Hepatitis B Virus
Conditions
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
Interventions
DRUGpegIFN
Syringe, Subcutaneous, 180 μg, Once Weekly, 48 weeks
DRUGpegIFNα-2a
Syringe, Subcutaneous 180 μg, Once Weekly, 48 Weeks
DRUGPegIFN lambda
Syringe, Subcutaneous, 180 µg, Once weekly, 48 weeks
DRUGEntecavir
Tablet, Oral, 0.5 mg, Once daily, 12 weeks initial monotherapy followed by 48 weeks of combination therapy with PegIFN lambda
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 | Week 24 |
| 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
| Measure | Time frame |
|---|---|
| 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 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 24 |
| 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 B: biochemical response rates in subjects treated with Lambda/ETV regimen | Weeks 4, 8, 12, 24, 36, 60, and 84 |
| Part B: HBeAg loss and seroconversion in subjects treated with Lambda/ETV regimen | Weeks 12, 24, 36, 60 and 84 |
| 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 |
| 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 B: HBeAg levels over time in subjects treated with Lambda/ETV regimen | Weeks 4, 8, 12, 24, 36, 60, and 84 |
| 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 |
Countries
Australia, Canada, France, Germany, Hong Kong, Italy, Netherlands, Singapore, South Korea, Taiwan, United States
Outcome results
None listed