Hepatitis C, ChronicPhase 2NCT01439373
Safety, Antiviral Activity, and Pharmacokinetics of GSK2336805 With Peginterferon and Ribavirin in Chronic Hepatitis C Subjects
A Phase 2 study testing GSK2336805, Pegylated interferon alfa-2a and Ribavirin in people with Hepatitis C, Chronic, run by GlaxoSmithKline at 10 sites in 2 countries.
Trial summary
GSK2336805 is a hepatitis C virus (HCV) NS5A inhibitor being developed for the treatment of chronic hepatitis C (CHC). This study will assess the safety, antiviral activity, and pharmacokinetics of GSK2336805 alone and in combination with peginterferon alfa 2a and ribavirin in subjects with chronic hepatitis C (CHC). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis C, Chronic
- What is being tested?
- GSK2336805, Pegylated interferon alfa-2a and Ribavirin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 7 Jul 2011to 5 Dec 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documented chronic genotype 1 or genotype 4 HCV infection
- Naïve to all HCV antiviral treatment(s)
- Agree to IL28B genotyping
- A body mass index >18 kg/m2 but not exceeding 36 kg/m2
- Liver biopsy obtained within 3 years (36 calendar months) prior to the Day 1 visit, with a fibrosis classification of non-cirrhotic. If no recent (<36 months) liver biopsy is available, a study qualifying biopsy must be performed prior to Baseline (Day 1)
- All fertile males and females must use two forms of effective contraception between them during treatment and during the 24 weeks after treatment ends
- Otherwise healthy as determined by the medical history, physical examination, ECG findings, and clinical laboratory measurements performed at Screening
Who cannot join
- Positive test at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody
- History of any other clinically significant chronic liver disease
- History of ascites, variceal hemorrhage, hepatic encephalopathy, or conditions consistent with decompensated liver disease
- Positive results on urine screen for drugs of abuse test at Screening (unless used as medical treatment, e.g., with a prescription)
- History of alcohol/drug abuse or dependence within 6 months of the study start (unless participating in a controlled rehabilitation program)
- Screening ECG corrected QT interval value greater than 450 ms and/or clinically significant ECG findings
Show all 15Show fewer
- A personal or family history of Torsade de Pointes findings
- Pregnant or nursing women
- Males with a female partner who is pregnant
- Abnormal hematological and biochemical parameters as specified in the protocol
- History of major organ transplantation with an existing functional graft
- Thyroid dysfunction not adequately controlled
- Subjects with a history of suicide attempt or hospitalization for depression in the past 5 years and/or any current (within 6 months) severe or poorly controlled psychiatric disorder
- History or current evidence of immunologic disorder; pulmonary, cardiac, or pulmonary disease; seizure disorder; cancer or history of malignancy that in the opinion of the investigator makes the subject unsuitable for the study
- Participation in a clinical study with an investigational drug, biologic, or device within 3 months prior to first dose administration
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States9 sites
GSK Investigational Site
Anaheim, California, 92801
GSK Investigational Site
Chula Vista, California, 91911
GSK Investigational Site
Coronado, California, 92118
GSK Investigational Site
Houston, Texas, 77004
GSK Investigational Site
La Mesa, California, 91942
GSK Investigational Site
Las Vegas, Nevada, 89109
GSK Investigational Site
Miramar, Florida, 33025
GSK Investigational Site
Oceanside, California, 92056
GSK Investigational Site
Tulsa, Oklahoma, 74104
About this study
Official title: Double-Blind, Randomized, Placebo-Controlled Study to Assess Safety, Efficacy, and Pharmacokinetics (PK) of GSK2336805 in Combination With Peginterferon and Ribavirin in Treatment-naive Chronic Hepatitis C Subjects With Hepatitis C Virus Genotypes 1 or 4
GSK2336805 is a hepatitis C virus (HCV) NS5A inhibitor being developed for the treatment of chronic hepatitis C (CHC). This study will assess the safety, antiviral activity, and pharmacokinetics of GSK2336805 alone and in combination with peginterferon alfa 2a and ribavirin in subjects with chronic hepatitis C (CHC).
