Phase 2
Completed N=16
Safety, Antiviral Activity, and Pharmacokinetics of GSK2336805 With Peginterferon and Ribavirin in Chronic Hepatitis C Subjects
Hepatitis C, Chronic
Source: ClinicalTrials.gov NCT01439373 ↗
Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Dec 2017
Primary outcomePrimary: Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis — 3; 3; 8; 1 Participants
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participant Achieving Rapid Virological Response (RVR) at Day 28, Nominal Analysis |
3; 3; 8; 1 | — |
| PRIMARY Number of Participant Achieving RVR at Day 28, (Primary and Supportive Analyses) |
7; 1; 4; 3 | — |
| PRIMARY Probability of Participants With HCV Genotype 1 Achieving RVR At Day 28, Nominal Analysis |
0.67; 0.21 | — |
| PRIMARY Probability of Participants With HCV Genotype 1 Achieving RVR at Day 28, Primary and Supportive Analyses |
0.62; 0.21 | — |
| PRIMARY Number of Participants With HCV Genotype 1 With Virologic Response |
1; 0; 1; 0; 9; 4 | — |
| PRIMARY Change From Baseline in HCV Viral Load During 24 Hour (h) Following a Single Dose of GSK2336805 on the Log 10 Scale |
0.02; -0.01; -0.03; -0.00; -0.70; -0.07 | — |
| PRIMARY Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Event (SAE) During Treatment Period |
11; 4; 0; 0 | — |
| PRIMARY Change From Baseline in QTcF Interval at Day 2 and 28 |
0.01; 0.82; -5.15; 9.13 | — |
| SECONDARY Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade Hematology Parameters for Day 1 to Day 28 |
7; 3; 3; 1; 1; 0 | — |
| SECONDARY Number of Participants With Shift From Baseline to Worst Post Baseline Toxicity Grade for Serum Chemistry Parameters for Day 1 to Day 28 |
11; 2; 0; 1; 11; 3 | — |
| SECONDARY Number of Participants With Shifts in Urinalysis Parameters From Normal at Baseline to Abnormal |
0; 1; 0; 1; 1; 2 | — |
| SECONDARY Number of Participants With Vital Signs of Potential Clinical Concern |
0; 0 | — |
| SECONDARY Mean Serum HCV RNA Levels at Baseline (Day 1), Day 2 and Day 28 |
6.61; 5.43; 4.23; 5.33; 1.80; 3.44 | — |
| SECONDARY Mean Change From Baseline in Serum HCV RNA Levels at Day 2 and Day 28 |
-2.38; -0.11; -4.78; -1.99 | — |
| SECONDARY Change From Baseline in Serum Alanine Aminotransferase Levels |
-15.3; -15.0; -25.7; -0.5; -25.9; -10.0 | — |
| SECONDARY Median Serum Alanine Aminotransferase at Baseline, Day 7, 14, 21, 28 and 42 |
56.0; 43.5; 41.5; 37.0; 28.0; 48.5 | — |
| SECONDARY 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 |
2977.79; 3284.90 | — |
| SECONDARY Median Time of Maximal Plasma Concentration (Tmax) of GSK2336805 and Lag Time Before First Observation of Quantifiable Concentration (Tlag) at Day 1 |
2.00; 0.00 | — |
| SECONDARY Mean Maximum Plasma Concentration of GSK2336805 (Cmax) and Concentration at 24 h (C24) at Day 1 |
404.84; 26.98 | — |
| SECONDARY Mean Apparent Clearance (CL/F) of GSK2336805 |
18.27 | — |
| SECONDARY Mean Pre-dose Concentration and Concentration at 2 to 4 h Post-dose of GSK2336805 at Days 7, 14, 21, and 28 |
37.80; 621.40; 314.19; 121.57; 518.82; 364.75 | — |
Eligibility Criteria
Key Inclusion Criteria
- 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
Key Exclusion Criteria
- 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
- 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
Data sourced from ClinicalTrials.gov (NCT01439373). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.