day 49
Part 1: Change From Baseline in Body Temperature
Body temperature was measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Measured: Baseline and at Day 1 (1, 2, 4, 8, 12 hours), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in Body Temperature
Body temperature was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Measured: Baseline and Up to Day 49
Part 1: Change From Baseline in Respiratory Rate
Respiratory rate was measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Measured: Baseline and at Day 1 (1, 2, 4, 8, 12 hours), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in Respiratory Rate
Respiratory rate was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Measured: Baseline and Up to Day 49
Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline
SBP and DBP was measured in a semi-supine position after 5 minutes of rest. Participants are counted in the worst case category that their value changes to low, within range or no change, or high), unless there is no change in their category. Participants whose value category are unchanged (e.g., High to High), or whose value became within range, are recorded in the "To within Range or No Change" category. Participants with missing Baseline value are assumed to have within range value. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. Number of participants with SBP and DBP change to low and to high and no change post Baseline is presented.
Measured: Up to Day 28
Part 2: Number of Participants With Worst Case SBP and DBP Post Baseline
SBP and DBP was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment.
Measured: Up to Day 49
Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of 5 minutes. Twelve lead ECGs were obtained by using an automated ECG machine. Number of participants with clinical significant abnormal ECG findings are presented.
Measured: Pre-dose, 4, 12 hours on Day 1, 24 hours on Day 2, Days 8, 14, 17 and 28
Part 2: Number of Participants With Clinical Significant Abnormal ECG Findings
12-lead ECG recordings was planned to be measured.
Measured: Up to Day 49
Secondary outcomes (37)
Part 1: Area Under the Plasma Concentration Time Curve From Zero to t (AUC[0-t]) Following Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: AUC(0-t) After Repeat Dosing of GSK3732394 in First Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Measured: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) Following Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: AUC(0-infinity) After Repeat Dosing of GSK3732394 in First Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Measured: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 1: Maximum Observed Concentration (Cmax) Following Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Cmax After Repeat Dosing of GSK3732394 in First Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Measured: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 2: Cmax After Repeat Dosing of GSK3732394 in Last Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Measured: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were calculated using standard non-compartmental analysis.
Measured: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Tmax After Repeat Dosing of GSK3732394 in First Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Measured: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 2: Tmax After Repeat Dosing of GSK3732394 in Last Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Measured: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 1: Lag Time Before Observation of Drug Concentrations (Tlag) After Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were calculated using standard non-compartmental analysis.
Measured: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Tlag After Repeat Dosing of GSK3732394 in First Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Measured: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 1: Last Observable Concentration (Clast) After Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 1: Time of Last Observable Concentration (Tlast) After Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 1: Apparent Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: T1/2 After Repeat Dosing of GSK3732394 in Last Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Measured: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 1: Apparent Clearance (CL/F) After Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.
Measured: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: CL/F After Repeat Dosing of GSK3732394 in Last Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Measured: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 2: Area Under the Concentration Time Curve at Steady State Within the Dosing Interval (AUC[0-tau]) After Repeat Dosing of GSK3732394 in Last Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Measured: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 2: Trough Concentration (Ctrough) After Repeat Dosing of GSK3732394 in Last Week
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.
Measured: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 2: Accumulation Ratio Using AUC(0-tau) (RAUC[0-tau]) After Repeat Dosing of GSK3732394
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RAUC(0-tau) was planned to be calculated as the ratio of AUC(0-tau) on week 4 to AUC(0-tau) on week 1 .
Measured: Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28
Part 2: Accumulation Ratio Using Cmax (RCmax) After Repeat Dosing of GSK3732394
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RCmax was planned to be calculated as the ratio of Cmax on Week 4 to Cmax on Week 1.
Measured: Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28
Part 2: Accumulation Ratio Using Ctrough (RCtrough) After Repeat Dosing of GSK3732394
Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RCtrough was planned to be calculated as the ratio of Ctrough on Week 4 to Ctrough on Week 1.