Read the detailed description
HCV infection is a major public health problem globally and a leading cause of chronic liver disease. New medications are needed that are better tolerated and offer a greater chance of achieving sustained viral clearance compared to currently available therapy. GSK2336805 is a HCV NS5A inhibitor being developed for the treatment of subjects with CHC. This Phase II, double blind, randomized, placebo-controlled study will assess the safety, antiviral activity, and pharmacokinetics of GSK2336805 alone and in combination with peginterferon alfa 2a and ribavirin in subjects with CHC. Subjects will be randomly allocated on a 2:1 basis to GSK2336805 or matching placebo and will be stratified by IL28B status and HCV viral genotype (genotype 1 or 4). The study consists of 2 parts. In Part 1, GSK2336805 or matching placebo will be given as single-dose monotherapy (Day 1). In Part 2, GSK2336805 or matching placebo will be co-administered with peginterferon alfa-2a and ribavirin through 4 weeks of treatment (Days 2 to 28). After completion of Part 2, GSK2336805/matching placebo will be discontinued and subjects will be offered continued standard-of-care anti-HCV therapy.
- Conditions
- Hepatitis C, Chronic
- Being tested
- GSK2336805, Pegylated interferon alfa-2a, Ribavirin, GSK2336805 Matching Placebo
- Keywords
- chronic hepatitis C, NS5A inhibitor, ribavirin, pegylated interferon, GSK2336805
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2336805Drug
Active Investigational Drug
Pegylated interferon alfa-2aDrug
Also called Pegasys
Standard of Care drug
RibavirinDrug
Standard of Care drug
GSK2336805 Matching PlaceboDrug
Also called Placebo
Placebo of Investigational Drug
| Study group | Role | What they receive |
|---|---|---|
| GSK2336805 | Experimental | Study Part 1 Receives: Drug: GSK2336805 |
| Placebo | Placebo comparator | Study Part 1 Receives: Drug: GSK2336805 Matching Placebo |
| GSK2336805 + pegylated interferon alfa-2a + ribavrin | Experimental | Study Part 2 Receives: Drug: GSK2336805; Drug: Pegylated interferon alfa-2a; Drug: Ribavirin |
| Placebo + pegylated interferon alfa-2a + ribavirin | Active comparator | Study Part 2 Receives: Drug: Pegylated interferon alfa-2a; Drug: Ribavirin; Drug: GSK2336805 Matching Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis
RVR was defined as the proportion of participants below the assay lower limit of detection (LOD) <18 International units per milliliter (IU/mL) for Hepatitis C virus (HCV) ribonucleic acid (RNA) after 4 weeks of treatment (Day 28). Participants achieving RVR at Day 28 were considered treatment responders. Participants with missing HCV RNA values at Day 28 or discontinued before Day 28 were considered as treatment failure . Proportion of participants with HCV genotype 1 achieving RVR was the primary comparison of interest to show superiority of GSK2336805 over placebo in genotype 1 participants.
Measured: Day 28
Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses)
RVR was defined as the proportion of participants LOD <18 IU/mL for HCV RNA after 4 weeks of treatment (Day 28). Participants achieving RVR at Day 28 were considered treatment responders. Participants with missing HCV RNA values at Day 28 or discontinued before Day 28 were considered as treatment failure. Proportion of participants with HCV genotype 1 achieving RVR was the primary comparison of interest to show superiority of GSK2336805 over placebo in genotype 1 participants. The primary and supportive analysis differs from the nominal analysis as supportive analysis is assessed at Day 28 ± 2 (2 days visit window) whereas, the nominal analysis was assessed at Day 28.
