Dose Ranging Study of Pegylated Interferon Lambda in Patients With Hepatitis B and Positive for the Hepatitis B e Antigen
Phase 2
Completed
- Conditions
- Hepatitis B Virus
- Interventions
- Registration Number
- NCT01204762
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
At least 1 dose of pegIFNλ will be identified which is safe, well tolerated, and efficacious for the treatment of chronic hepatitis B virus infection (CHB)
Amendment 7, Part B Sub Study: The primary purpose of this amendment is to obtain preliminary data on the safety of pegylated interferon Lambda (Lambda) when administered in combination with Entecavir(ETV) to patients with hepatitis E antigen-positive (HBeAg-positive) chronic hepatitis B(CHB) infection employing a sequential therapy approach
- Detailed Description
Part B sub study is Open Label
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 197
Inclusion Criteria
- Infection with the hepatitis B virus (HBV) and positive for the hepatitis B e antigen
- Between the ages of 18 and 70
- Have not been previously treated with an interferon
- HBV nucleos(t)ide-naive
Exclusion Criteria
- Not infected with the hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
- Do not have a serious liver, psychiatric, blood, thyroid, lung, heart or eye disease
- Able to tolerate oral medication
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A Arm 2: pegIFNα-2a pegIFNα-2a - Part B: pegIFN lambda + Entecavir PegIFN lambda - Part A Arm 1: pegIFN (180 μg) pegIFN - Part B: pegIFN lambda + Entecavir Entecavir -
- Primary Outcome Measures
Name Time Method Part A: Proportion of subjects who achieve Hepatitis B e antigen (HBeAg) seroconversion 24 weeks post-dosing (Week 72) Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events 24 weeks post-dosing (Week 72) Part B: Safety and tolerability of Lambda/ETV regimen as measured by the frequency of SAEs and discontinuations due to AEs Up to 84 Weeks
- Secondary Outcome Measures
Name Time Method Part A: Proportion of subjects who achieve an hepatitis B virus Deoxyribonucleic acid levels (HBV DNA) < 50 IU/mL (approximately 300 copies/mL) using the Roche COBAS® TaqMan - High Pure System (HPS) assay Weeks 24, 48, 72, 96, 120, 144, 168 and 192 Part A: Mean change from baseline in log10 HBV DNA levels over time (Proportion of subjects with Alanine amino transferase (ALT) normalization (≤ 1 x upper limit of normal (ULN)) Baseline (Day 1), Weeks 24, 48, 72, 96, 120, 144, 168 and 192 Part A: Proportion of subjects with ALT normalization (≤ 1 x ULN) Weeks 24, 48, 72, 96, 120, 144, 168 and 192 Part B: HBeAg loss and seroconversion in subjects treated with Lambda/ETV regimen Weeks 12, 24, 36, 60 and 84 Part B: HBeAg levels over time in subjects treated with Lambda/ETV regimen Weeks 4, 8, 12, 24, 36, 60, and 84 Part B: biochemical response rates in subjects treated with Lambda/ETV regimen Weeks 4, 8, 12, 24, 36, 60, and 84 Part A: Hepatitis E antigen (HBeAg) loss Weeks 24, 48, 72, 96, 120, 144, 168 and 192 Part A: HBeAg seroconversion Weeks 24, 48, 96, 120, 144, 168 and 192 Part A: Mean change from baseline in log10 quantitative HBeAg levels over time Baseline (Day 1), Weeks 24, 48, 96, 120, 144, 168 and 192 Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities Up to Week 72 Part A: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Pegylated interferon lambda (pegIFNλ) will be derived from serum concentration versus time data Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48 Part A: Pharmacokinetic (PK) parameter Time of maximum observed concentration (Tmax) of Pegylated interferon lambda (pegIFNλ) will be derived from serum concentration versus time data Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48 Part A: Pharmacokinetic (PK) parameter Trough serum concentration pre-dose (C0) of Pegylated interferon lambda (pegIFNλ) will be derived from serum concentration versus time data Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48 Part A: PK parameter serum concentration 168 hours post observed dose [Cmin] (C0 will be used as an estimate of Cmin if sample is not collected) of pegIFNλ will be derived from serum concentration versus time data Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48 Part A: PK parameter Area under the concentration-time curve in 1 dosing interval from time 0 to 168 hours post observed dose [AUC(TAU)] of pegIFNλ will be derived from serum concentration versus time data Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48 Part A: PK parameter Accumulation index (AI) ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose (only conducted if data warrant) of pegIFNλ will be derived from serum concentration versus time data Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48 Part B: HBeAg seroconversion rate at 24 weeks off treatment Week 84 Part B: Antiviral activity of Lambda/ETV regimen, as determined by the proportion of subjects who achieve an HBV DNA < 50 IU/mL (approximately 300 copies/mL) using the Roche COBAS® TaqMan - HPS assay Weeks 4, 8, 12, 24, 36, 60, and 84 Part B: Mean change from baseline in HBV DNA over time in subjects treated with Lambda/ETV Weeks 4, 8, 12, 24, 36, 60, and 84 Part B: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Lambda/ETV regimen will be derived from serum concentration versus time data Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60 Part B: Pharmacokinetic (PK) parameter Time of maximum observed concentration (Tmax) of Lambda/ETV regimen will be derived from serum concentration versus time data Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60 Part B: Pharmacokinetic (PK) parameter Trough serum concentration pre-dose (C0) of Lambda/ETV regimen will be derived from serum concentration versus time data Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60 Part B: PK parameter Area under the concentration-time curve in 1 dosing interval from time 0 to 168 hours post observed dose [AUC(TAU)] of Lambda/ETV regimen will be derived from serum concentration versus time data Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60 Part B: PK parameter serum concentration 168 hours post observed dose [Cmin] (C0 will be used as an estimate of Cmin if sample is not collected) of Lambda/ETV regimen will be derived from serum concentration versus time data Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60 Part B: PK parameter Accumulation index (AI) ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose (only conducted if data warrant) of Lambda/ETV regimen will be derived from serum concentration versus time data Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60 Part B: Rate of resistance to ETV during treatment with the Lambda/ETV regimen Up to Week 84
Trial Locations
- Locations (17)
Sc Clinical Research, Inc.
🇺🇸Garden Grove, California, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Office Of Sing Chan Md
🇺🇸Flushing, New York, United States
Advanced Clinical Research Institute
🇺🇸Anaheim, California, United States
University Of California, Davis Medical Center
🇺🇸Sacramento, California, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Local Institution
🇨🇳Taoyuan, Taiwan
Heritage Medical Research Clinic, University Of Calgary
🇨🇦Calgary, Alberta, Canada
University Of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Gastro Center Of Maryland
🇺🇸Colombia, Maryland, United States
Medical Procare, Pllc
🇺🇸Flushing, New York, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Atlanta Gastroenterology Associates, Llc
🇺🇸Atlanta, Georgia, United States
Research And Education, Inc.
🇺🇸San Diego, California, United States
Toronto Western Hospital University Health Network
🇨🇦Toronto, Ontario, Canada
Oregon Health & Science University
🇺🇸Portland, Oregon, United States