Measured: Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28
Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for Pharmacodynamic (PD) analysis of CD4 receptors occupied by GSK3732394 on CD4+ T cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Measured: Baseline, Day 1 (0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in Percent of CD4 RO After Multiple Dose Administration of GSK3732394
Blood samples were planned to be collected at indicated time points for PD analysis of CD4 receptors occupied by GSK3732394 on CD4+ T cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Measured: Baseline and up to Day 49
Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for analysis of CD3+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Measured: Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in CD3+ Cells Following Multiple Dose Administration of GSK3732394
Blood samples were planned to be collected at indicated time points for analysis of CD3+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Measured: Baseline and up to Day 49
Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for analysis of CD4+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Measured: Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in CD4+ Cells Following Multiple Dose Administration of GSK3732394
Blood samples were planned to be collected at indicated time points for analysis of CD4+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Measured: Baseline and up to Day 49
Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for analysis of CD8+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Measured: Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in CD8+ Cells Following Multiple Dose Administration of GSK3732394
Blood samples were planned to be collected at indicated time points for analysis of CD8+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Measured: Baseline and up to Day 49
Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394
Blood samples were collected at indicated time points for analysis of CD4+ cell MFI. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Measured: Baseline, Day 1 (0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in CD4+ Cell MFI Following Multiple Dose Administration of GSK3732394
Blood samples were planned to be collected at indicated time points for analysis of CD4+ cell MFI. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Measured: Baseline and up to Day 49
Part 1: Number of Participants With Anti-GSK3732394 Antibodies on Day 28
Serum samples were collected to analyze antibodies against GSK3732394. The presence of anti-GSK3732394 antibodies was determined in serum samples using a validated bioanalytical method, which included a screening assay, confirmation assay and titer analysis. Positive samples were further characterized with additional assays to determine the specificity of the anti-GSK3732394 antibodies. Number of participants with presence of anti-GSK3732394 antibodies are presented.
Measured: Day 28
Part 2: Number of Participants With Anti-GSK3732394 Antibodies
Serum samples were planned to be collected to analyze antibodies against GSK3732394.
Measured: Up to Day 49
Part 1: Titer of Anti-drug Antibodies (ADAs) Against GSK3732394 on Day 28
Serum samples were collected to analyze the titers of antibodies against GSK3732394. The presence of anti-GSK3732394 antibodies was determined in serum samples using a validated bioanalytical method, which included a screening assay, confirmation assay and titer analysis. Positive samples were further characterized with additional assays to determine the specificity of the anti-GSK3732394 antibodies. Positive samples were titrated to obtain the titers of antibodies.
Measured: Day 28
Part 2: Titer of ADAs Against GSK3732394
Serum samples were planned to be collected to analyze the titers of antibodies against GSK3732394.
Measured: Up to Day 49
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2019
- Study start17 Jun 2019
- Primary completion23 Mar 2020
- Study completion23 Mar 2020
Why it stopped: The study was terminated early (following completion of SAD Cohort 3; 80 mg) based on PK/PD modelling which demonstrated the medicine's intended target profile was not achievable.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by ViiV HealthcareThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In Part 1 of the study each of the subjects in the SAD cohorts (SAD Cohorts 1-5; SAD Cohort 6 is a possible expansion cohort that will be added as needed) will receive a single dose of blinded GSK3732394 or blinded PBO (GSK3732394: PBO = 6:2), per their randomization assignment. Part 2 will consist of up to three ascending repeat-dose cohorts (MAD Cohorts 1, 2, and 3), each with 8 subjects (blinded GSK3732394: blinded PBO = 6:2) will receive four weekly doses of GSK3732394 or PBO on Days 1, 8, 15, and 22.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- ViiV Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, ViiV Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03984812
- Sponsor's protocol ID
- 207863
- Status last verified
- Oct 2021
- First submitted
- 10 Jun 2019
- Last updated
- 25 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
Krystal M, Chabria S, Austin D, Wolstenholme A, Wensel D, Lataillade M, Abberbock J, Baker M, Ackerman P. A Phase 1 randomized study of GSK3732394, an investigational long-acting biologic treatment regimen for HIV-1 infection. Antivir Ther. 2022 Oct;27(5):13596535221131164. doi: 10.1177/13596535221131164.