Measured: Day 28
Probability of Participants With HCV Genotype 1 Achieving RVR At Day 28, Nominal Analysis
The primary comparison of interest was performed using a Bayesian probability model. Probability of achieving undetectable HCV RNA distribution analyzed by nominal analysis was reported.
Measured: Day 28
Probability of Participants With HCV Genotype 1 Achieving RVR at Day 28, Primary and Supportive Analyses
The primary comparison of interest was performed using a Bayesian probability model. Probability of achieving undetectable HCV RNA distribution analyzed was reported.
Measured: Day 28
Number of Participants With HCV Genotype 1 With Virologic Response
Serum for determination of HCV genotype was collected at the screening visit. Genotype was determined by the VERSANT HCV genotype 2.0 Assay (LiPA). Number of participants with HCV genotype 1 were reported.
Measured: Day 7, 14 and 21
Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale
Blood samples for determination of HCV RNA levels were collected at immediately prior to and 1, 2, 4, 6, and 8 and 24 h after the first dose in Part 1 (Day 1). Measurement of HCV viral load was analyzed by the central laboratory using the COBAS AmpliPrep/COBAS TaqMan HCV test. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. Change from Baseline was computed as value at post Baseline specified time point minus Baseline value. Virus RNA levels reported as <43 are undetectable levels. If the result for HCV RNA (IU/ML) was <43, then change from Baseline was calculated using 42, and the change from Baseline on the log scale was calculated using log (42).
Measured: Day 1 (Baseline [Pre-dose], 1, 2, 4, 6, and 8 and 24 h)
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period
AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Measured: Up to Day 28
Change From Baseline in QTcF Interval at Day 2 and 28
Single 12-lead electrocardiogram (ECG) was obtained. The standard ECG criteria of potential clinical importance were 1) absolute QTc Interval, > 450 milliseconds (msec), 2) absolute PR Interval, <110 msec, 3) absolute QRS Interval, < 75 msec and 4) increase from baseline in QTc > 60 msec. QTc Interval was calculated using Frederica correction formula: QTcF = QT / (RR)^1/3. Change from Baseline was calculated by subtracting the Baseline assessment value from post Baseline visit value. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. The change from Baseline in QTc Interval at Day 2 and 28 were reported.
Measured: Baseline (Day 1, Pre-dose ), Day 2 and Day 28
Secondary outcomes (13)
Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28
Laboratory abnormalities were graded according to the modified division of AIDS ( DAIDS）version 1.0. Shift from Baseline to worst post baseline toxicity grade (where applicable) were presented for Day 1 to Day 28. The toxicity Grades were, Grade 1: mild (no or minimal interference with usual social \& functional activities); Grade 2: moderate (greater than minimal interference with usual social and functional activities); Grade 3: severe (inability to perform usual social and functional activities); Grade 4: potentially life threatening (inability to perform basic self-care functions or Medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death). Hematology parameters were red blood cell, hemoglobin, hematocrit, platelet white blood cell count with differential leukocyte count, mean corpuscular volume, prothrombin time and international normalized ratio.
Measured: Baseline (Day 1) to Day 28
Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28
Abnormalities were graded according to the modified DAIDS version 1.0. Shift from Baseline to worst post Baseline toxicity grade were presented for Day 1 to Day 28. The toxicity Grades were, Grade 1: mild (no or minimal interference with usual social \& functional activities); Grade 2: moderate (greater than minimal interference with usual social and functional activities); Grade 3: severe (inability to perform usual social and functional activities); Grade 4: potentially life threatening (inability to perform basic self-care functions or Medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death). Clinical chemistry parameters were alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatine phosphokinase, total CO2, chloride, creatinine, glucose, sodium, phosphate, potassium, total albumin, total bilirubin, and direct bilirubin. Only participants with change in toxicity grades are reported.
Measured: Baseline (Day 1) and 28
Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal
The urinalysis parameters analyzed were Leukocyte esterase, bilirubin, occult blood, glucose, ketones, nitrite, pH, specific gravity and dipstick assessments. Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important urinalysis findings at specified visit were reported. Visits where no abnormal values were observed not reported.
