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
Part B sub study is Open Label
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
197
Syringe, Subcutaneous, 180 μg, Once Weekly, 48 weeks
Syringe, Subcutaneous 180 μg, Once Weekly, 48 Weeks
Syringe, Subcutaneous, 180 µg, Once weekly, 48 weeks
Part A: Proportion of subjects who achieve Hepatitis B e antigen (HBeAg) seroconversion
Time frame: 24 weeks post-dosing (Week 72)
Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events
Time frame: Week 24
Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events
Time frame: 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
Time frame: Up to 84 Weeks
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
Time frame: 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))
Time frame: Baseline (Day 1), Weeks 24, 48, 72, 96, 120, 144, 168 and 192
Part A: Proportion of subjects with ALT normalization (≤ 1 x ULN)
Time frame: Weeks 24, 48, 72, 96, 120, 144, 168 and 192
Part A: Hepatitis E antigen (HBeAg) loss
Time frame: Weeks 24, 48, 72, 96, 120, 144, 168 and 192
Part A: HBeAg seroconversion
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Tablet, Oral, 0.5 mg, Once daily, 12 weeks initial monotherapy followed by 48 weeks of combination therapy with PegIFN lambda
Advanced Clinical Research Institute
Anaheim, California, United States
Sc Clinical Research, Inc.
Garden Grove, California, United States
University Of California, Davis Medical Center
Sacramento, California, United States
Research And Education, Inc.
San Diego, California, United States
Yale New Haven Hospital
New Haven, Connecticut, United States
Atlanta Gastroenterology Associates, Llc
Atlanta, Georgia, United States
Mercy Medical Center
Baltimore, Maryland, United States
Gastro Center Of Maryland
Colombia, Maryland, United States
Medical Procare, Pllc
Flushing, New York, United States
Office Of Sing Chan Md
Flushing, New York, United States
...and 43 more locations
Time frame: Weeks 24, 48, 96, 120, 144, 168 and 192
Part A: Mean change from baseline in log10 quantitative HBeAg levels over time
Time frame: 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
Time frame: Up to Week 24
Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Weeks 4, 8, 12, 24, 36, 60, and 84
Part B: HBeAg loss and seroconversion in subjects treated with Lambda/ETV regimen
Time frame: Weeks 12, 24, 36, 60 and 84
Part B: HBeAg levels over time in subjects treated with Lambda/ETV regimen
Time frame: Weeks 4, 8, 12, 24, 36, 60, and 84
Part B: biochemical response rates in subjects treated with Lambda/ETV regimen
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60
Part B: Rate of resistance to ETV during treatment with the Lambda/ETV regimen
Time frame: Up to Week 84