PubMed 36191080
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK3732394 in Healthy Participants
- ClinicalTrials.gov ID
- NCT03984812
- Acronym / sponsor ID
- 207863
- Conditions
- HIV Infections
- Keywords
- DAIDS, FTIH, HIV-1, MAD, SAD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early (following completion of SAD Cohort 3; 80 mg) based on PK/PD modelling which demonstrated the medicine's intended target profile was not achievable.
- Enrolment
- 24 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Study start
- 17 Jun 2019 (actual)
- Primary completion
- 23 Mar 2020 (actual)
- Study completion
- 23 Mar 2020 (actual)
- First posted
- 13 Jun 2019 (actual)
- Results
- Posted 12 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 1, 2-part, double-blind (sponsor-unblinded), randomized, placebo-controlled, FTIH study, that includes both single-ascending and multiple-ascending dose phase to assess the safety, tolerability, and pharmacokinetic (PK)/pharmacodynamic (PD) attributes of GSK3732394 in healthy subjects. The data gathered in this study will further enable clinical development of GSK3732394 in HIV-infected subjects. Approximately 72 healthy subjects will be randomized in the FTIH study. Part 1 will be the single ascending dose (SAD) phase and Part 2 will be the multiple ascending dose (MAD) phase. Each subject in the SAD cohort will receive a single dose of blinded GSK3732394 or blinded placebo (PBO) in 6:2 ratio. Part 1 will consist of five ascending single-dose cohorts with an additional expansion cohort included as needed. Part 2 will consist of up to three ascending repeat-dose cohorts (MAD Cohorts 1, 2, and 3), randomized to four weekly doses of blinded GSK3732394 or blinded PBO in 6:2 ratio to be administered on Days 1, 8, 15, and 22.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 9
- Model description
- In Part 1 of the study each of the subjects in the SAD cohorts (SAD Cohorts 1-5; SAD Cohort 6 is a possible expansion cohort that will be added as needed) will receive a single dose of blinded GSK3732394 or blinded PBO (GSK3732394: PBO = 6:2), per their randomization assignment. Part 2 will consist of up to three ascending repeat-dose cohorts (MAD Cohorts 1, 2, and 3), each with 8 subjects (blinded GSK3732394: blinded PBO = 6:2) will receive four weekly doses of GSK3732394 or PBO on Days 1, 8, 15, and 22.
| Arm | Type | Receives |
|---|---|---|
| Part 1,Cohort 1:Subjects receiving blinded GSK3732394 10mg/PBO | Experimental | Drug: GSK3732394, Drug: PlaceboGSK3732394 10 milligram (mg) or PBO will be administered by subcutaneous (SC) injection to the subjects. |
| Part 1,Cohort 2:Subjects receiving blinded GSK3732394 40mg/PBO | Experimental | Drug: GSK3732394, Drug: PlaceboGSK3732394 40 mg or PBO will be administered by SC injection to the subjects. This is projected dose, dose will be based on PK/PD results from preceding dosing cohorts. |
| Part1,Cohort 3:Subjects receiving blinded GSK3732394 130mg/PBO | Experimental | Drug: GSK3732394GSK3732394 130 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 3 will be based on PK/PD results from preceding dosing cohorts. |
| Part1,Cohort 4:Subjects receiving blinded GSK3732394 350mg/PBO | Experimental | Drug: GSK3732394, Drug: PlaceboGSK3732394 350 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 4 will be based on PK/PD results from preceding dosing cohorts. |
| Part1,Cohort5: Subjects receiving blinded GSK3732394 600mg/PBO | Experimental | Drug: GSK3732394, Drug: PlaceboGSK3732394 600 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 5 will be based on PK/PD results from preceding dosing cohorts. |
| Part1,Cohort6: Subjects receiving blinded GSK3732394 800mg/PBO | Experimental | Drug: GSK3732394, Drug: PlaceboGSK3732394 800 mg or PBO will be administered by SC injection to the subjects. This is a projected dose and will be given if necessary. The dose administered in Part 1, Cohort 6 (if necessary) will be based on PK/PD results from preceding dosing cohorts. |