Measured: Day 14, 28, Follow-up (Day 42)
Number of Participants With Vital Signs of Potential Clinical Concern
The potential clinical importance ranges (low and high) of the vital sign parameters were for systolic blood pressure (<85 and >160 millimeter of mercury [mmHg]), diastolic blood pressure (<45 and >100 mmHg) and heart rate (<40 and >110 beats per minute). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important vital parameter findings at any visit were reported.
Measured: Up to 42 days
Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28
Blood samples for determination of HCV RNA levels were collected from screening, immediately prior to and 1, 2, 4, 6, and 8 h after the first dose in Part 1 (Day 1), during Part 2 on Days 2 (24 h after the Day 1 dose), 7, 14, 21, and 28, and at the post-treatment follow-up visit on Day 42. All viral load samples, with the exception of the one taken during the screening visit, were taken in duplicate. The actual time and date of each sample collection will be recorded. Measurement of HCV viral load was analyzed by the central laboratory using the COBAS AmpliPrep/COBAS TaqMan HCV test.
Measured: Baseline (Day 1, pre-dose), Day 2 (24 h, Post-dose) and Day 28
Mean Change From Baseline in Serum HCV RNA Levels at Day 2 and Day 28
Blood samples for determination of HCV RNA levels were collected from screening, immediately prior to and 1, 2, 4, 6, and 8 h after the first dose in Part 1 (Day 1), during Part 2 on Days 2 (24 h after the Day 1 dose), 7, 14, 21, and 28, and at the post-treatment follow-up visit on Day 42. All viral load samples, with the exception of the one taken during the screening visit, were taken in duplicate. The actual time and date of each sample collection will be recorded. Measurement of HCV viral load was analyzed by the central laboratory using the COBAS AmpliPrep/COBAS TaqMan HCV test.
Measured: Baseline (Day 1, Pre -dose ) and Day 2 (24 h, post-dose), Day 28
Change From Baseline in Serum Alanine Aminotransferase Levels
Blood samples were collected at Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42 for determination of serum alanine aminotransferase levels. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. Change from Baseline was computed as value at post Baseline specified time point minus Baseline value.
Measured: Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42
Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42
Blood samples were collected at Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42 for determination of serum alanine aminotransferase levels.
Measured: Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42
Mean Area Under the Concentration-time Curve (AUC[0-24]), AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) of GSK2336805, at Day 1
AUC values were determined using the linear-up, log-down trapezoidal rule. The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were below quantification limit (BLQ) before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters.
Measured: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 2)
Median Time of Maximal Plasma Concentration (Tmax) of GSK2336805 and Lag Time Before First Observation of Quantifiable Concentration (Tlag) at Day 1
The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters
Measured: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 2)
Mean Maximum Plasma Concentration of GSK2336805 (Cmax) and Concentration at 24 h (C24) at Day 1
The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by non-compartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters.
Measured: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1)
Mean Apparent Clearance (CL/F) of GSK2336805
The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters
Measured: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1)
Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28
The individual plasma concentration and actual time data was used to derive the PK parameters of GSK2336805 on Day 1 by noncompartmental PK analyses. For the calculation of PK parameters all plasma concentrations that were BLQ before the first measurable concentration were set to zero. The BLQ values that occur at the end of the profile after the last quantifiable concentration were set to missing. Actual sampling times, rather than scheduled sampling times, were used in all computations of PK parameters.
