Infection, Human Immunodeficiency VirusPhase 2SIGNETNCT01231555
Dose-finding Study of GSK2248761 in Antiretroviral Therapy-Naive Subjects (SIGNET)
A Phase 2 study testing GSK2248761 100 mg once daily, GSK2248761 200 mg once daily and Efavirenz 600 mg once daily in people with Infection, Human Immunodeficiency Virus, run by ViiV Healthcare at 12 sites in 3 countries.
Trial summary
This 96 week, Phase 2b study in 150 HIV-1 infected antiretroviral (ART) naive adult subjects consists of a dose-ranging evaluation of GSK2248761 at blinded doses of 100 mg and 200 mg once daily with a control arm of open-label efavirenz (EFV) 600 mg once daily. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infection, Human Immunodeficiency Virus
- What is being tested?
- GSK2248761 100 mg once daily, GSK2248761 200 mg once daily and Efavirenz 600 mg once daily
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 12 sitesin 3 countries
- Study dates
- 18 Nov 2010to 4 Jul 2011
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infected adults greater than or equal to 18 years of age. A female is eligible to enter and participate in the study if she is (1) Non-childbearing potential, (2) Child-bearing potential, with a negative pregnancy test at screen and Day 1 and agrees to use protocol-specified methods of birth control while on study
- HIV-1 infection with a screening plasma HIV-1 RNA greater than or equal to 1000 copies/mL
- CD4+ cell count greater than or equal to 200 cells/mm3
- Antiretroviral-naive
Who cannot join
- Any pre-existing physical or mental condition (including substance abuse disorder) which, in the opinion of the Investigator, may interfere with the subject's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the subject
- Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the drug or render the subject unable to take oral medication
- Women who are currently breastfeeding
- Any evidence of an active Centers for Disease and Prevention Control (CDC) Category C disease [CDC,1993], except cutaneous Kaposi's sarcoma not requiring systemic therapy
- History of ongoing or clinically relevant hepatitis within the previous 6 months, including chronic hepatitis B virus (HBV) infection (HBsAg positive). Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not be excluded, however Investigators must carefully assess if therapy specific for HCV infection is required; subjects who are anticipated to require such therapy during the randomized portion of the study must be excluded
- History of liver cirrhosis with or without hepatitis viral co-infection
Show all 18Show fewer
- Ongoing or clinically relevant pancreatitis
- History of the following cardiac diseases: myocardial infarction, congestive heart failure, documented hypertrophic cardiomyopathy, sustained ventricular tachycardia
- Personal or known family history of prolonged QT syndrome
- History or presence of allergy or intolerance to the study drugs or their components, or a history of drug or other allergy that, in the opinion of the Principal Investigator, contraindicates their participation. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled
- Evidence of viral resistance to any antiviral drug indicative of primary transmitted resistance in a screening or historical resistance test result
- Any acute laboratory abnormality at screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound. Any verified Grade 4 laboratory abnormality at screening would exclude a subject from study participation unless the Investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the Medical Monitor
- Any of the following laboratory values at screening: (1) Creatinine clearance <50 mL/min via Cockroft-Gault method, (2) Alanine aminotransferase (ALT) greater than or equal to 5 times upper limits of normal (ULN). Subjects with ALT > 2x ULN but <5xULN may participate in the study, if in the opinion of the Investigator and GSK Medical Monitor the lab abnormality will not interfere with the study procedures or compromise subject safety, (3) Alanine aminotransferase (ALT) greater than or equal to 3xULN and bilirubin greater than or equal to 1.5xULN (with >35% direct bilirubin)
- Any clinically significant finding on screening ECG, specifically (a single repeat is allowed to determine eligibility): (1) Heart rate <45 and >100 beats per minute (bpm) (males); <50 and >100 bpm (females). Note: A heart rate from 100 to 110 bpm can be rechecked within 30 minutes to verify eligibility, (2) QRS duration > 120 msec, (3) QTc interval > 450 msec (4) Non-sustained (greater than or equal to 3 consecutive beats) or sustained ventricular tachycardia, (5) Sinus pauses > 2.5 seconds, (6) 2nd degree (Type II) or higher AV (Atrioventricular) block, (7) Evidence of WPW (Wolff- Parkinson-White) syndrome (ventricular preexcitation), (8) Pathologic Q waves (defined as Q wave > 40 msec OR depth >0.4 mV (9) Any other abnormality which in the opinion of the Investigator would interfere with the safety of the subject
- Treatment with any of the following agents within 28 days prior to screening, or has an anticipated need for these agents during the study (1) Radiation therapy or cytotoxic chemotherapeutic agents, (2) Immunomodulators (such as systemic corticosteroids, interleukins, or interferons) Note: Subjects using short-term (<7 day) steroid tapers and inhaled corticosteroids are eligible for enrollment (3) Any non-protocol-specified agent with documented activity against HIV 1 in vitro
- Treatment with an HIV-1 immunotherapeutic vaccine within 90 days prior to screening
- Receipt of an experimental drug and/or vaccine within 28 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine, whichever is longer, prior to screening
- Immunization within 28 days prior to first dose of IP
Trial locations and contacts
12 sites in 3 countries.