| Part2,Cohort1: Subjects receiving blinded GSK3732394 130mg/PBO | Experimental | Drug: GSK3732394, Drug: PlaceboGSK3732394 130 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The dose administered in Part 2, Cohort 1 will be based on PK/PD results from preceding dosing cohorts. |
| Part2,Cohort2: Subjects receiving blinded GSK3732394 400mg/PBO | Experimental | Drug: GSK3732394, Drug: PlaceboGSK3732394 400 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The administered dose in Part 2, Cohort 2 will be based on PK/PD results from preceding dosing cohorts. |
| Part2,Cohort3: Subjects receiving blinded GSK3732394 600mg/PBO | Experimental | Drug: GSK3732394, Drug: PlaceboGSK3732394 600 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The administered dose in Part 2, Cohort 3 will be based on PK/PD results from preceding dosing cohorts and will not exceed the maximum exposure observed in SAD (Part 1). |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Subjects must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
- Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- Subjects who are able to understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions
- Body mass index within the range 19 to 30 kilogram per meter square (kg/m2) inclusive, in addition to a weight range of 50kg to 100kg.
- Male and female healthy volunteers.
Key exclusion criteria (32 listed)
- Subject has a history or presence of cardiovascular, dermatological, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
- Subject has abnormal blood pressure (as determined by the investigator).
- Subject had symptomatic herpes zoster within 3 months prior to screening.
- Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, TB testing that includes a positive tuberculin skin test [TST]; defined as a skin induration greater than 5 millimeter [mm] at 48 to 72 hours,and regardless of Bacillus Calmette-Guerin [BCG] or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold test.
- Subjects with lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK3732394It is composed of an anti-CD4 adnectin, an anti-N17 adnectin, and a peptide inhibitor. This will be provided as a solution for injection in 1 (milliliter) mL glass vials with the unit dose strength of 100 mg/mL | Drug | Part 1,Cohort 1:Subjects receiving blinded GSK3732394 10mg/PBO, Part 1,Cohort 2:Subjects receiving blinded GSK3732394 40mg/PBO, Part1,Cohort 3:Subjects receiving blinded GSK3732394 130mg/PBO, Part1,Cohort 4:Subjects receiving blinded GSK3732394 350mg/PBO, Part1,Cohort5: Subjects receiving blinded GSK3732394 600mg/PBO, Part1,Cohort6: Subjects receiving blinded GSK3732394 800mg/PBO, Part2,Cohort1: Subjects receiving blinded GSK3732394 130mg/PBO, Part2,Cohort2: Subjects receiving blinded GSK3732394 400mg/PBO, Part2,Cohort3: Subjects receiving blinded GSK3732394 600mg/PBO |
| PlaceboPlacebo will comprise of 0.9% weight per volume (w/v) sodium chloride. | Drug | Part 1,Cohort 1:Subjects receiving blinded GSK3732394 10mg/PBO, Part 1,Cohort 2:Subjects receiving blinded GSK3732394 40mg/PBO, Part1,Cohort 4:Subjects receiving blinded GSK3732394 350mg/PBO, Part1,Cohort5: Subjects receiving blinded GSK3732394 600mg/PBO, Part1,Cohort6: Subjects receiving blinded GSK3732394 800mg/PBO, Part2,Cohort1: Subjects receiving blinded GSK3732394 130mg/PBO, Part2,Cohort2: Subjects receiving blinded GSK3732394 400mg/PBO, Part2,Cohort3: Subjects receiving blinded GSK3732394 600mg/PBO |
Primary outcome
Part 1: Number of Participants With Non-serious Adverse Event (SAEs) and SAEs
Time frame: Up to Day 28
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgement. Number of participants with common more than or equal to (>=)5 percent (%) non-serious AEs and SAEs are presented.
Part 2: Number of Participants With Non-SAEs and SAEs
Time frame: Up to Day 49
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgement. All AEs were planned to be collected from the start of treatment until the follow-up visit.
Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline
Time frame: Up to Day 28
Blood samples were collected for the analysis of following clinical chemistry parameters: Glucose, alkaline phosphatase, alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), direct bilirubin, total bilirubin, calcium, creatinine, potassium, lipase and sodium. The clinical chemistry abnormalities were graded using the Division of Acquired immunodeficiency syndrome (DAIDS) criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. Baseline is defined as the latest pre-dose assessment. Number of participants with clinical chemistry parameters by maximum grade increase post-Baseline is presented.
Part 2: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline
Time frame: Up to Day 49
Blood samples were planned to be collected for the analysis of the following clinical chemistry parameters: Glucose, alkaline phosphatase, ALT, amylase, AST, direct and total bilirubin, calcium, creatinine, potassium, lipase and sodium. Baseline is defined as the latest pre-dose assessment.
Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline
Time frame: Up to Day 28
Blood samples were collected for the analysis of following hematology parameters: Cluster of differentiation (CD) 4 cells, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The hematology abnormalities were graded using the DAIDS criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. Baseline is defined as the latest pre-dose assessment. Number of participants with hematology parameters by maximum grade increase post-Baseline is presented.
Part 2: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline
Time frame: Up to Day 49
Blood samples were planned to be collected for the analysis of the following hematology parameters: CD4 cells, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. Baseline is defined as the latest pre-dose assessment.
Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline
Time frame: Up to Day 28
Urine samples were collected for the analysis of urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. The urinalysis abnormalities were graded using the DAIDS criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Baseline is defined as the latest pre-dose assessment. Number of participants with urinalysis parameters by any increase in discrete or character values post Baseline is presented.
Part 2: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline
Time frame: Up to Day 49
Urine samples were planned to be collected for the analysis of urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. Baseline is defined as the latest pre-dose assessment.
Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline
Time frame: Up to Day 28
Pulse rate was measured in a semi-supine position after 5 minutes of rest. Participants are counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose value category are unchanged (e.g., High to High), or whose value became within range, are recorded in the "To within Range or No Change" category. Participants with missing Baseline value are assumed to have within range value. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. Number of participants with pulse rate change to low or to high and no change post Baseline is presented.
Part 2: Number of Participants With Worst Case Pulse Rate Post Baseline
Time frame: Up to Day 49
Pulse rate was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment.
Part 1: Change From Baseline in Body Temperature
Time frame: Baseline and at Day 1 (1, 2, 4, 8, 12 hours), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Body temperature was measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Part 2: Change From Baseline in Body Temperature
Time frame: Baseline and Up to Day 49
Body temperature was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 1: Change From Baseline in Respiratory Rate
Time frame: Baseline and at Day 1 (1, 2, 4, 8, 12 hours), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Respiratory rate was measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Part 2: Change From Baseline in Respiratory Rate
Time frame: Baseline and Up to Day 49
Respiratory rate was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline
Time frame: Up to Day 28
SBP and DBP was measured in a semi-supine position after 5 minutes of rest. Participants are counted in the worst case category that their value changes to low, within range or no change, or high), unless there is no change in their category. Participants whose value category are unchanged (e.g., High to High), or whose value became within range, are recorded in the "To within Range or No Change" category. Participants with missing Baseline value are assumed to have within range value. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. Number of participants with SBP and DBP change to low and to high and no change post Baseline is presented.
Part 2: Number of Participants With Worst Case SBP and DBP Post Baseline
Time frame: Up to Day 49
SBP and DBP was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment.
Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings
Time frame: Pre-dose, 4, 12 hours on Day 1, 24 hours on Day 2, Days 8, 14, 17 and 28
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of 5 minutes. Twelve lead ECGs were obtained by using an automated ECG machine. Number of participants with clinical significant abnormal ECG findings are presented.
Part 2: Number of Participants With Clinical Significant Abnormal ECG Findings
Time frame: Up to Day 49
12-lead ECG recordings was planned to be measured.