Measured: 0 (pre-dose), 0 to 2 h, > 2 h up to 4 h, > 4 h up to 6 h, or > 6 h up to 10 h on Days 7, 14, 21 and 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2011 (estimated)
- Study start7 Jul 2011
- Primary completion5 Dec 2011
- Study completion5 Dec 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 Hepatitis C, ChronicStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PPD Development, LP
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01439373
- Sponsor's protocol ID
- 115519
- Status last verified
- Nov 2017
- First submitted
- 7 Jul 2011
- Last updated
- 11 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Gardner S, Cutrell A, Elko-Simms C, Adkison K, Hamatake R, Walker J, Rodriguez-Torres M, Hong Z. A double-blind, randomized, placebo-controlled study to assess the safety, antiviral activity and pharmacokinetics of GSK2336805 when given as monotherapy and in combination with peginterferon alfa-2a and ribavirin in hepatitis C virus genotype 1-infected treatment-naive subjects. Liver Int. 2014 Jul;34(6):e89-95. doi: 10.1111/liv.12334. Epub 2013 Oct 16.
PubMed 24107072
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-Blind, Randomized, Placebo-Controlled Study to Assess Safety, Efficacy, and Pharmacokinetics (PK) of GSK2336805 in Combination With Peginterferon and Ribavirin in Treatment-naive Chronic Hepatitis C Subjects With Hepatitis C Virus Genotypes 1 or 4
- ClinicalTrials.gov ID
- NCT01439373
- Acronym / sponsor ID
- 115519
- Conditions
- Hepatitis C, Chronic
- Keywords
- chronic hepatitis C, NS5A inhibitor, ribavirin, pegylated interferon, GSK2336805
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Collaborators
- PPD Development, LP
- Study start
- 7 Jul 2011 (actual)
- Primary completion
- 5 Dec 2011 (actual)
- Study completion
- 5 Dec 2011 (actual)
- First posted
- 23 Sep 2011 (estimated)
- Results
- Posted 11 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
GSK2336805 is a hepatitis C virus (HCV) NS5A inhibitor being developed for the treatment of chronic hepatitis C (CHC). This study will assess the safety, antiviral activity, and pharmacokinetics of GSK2336805 alone and in combination with peginterferon alfa 2a and ribavirin in subjects with chronic hepatitis C (CHC).
Detailed description
HCV infection is a major public health problem globally and a leading cause of chronic liver disease. New medications are needed that are better tolerated and offer a greater chance of achieving sustained viral clearance compared to currently available therapy. GSK2336805 is a HCV NS5A inhibitor being developed for the treatment of subjects with CHC. This Phase II, double blind, randomized, placebo-controlled study will assess the safety, antiviral activity, and pharmacokinetics of GSK2336805 alone and in combination with peginterferon alfa 2a and ribavirin in subjects with CHC. Subjects will be randomly allocated on a 2:1 basis to GSK2336805 or matching placebo and will be stratified by IL28B status and HCV viral genotype (genotype 1 or 4). The study consists of 2 parts. In Part 1, GSK2336805 or matching placebo will be given as single-dose monotherapy (Day 1). In Part 2, GSK2336805 or matching placebo will be co-administered with peginterferon alfa-2a and ribavirin through 4 weeks of treatment (Days 2 to 28). After completion of Part 2, GSK2336805/matching placebo will be discontinued and subjects will be offered continued standard-of-care anti-HCV therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| GSK2336805 | Experimental | Drug: GSK2336805Study Part 1 |
| Placebo | Placebo comparator | Drug: GSK2336805 Matching PlaceboStudy Part 1 |
| GSK2336805 + pegylated interferon alfa-2a + ribavrin | Experimental | Drug: GSK2336805, Drug: Pegylated interferon alfa-2a, Drug: RibavirinStudy Part 2 |
| Placebo + pegylated interferon alfa-2a + ribavirin | Active comparator | Drug: Pegylated interferon alfa-2a, Drug: Ribavirin, Drug: GSK2336805 Matching PlaceboStudy Part 2 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Documented chronic genotype 1 or genotype 4 HCV infection
- Naïve to all HCV antiviral treatment(s)
- Agree to IL28B genotyping
- A body mass index >18 kg/m2 but not exceeding 36 kg/m2
- Liver biopsy obtained within 3 years (36 calendar months) prior to the Day 1 visit, with a fibrosis classification of non-cirrhotic. If no recent (<36 months) liver biopsy is available, a study qualifying biopsy must be performed prior to Baseline (Day 1)