12 sites in 3 countries
Germany5 sites
GSK Investigational Site
Berlin, 12157
GSK Investigational Site
Frankfurt am Main, Hesse, 60311
GSK Investigational Site
Hamburg, 20146
GSK Investigational Site
Hamburg, 20246
GSK Investigational Site
Hanover, Lower Saxony, 30625
France4 sites
GSK Investigational Site
Levallois-Perret, 92300
GSK Investigational Site
Montpellier, 34295
GSK Investigational Site
Nice, 06202
GSK Investigational Site
Paris, 75018
Spain3 sites
GSK Investigational Site
Badalona, 08916
GSK Investigational Site
Barcelona, 08036
GSK Investigational Site
Marid, 28040
About this study
Official title: Phase 2b Study to Select a Once Daily Oral Dose of GSK2248761 Administered With Tenofovir/Emtricitabine or Abacavir/Lamivudine in HIV-1 Infected Antiretroviral Therapy Naive Adult Subjects
This 96 week, Phase 2b study in 150 HIV-1 infected antiretroviral (ART) naive adult subjects consists of a dose-ranging evaluation of GSK2248761 at blinded doses of 100 mg and 200 mg once daily with a control arm of open-label efavirenz (EFV) 600 mg once daily. The background ART for all 3 arms will be chosen by the Investigators and will be either abacavir/lamivudine [ABC/3TC] or tenofovir/emtricitabine [TDF/FTC] fixed dose combination (FDC) tablets. Antiviral activity, safety, PK, and development of viral resistance will be evaluated.
Read the detailed description
Study SGN113404 is a phase 2b randomized, partially blinded, multicenter, parallel group, dose-ranging study. The study will be conducted in approximately 150 HIV-1 infected ART naïve subjects. The background NRTIs to be co-administered with GSK2248761 or EFV will be selected by Investigators prior to randomization and will be either abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) fixed dose combination (FDC) tablets.
Subjects will participate in a Screening period (Day -28 to Day -1). Subjects may be re-screened once. Subjects will be randomized 1:1:1 to receive 100 mg of GSK2248761 once daily (50 subjects), 200 mg of GSK2248761 once daily (50 subjects) or 600 mg of EFV once daily (50 subjects). All three arms will be combined with either 300 mg/200 mg TDF/FTC or 600 mg/300 mg ABC/3TC, as chosen by the Investigator. The Investigators and subjects will be blinded to the dose of GSK2248761 being administered but will know whether they receive EFV or GSK2248761. The randomization will be stratified by HIV-1 viral load (VL) at screening, < 100,000 copies/mL or >/ 100,000 copies/mL as well as the choice of backbone NRTI, TDF/FTC or ABC/3TC.
This study will be enrolled in two stages. The first stage of the study will enroll approximately 30 subjects, at which time enrollment will be paused. An analysis of safety and tolerability will be reviewed by a safety review committee (SRC) once all subjects enrolled in Stage 1 reach Week 4. The SRC review will determine if the safety and tolerability profile of GSK2248761 supports the continuation of the trial and enrollment of an additional 120 subjects. All subjects will continue on study medications during this Week 4 analysis.
Additional analyses will be conducted once all subjects complete Week 4, Week 16, Week 24 and Week 48. A second review of the safety and tolerability of GSK2248761 will be performed by the SRC once all subjects reach Week 4. There will not be a pause in the study during the Week 4 analysis of all subjects.
The Week 16 and Week 24 analyses will be used respectively to select and confirm the optimal dose of GSK2248761 for continuation. This dose will be selected based on a statistical analysis of antiviral activity, safety and tolerability criteria. If, after confirmation of the optimal dose of GSK2248761 by the Week 24 analysis, both doses are considered acceptable based on efficacy, safety and PK data, then both arms will be continued through Week 48.