37 secondary outcomes
Part 1: Area Under the Plasma Concentration Time Curve From Zero to t (AUC[0-t]) Following Single Dose Administration of GSK3732394
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: AUC(0-t) After Repeat Dosing of GSK3732394 in First Week
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) Following Single Dose Administration of GSK3732394
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: AUC(0-infinity) After Repeat Dosing of GSK3732394 in First Week
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 1: Maximum Observed Concentration (Cmax) Following Single Dose Administration of GSK3732394
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Cmax After Repeat Dosing of GSK3732394 in First Week
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 2: Cmax After Repeat Dosing of GSK3732394 in Last Week
Time frame: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3732394
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Tmax After Repeat Dosing of GSK3732394 in First Week
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 2: Tmax After Repeat Dosing of GSK3732394 in Last Week
Time frame: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 1: Lag Time Before Observation of Drug Concentrations (Tlag) After Single Dose Administration of GSK3732394
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Tlag After Repeat Dosing of GSK3732394 in First Week
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 1: Last Observable Concentration (Clast) After Single Dose Administration of GSK3732394
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 1: Time of Last Observable Concentration (Tlast) After Single Dose Administration of GSK3732394
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 1: Apparent Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3732394
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: T1/2 After Repeat Dosing of GSK3732394 in Last Week
Time frame: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 1: Apparent Clearance (CL/F) After Single Dose Administration of GSK3732394
Time frame: Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: CL/F After Repeat Dosing of GSK3732394 in Last Week
Time frame: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 2: Area Under the Concentration Time Curve at Steady State Within the Dosing Interval (AUC[0-tau]) After Repeat Dosing of GSK3732394 in Last Week
Time frame: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 2: Trough Concentration (Ctrough) After Repeat Dosing of GSK3732394 in Last Week
Time frame: Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 2: Accumulation Ratio Using AUC(0-tau) (RAUC[0-tau]) After Repeat Dosing of GSK3732394
Time frame: Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28
Part 2: Accumulation Ratio Using Cmax (RCmax) After Repeat Dosing of GSK3732394
Time frame: Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28
Part 2: Accumulation Ratio Using Ctrough (RCtrough) After Repeat Dosing of GSK3732394
Time frame: Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28
Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394
Time frame: Baseline, Day 1 (0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in Percent of CD4 RO After Multiple Dose Administration of GSK3732394
Time frame: Baseline and up to Day 49
Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394
Time frame: Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in CD3+ Cells Following Multiple Dose Administration of GSK3732394
Time frame: Baseline and up to Day 49
Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394
Time frame: Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in CD4+ Cells Following Multiple Dose Administration of GSK3732394
Time frame: Baseline and up to Day 49
Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394
Time frame: Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in CD8+ Cells Following Multiple Dose Administration of GSK3732394
Time frame: Baseline and up to Day 49
Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394
Time frame: Baseline, Day 1 (0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in CD4+ Cell MFI Following Multiple Dose Administration of GSK3732394
Time frame: Baseline and up to Day 49
Part 1: Number of Participants With Anti-GSK3732394 Antibodies on Day 28
Time frame: Day 28
Part 2: Number of Participants With Anti-GSK3732394 Antibodies
Time frame: Up to Day 49
Part 1: Titer of Anti-drug Antibodies (ADAs) Against GSK3732394 on Day 28
Time frame: Day 28
Part 2: Titer of ADAs Against GSK3732394
Time frame: Up to Day 49
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36191080Krystal M, Chabria S, Austin D, Wolstenholme A, Wensel D, Lataillade M, Abberbock J, Baker M, Ackerman P. A Phase 1 randomized study of GSK3732394, an investigational long-acting biologic treatment regimen for HIV-1 infection. Antivir Ther. 2022 Oct;27(5):13596535221131164. doi: 10.1177/13596535221131164.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
Related trials for HIV Infections
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
ViiV Healthcare
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK3732394 in people with HIV Infections, run by ViiV Healthcare at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1: Number of Participants With Non-serious Adverse Event (SAEs) and SAEs (time frame: Up to Day 28). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03984812, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2021.