Key exclusion criteria (15 listed)
- Positive test at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody
- History of any other clinically significant chronic liver disease
- History of ascites, variceal hemorrhage, hepatic encephalopathy, or conditions consistent with decompensated liver disease
- Positive results on urine screen for drugs of abuse test at Screening (unless used as medical treatment, e.g., with a prescription)
- History of alcohol/drug abuse or dependence within 6 months of the study start (unless participating in a controlled rehabilitation program)
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 |
|---|---|---|
| GSK2336805Active Investigational Drug | Drug | GSK2336805, GSK2336805 + pegylated interferon alfa-2a + ribavrin |
| Pegylated interferon alfa-2aAlso: PegasysStandard of Care drug | Drug | GSK2336805 + pegylated interferon alfa-2a + ribavrin, Placebo + pegylated interferon alfa-2a + ribavirin |
| RibavirinStandard of Care drug | Drug | GSK2336805 + pegylated interferon alfa-2a + ribavrin, Placebo + pegylated interferon alfa-2a + ribavirin |
| GSK2336805 Matching PlaceboAlso: PlaceboPlacebo of Investigational Drug | Drug | Placebo, Placebo + pegylated interferon alfa-2a + ribavirin |
Primary outcome
Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis
Time frame: Day 28
RVR was defined as the proportion of participants below the assay lower limit of detection (LOD) <18 International units per milliliter (IU/mL) for Hepatitis C virus (HCV) ribonucleic acid (RNA) after 4 weeks of treatment (Day 28). Participants achieving RVR at Day 28 were considered treatment responders. Participants with missing HCV RNA values at Day 28 or discontinued before Day 28 were considered as treatment failure . Proportion of participants with HCV genotype 1 achieving RVR was the primary comparison of interest to show superiority of GSK2336805 over placebo in genotype 1 participants.
Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses)
Time frame: Day 28
RVR was defined as the proportion of participants LOD <18 IU/mL for HCV RNA after 4 weeks of treatment (Day 28). Participants achieving RVR at Day 28 were considered treatment responders. Participants with missing HCV RNA values at Day 28 or discontinued before Day 28 were considered as treatment failure. Proportion of participants with HCV genotype 1 achieving RVR was the primary comparison of interest to show superiority of GSK2336805 over placebo in genotype 1 participants. The primary and supportive analysis differs from the nominal analysis as supportive analysis is assessed at Day 28 ± 2 (2 days visit window) whereas, the nominal analysis was assessed at Day 28.
Probability of Participants With HCV Genotype 1 Achieving RVR At Day 28, Nominal Analysis
Time frame: Day 28
The primary comparison of interest was performed using a Bayesian probability model. Probability of achieving undetectable HCV RNA distribution analyzed by nominal analysis was reported.
Probability of Participants With HCV Genotype 1 Achieving RVR at Day 28, Primary and Supportive Analyses
Time frame: Day 28
The primary comparison of interest was performed using a Bayesian probability model. Probability of achieving undetectable HCV RNA distribution analyzed was reported.
Number of Participants With HCV Genotype 1 With Virologic Response
Time frame: Day 7, 14 and 21
Serum for determination of HCV genotype was collected at the screening visit. Genotype was determined by the VERSANT HCV genotype 2.0 Assay (LiPA). Number of participants with HCV genotype 1 were reported.
Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale
Time frame: Day 1 (Baseline [Pre-dose], 1, 2, 4, 6, and 8 and 24 h)
Blood samples for determination of HCV RNA levels were collected at immediately prior to and 1, 2, 4, 6, and 8 and 24 h after the first dose in Part 1 (Day 1). Measurement of HCV viral load was analyzed by the central laboratory using the COBAS AmpliPrep/COBAS TaqMan HCV test. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. Change from Baseline was computed as value at post Baseline specified time point minus Baseline value. Virus RNA levels reported as <43 are undetectable levels. If the result for HCV RNA (IU/ML) was <43, then change from Baseline was calculated using 42, and the change from Baseline on the log scale was calculated using log (42).