Beyond Week 48, those subjects who were randomized to the non-selected dose of GSK2248761 and have not met any criteria for discontinuation will be given the option to switch to the selected dose of GSK2248761 or to discontinue permanently from the study. Once they have switched to the selected dose they will be in the Open-Label phase of the study through Week 96. After Week 96, subjects receiving GSK2248761 will be given the option to continue to receive GSK2248761 until it is locally approved and commercially available, as long as they continue to derive clinical benefit without a protocol-defined reason for discontinuation.
Subjects randomized to EFV will have the option to continue to receive EFV through Week 96 unless they meet a protocol-defined reason for discontinuation. All subjects will have the option to continue TDF/FTC or ABC/3TC through Week 96. After Week 96, subjects will be expected to obtain local access to all commercially available ART.
Randomization will be stratified by:
- HIV-1 RNA < or >/ 100,000 copies/mL at screening
- Use of ABC/3TC or TDF/FTC FDC tablets as initial background ART
Switch of a background NRTI for toxicity management to an alternative marketed NRTI is allowed once. Switches of a background NRTI for any other reason are not permitted in the study. A switch of GSK2248761 or EFV is not allowed.
Study Endpoints /Assessments: Subjects will have assessments performed which will include baseline demographics, disease characteristics, and safety (laboratory and clinical evaluations). On study safety, efficacy, virologic, immunologic, and PK evaluations will be conducted.
Primary Endpoint: The proportion of subjects with HIV-1 RNA <50copies/mL at Week 16. Dose selection will be based primarily on antiviral activity and tolerability in conjunction with immunologic, safety, virologic resistance and PK measures. Data from the Week 24 analysis will be used to confirm dose selection.
ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship
- Conditions
- Infection, Human Immunodeficiency Virus
- Being tested
- GSK2248761 100 mg once daily, GSK2248761 200 mg once daily, Efavirenz 600 mg once daily
- Keywords
- antiretroviral, HAART, NNRTI, emtricitabine, Sexually Transmitted Disease, antiretroviral therapy (ART)-naive adults, Immunologic Deficiency Syndrome, tenofovir, abacavir, Retroviridae Infections, GSK2248761, lamivudine, Acquired ImmunoDeficiency Syndrome (AIDS), HIV infection, efavirenz
- Medical subject headings
- Infections, Acquired Immunodeficiency Syndrome, Sexually Transmitted Diseases, Immunologic Deficiency Syndromes, Retroviridae Infections, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2248761 100 mg once dailyDrug
1x100 mg capsule plus matching placebo
GSK2248761 200 mg once dailyDrug
2x100 mg capsules
Efavirenz 600 mg once dailyDrug
1x600mg tablet
| Study group | Role | What they receive |
|---|---|---|
| GSK2248761 100 mg once daily | Experimental | In combination with either abacavir/lamivudine FDC qd or tenofovir/emtricitabine FDC qd Receives: Drug: GSK2248761 100 mg once daily |
| GSK2248761 200 mg once daily | Experimental | In combination with either abacavir/lamivudine FDC qd or tenofovir/emtricitabine FDC qd Receives: Drug: GSK2248761 200 mg once daily |
| Efavirenz 600 mg once daily | Active comparator | In combination with either abacavir/lamivudine FDC qd or tenofovir/emtricitabine FDC qd Receives: Drug: Efavirenz 600 mg once daily |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Plasma HIV-1 RNA Below 50 Copies/mL as a Function of Viral Load
This analysis was based on the Missing, Switch or Discontinuation equals Failure (MSDF) algorithm (as codified by the FDA's "snapshot" algorithm) and was adjusted for stratification factors and stage of recruitment. Dose selection was based primarily on antiviral activity and tolerability in conjunction with immunologic, safety, virologic resistance and pharmacokinetic (PK) measures. The efficacy decision criteria was based on an observed difference of >=8% between the two GSK2248761 dosage arms.
Measured: Up to Week 16
Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)
Adverse event (AE) is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. Serious adverse event (SAE) is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above.
Measured: Up to 20 Weeks
Secondary outcomes (6)
Change From Baseline (Day 1) in Plasma HIV-1 RNA Over Period
For summaries and analyses which use HIV-1 RNA level as a continuous measure, the logarithm to base 10 of the value was used. In cases where a sample was retested, the retest value was used. Baseline was defined as the value recorded on Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Data for participants prior to switch and after the switch has been presented.
Measured: Baseline (Day 1) up to Week 16
Number of Participants With HIV Associated Conditions
HIV associated condition included recurrence of previous conditions. Centre for disease control (CDC) associated conditions and non-CDC associated conditions were planned to be monitored.
Measured: Up to 20 Weeks
Number of Participants With HIV Disease Progression
Number of participants acquiring clinical disease progression or death during the treatment period were presented. Clinical disease progression was defined as the progression from Baseline (Day 1) HIV disease status in either of these categories; CDC Category A at baseline to CDC Category B event, CDC Category A at baseline to CDC Category C event, CDC Category B at baseline to CDC Category C event, CDC Category C at baseline to new CDC Category C event, CDC Category A, B or C at baseline to death. If no change occurs, it was termed as no disease progression.
Measured: Up to 20 Weeks
Number of Participants Discontinuing the Study Drugs Due to AEs
Adverse event (AE) is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. Number of participants quitting/ prematurely discontinuing the use of study drug(s) were recorded.
Measured: Up to 20 weeks
Number of Participants With Changes in Electrocardiogram (ECG) From Baseline (Day 1) Over 16 Weeks
The QTc interval was assessed by two methods Bazzette's method (QTc[b]) and Federica's method (QTc[f]). Baseline value was recorded at Day 1. Change from Baseline is the value at indicated time point minus the Baseline value. Change from Baseline values were categorized into <30 milliseconds (msec), >=30 but <60 msec, and >=60 msec. The data has been presented for QTcB and QTcF for participants prior to switching the therapy.
Measured: Baseline (Day 1) to 16 weeks
Minimum and Maximum Plasma GSK2248761 Concentration at Week 2
Maximum observed plasma concentration and minimum observed plasma concentration of GSK2248761 was recorded on Week 2. The PK parameters were calculated by standard non-compartmental analysis according to current working practices and using WinNonlin Pro 4.1 or higher. Log transformed values have been presented.
All calculations of non-compartmental parameters were based on actual sampling times.
Measured: At Week 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2010 (estimated)
- Study start18 Nov 2010
- Primary completion4 Jul 2011
- Study completion4 Jul 2011
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 Infection, Human Immunodeficiency VirusStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- ViiV Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, ViiV Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01231555
- Sponsor's protocol ID
- 113404
- Acronym
- SIGNET
- Status last verified
- Aug 2017
- First submitted
- 14 Oct 2010
- Last updated
- 17 Nov 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep. 1992 Dec 18;41(RR-17):1-19.
PubMed 1361652
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2b Study to Select a Once Daily Oral Dose of GSK2248761 Administered With Tenofovir/Emtricitabine or Abacavir/Lamivudine in HIV-1 Infected Antiretroviral Therapy Naive Adult Subjects
- ClinicalTrials.gov ID
- NCT01231555
- Acronym / sponsor ID
- SIGNET / 113404
- Conditions
- Infection, Human Immunodeficiency Virus
- Keywords
- antiretroviral, HAART, NNRTI, emtricitabine, Sexually Transmitted Disease, antiretroviral therapy (ART)-naive adults, Immunologic Deficiency Syndrome, tenofovir
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 23 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Study start
- 18 Nov 2010 (actual)
- Primary completion
- 4 Jul 2011 (actual)
- Study completion
- 4 Jul 2011 (actual)
- First posted
- 1 Nov 2010 (estimated)
- Results
- Posted 17 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This 96 week, Phase 2b study in 150 HIV-1 infected antiretroviral (ART) naive adult subjects consists of a dose-ranging evaluation of GSK2248761 at blinded doses of 100 mg and 200 mg once daily with a control arm of open-label efavirenz (EFV) 600 mg once daily. The background ART for all 3 arms will be chosen by the Investigators and will be either abacavir/lamivudine [ABC/3TC] or tenofovir/emtricitabine [TDF/FTC] fixed dose combination (FDC) tablets. Antiviral activity, safety, PK, and development of viral resistance will be evaluated.
Detailed description
Study SGN113404 is a phase 2b randomized, partially blinded, multicenter, parallel group, dose-ranging study. The study will be conducted in approximately 150 HIV-1 infected ART naïve subjects. The background NRTIs to be co-administered with GSK2248761 or EFV will be selected by Investigators prior to randomization and will be either abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) fixed dose combination (FDC) tablets.