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period
Time frame: Up to Day 28
AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE include AEs those result in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Change From Baseline in QTcF Interval at Day 2 and 28
Time frame: Baseline (Day 1, Pre-dose ), Day 2 and Day 28
Single 12-lead electrocardiogram (ECG) was obtained. The standard ECG criteria of potential clinical importance were 1) absolute QTc Interval, > 450 milliseconds (msec), 2) absolute PR Interval, <110 msec, 3) absolute QRS Interval, < 75 msec and 4) increase from baseline in QTc > 60 msec. QTc Interval was calculated using Frederica correction formula: QTcF = QT / (RR)^1/3. Change from Baseline was calculated by subtracting the Baseline assessment value from post Baseline visit value. Baseline was defined as the last non-missing assessment on or before the first dose of study drug. The change from Baseline in QTc Interval at Day 2 and 28 were reported.
13 secondary outcomes
Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28
Time frame: Baseline (Day 1) to Day 28
Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28
Time frame: Baseline (Day 1) and 28
Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal
Time frame: Day 14, 28, Follow-up (Day 42)
Number of Participants With Vital Signs of Potential Clinical Concern
Time frame: Up to 42 days
Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28
Time frame: Baseline (Day 1, pre-dose), Day 2 (24 h, Post-dose) and Day 28
Mean Change From Baseline in Serum HCV RNA Levels at Day 2 and Day 28
Time frame: Baseline (Day 1, Pre -dose ) and Day 2 (24 h, post-dose), Day 28
Change From Baseline in Serum Alanine Aminotransferase Levels
Time frame: Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42
Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42
Time frame: Baseline (Day 1, Pre-dose), Day 7, 14, 21, 28 and 42
Mean Area Under the Concentration-time Curve (AUC[0-24]), AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) of GSK2336805, at Day 1
Time frame: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 2)
Median Time of Maximal Plasma Concentration (Tmax) of GSK2336805 and Lag Time Before First Observation of Quantifiable Concentration (Tlag) at Day 1
Time frame: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 2)
Mean Maximum Plasma Concentration of GSK2336805 (Cmax) and Concentration at 24 h (C24) at Day 1
Time frame: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1)
Mean Apparent Clearance (CL/F) of GSK2336805
Time frame: 0.0 (pre-dose) and 1, 2, 4, 6, 8, and 24 h post-dose (morning of Day 1)
Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28
Time frame: 0 (pre-dose), 0 to 2 h, > 2 h up to 4 h, > 4 h up to 6 h, or > 6 h up to 10 h on Days 7, 14, 21 and 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24107072Gardner S, Cutrell A, Elko-Simms C, Adkison K, Hamatake R, Walker J, Rodriguez-Torres M, Hong Z. A double-blind, randomized, placebo-controlled study to assess the safety, antiviral activity and pharmacokinetics of GSK2336805 when given as monotherapy and in combination with peginterferon alfa-2a and ribavirin in hepatitis C virus genotype 1-infected treatment-naive subjects. Liver Int. 2014 Jul;34(6):e89-95. doi: 10.1111/liv.12334. Epub 2013 Oct 16.
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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
GlaxoSmithKline
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK2336805, Pegylated interferon alfa-2a and Ribavirin in people with Hepatitis C, Chronic, run by GlaxoSmithKline at 10 sites in 2 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 7 inclusion and 15 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: finished, as of the sponsor's last update on 11 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Puerto Rico. 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. Some participants in this study may receive a placebo. 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 11 Dec 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 Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis (time frame: Day 28). The study lists 8 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 NCT01439373, 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 11 Dec 2017.