Subjects will participate in a Screening period (Day -28 to Day -1). Subjects may be re-screened once. Subjects will be randomized 1:1:1 to receive 100 mg of GSK2248761 once daily (50 subjects), 200 mg of GSK2248761 once daily (50 subjects) or 600 mg of EFV once daily (50 subjects). All three arms will be combined with either 300 mg/200 mg TDF/FTC or 600 mg/300 mg ABC/3TC, as chosen by the Investigator. The Investigators and subjects will be blinded to the dose of GSK2248761 being administered but will know whether they receive EFV or GSK2248761. The randomization will be stratified by HIV-1 viral load (VL) at screening, < 100,000 copies/mL or >/ 100,000 copies/mL as well as the choice of backbone NRTI, TDF/FTC or ABC/3TC.
This study will be enrolled in two stages. The first stage of the study will enroll approximately 30 subjects, at which time enrollment will be paused. An analysis of safety and tolerability will be reviewed by a safety review committee (SRC) once all subjects enrolled in Stage 1 reach Week 4. The SRC review will determine if the safety and tolerability profile of GSK2248761 supports the continuation of the trial and enrollment of an additional 120 subjects. All subjects will continue on study medications during this Week 4 analysis.
Additional analyses will be conducted once all subjects complete Week 4, Week 16, Week 24 and Week 48. A second review of the safety and tolerability of GSK2248761 will be performed by the SRC once all subjects reach Week 4. There will not be a pause in the study during the Week 4 analysis of all subjects.
The Week 16 and Week 24 analyses will be used respectively to select and confirm the optimal dose of GSK2248761 for continuation. This dose will be selected based on a statistical analysis of antiviral activity, safety and tolerability criteria. If, after confirmation of the optimal dose of GSK2248761 by the Week 24 analysis, both doses are considered acceptable based on efficacy, safety and PK data, then both arms will be continued through Week 48.
Beyond Week 48, those subjects who were randomized to the non-selected dose of GSK2248761 and have not met any criteria for discontinuation will be given the option to switch to the selected dose of GSK2248761 or to discontinue permanently from the study. Once they have switched to the selected dose they will be in the Open-Label phase of the study through Week 96. After Week 96, subjects receiving GSK2248761 will be given the option to continue to receive GSK2248761 until it is locally approved and commercially available, as long as they continue to derive clinical benefit without a protocol-defined reason for discontinuation.
Subjects randomized to EFV will have the option to continue to receive EFV through Week 96 unless they meet a protocol-defined reason for discontinuation. All subjects will have the option to continue TDF/FTC or ABC/3TC through Week 96. After Week 96, subjects will be expected to obtain local access to all commercially available ART.
Randomization will be stratified by:
- HIV-1 RNA < or >/ 100,000 copies/mL at screening
- Use of ABC/3TC or TDF/FTC FDC tablets as initial background ART
Switch of a background NRTI for toxicity management to an alternative marketed NRTI is allowed once. Switches of a background NRTI for any other reason are not permitted in the study. A switch of GSK2248761 or EFV is not allowed.
Study Endpoints /Assessments: Subjects will have assessments performed which will include baseline demographics, disease characteristics, and safety (laboratory and clinical evaluations). On study safety, efficacy, virologic, immunologic, and PK evaluations will be conducted.
Primary Endpoint: The proportion of subjects with HIV-1 RNA <50copies/mL at Week 16. Dose selection will be based primarily on antiviral activity and tolerability in conjunction with immunologic, safety, virologic resistance and PK measures. Data from the Week 24 analysis will be used to confirm dose selection.
ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| GSK2248761 100 mg once daily | Experimental | Drug: GSK2248761 100 mg once dailyIn combination with either abacavir/lamivudine FDC qd or tenofovir/emtricitabine FDC qd |
| GSK2248761 200 mg once daily | Experimental | Drug: GSK2248761 200 mg once dailyIn combination with either abacavir/lamivudine FDC qd or tenofovir/emtricitabine FDC qd |
| Efavirenz 600 mg once daily | Active comparator | Drug: Efavirenz 600 mg once dailyIn combination with either abacavir/lamivudine FDC qd or tenofovir/emtricitabine FDC qd |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- HIV-1 infected adults greater than or equal to 18 years of age. A female is eligible to enter and participate in the study if she is (1) Non-childbearing potential, (2) Child-bearing potential, with a negative pregnancy test at screen and Day 1 and agrees to use protocol-specified methods of birth control while on study
- HIV-1 infection with a screening plasma HIV-1 RNA greater than or equal to 1000 copies/mL
- CD4+ cell count greater than or equal to 200 cells/mm3
- Antiretroviral-naive
Key exclusion criteria (18 listed)
- Any pre-existing physical or mental condition (including substance abuse disorder) which, in the opinion of the Investigator, may interfere with the subject's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the subject
- Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the drug or render the subject unable to take oral medication
- Women who are currently breastfeeding
- Any evidence of an active Centers for Disease and Prevention Control (CDC) Category C disease [CDC,1993], except cutaneous Kaposi's sarcoma not requiring systemic therapy
- History of ongoing or clinically relevant hepatitis within the previous 6 months, including chronic hepatitis B virus (HBV) infection (HBsAg positive). Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not be excluded, however Investigators must carefully assess if therapy specific for HCV infection is required; subjects who are anticipated to require such therapy during the randomized portion of the study must be excluded
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 |
|---|---|---|
| GSK2248761 100 mg once daily1x100 mg capsule plus matching placebo | Drug | GSK2248761 100 mg once daily |
| GSK2248761 200 mg once daily2x100 mg capsules | Drug | GSK2248761 200 mg once daily |
| Efavirenz 600 mg once daily1x600mg tablet | Drug | Efavirenz 600 mg once daily |
Primary outcome
Number of Participants With Plasma HIV-1 RNA Below 50 Copies/mL as a Function of Viral Load
Time frame: Up to Week 16
This analysis was based on the Missing, Switch or Discontinuation equals Failure (MSDF) algorithm (as codified by the FDA's "snapshot" algorithm) and was adjusted for stratification factors and stage of recruitment. Dose selection was based primarily on antiviral activity and tolerability in conjunction with immunologic, safety, virologic resistance and pharmacokinetic (PK) measures. The efficacy decision criteria was based on an observed difference of >=8% between the two GSK2248761 dosage arms.
Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)
Time frame: Up to 20 Weeks
Adverse event (AE) is an unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain time period after the study has ended. This change may or may not be caused by the intervention being studied. Serious adverse event (SAE) is an adverse event that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect. Medical events that do not result in death, are not life-threatening, or do not require hospitalization may be considered serious adverse events if they put the participant in danger or require medical or surgical intervention to prevent one of the results listed above.
6 secondary outcomes
Change From Baseline (Day 1) in Plasma HIV-1 RNA Over Period
Time frame: Baseline (Day 1) up to Week 16
Number of Participants With HIV Associated Conditions
Time frame: Up to 20 Weeks
Number of Participants With HIV Disease Progression
Time frame: Up to 20 Weeks
Number of Participants Discontinuing the Study Drugs Due to AEs
Time frame: Up to 20 weeks
Number of Participants With Changes in Electrocardiogram (ECG) From Baseline (Day 1) Over 16 Weeks
Time frame: Baseline (Day 1) to 16 weeks
Minimum and Maximum Plasma GSK2248761 Concentration at Week 2
Time frame: At Week 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 13616521993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep. 1992 Dec 18;41(RR-17):1-19.
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People Who Use Opioids/People With Opioid Use Disorder (OUD)
Enrolling by invitation
Promoting Aging and Thriving With HIV
HIV (Human Immunodeficiency Virus), Geriatric
RecruitingObservational study
Cohort of Women Living With HIV-1 and Receiving Bictegravir/Emtricitabine/Tenofovir Alafenamide
HIV (Human Immunodeficiency Virus), Pregnancy
Not yet recruiting
HIV/STI/HCV Testing and Overdose Prevention Among Survivors of Sex Trafficking
HIV Testing, STI
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
12 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK2248761 100 mg once daily, GSK2248761 200 mg once daily and Efavirenz 600 mg once daily in people with Infection, Human Immunodeficiency Virus, run by ViiV Healthcare at 12 sites in 3 countries.
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 4 inclusion and 18 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 17 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Germany, France, Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 17 Nov 2017). 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?
Number of Participants With Plasma HIV-1 RNA Below 50 Copies/mL as a Function of Viral Load (time frame: Up to Week 16). The study lists 2 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 NCT01231555, 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 17 Nov 2017.