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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-020387-38 | EudraCT Number |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A Arm 1: pegIFN (180 μg) | Experimental |
| |
| Part A Arm 2: pegIFNα-2a | Active Comparator |
| |
| Part B: pegIFN lambda + Entecavir | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| pegIFN | Drug | Syringe, Subcutaneous, 180 μg, Once Weekly, 48 weeks |
| |
| Measure | Description | 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 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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)) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Advanced Clinical Research Institute | Anaheim | California | 92801 | United States | ||
| Sc Clinical Research, Inc. |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28611778 | Derived | Phillips S, Mistry S, Riva A, Cooksley H, Hadzhiolova-Lebeau T, Plavova S, Katzarov K, Simonova M, Zeuzem S, Woffendin C, Chen PJ, Peng CY, Chang TT, Lueth S, De Knegt R, Choi MS, Wedemeyer H, Dao M, Kim CW, Chu HC, Wind-Rotolo M, Williams R, Cooney E, Chokshi S. Peg-Interferon Lambda Treatment Induces Robust Innate and Adaptive Immunity in Chronic Hepatitis B Patients. Front Immunol. 2017 May 29;8:621. doi: 10.3389/fimmu.2017.00621. eCollection 2017. | |
| 26739688 |
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| pegIFNα-2a |
| Drug |
Syringe, Subcutaneous 180 μg, Once Weekly, 48 Weeks |
|
|
| PegIFN lambda | Drug | Syringe, Subcutaneous, 180 µg, Once weekly, 48 weeks |
|
|
| Entecavir | Drug | Tablet, Oral, 0.5 mg, Once daily, 12 weeks initial monotherapy followed by 48 weeks of combination therapy with PegIFN lambda |
|
|
| 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: 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: 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 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 |
| Garden Grove |
| California |
| 92844 |
| United States |
| University Of California, Davis Medical Center | Sacramento | California | 95817 | United States |
| Research And Education, Inc. | San Diego | California | 92105 | United States |
| Yale New Haven Hospital | New Haven | Connecticut | 06520 | United States |
| Atlanta Gastroenterology Associates, Llc | Atlanta | Georgia | 30308 | United States |
| Mercy Medical Center | Baltimore | Maryland | 21202 | United States |
| Gastro Center Of Maryland | Colombia | Maryland | 21045 | United States |
| Medical Procare, Pllc | Flushing | New York | 11355 | United States |
| Office Of Sing Chan Md | Flushing | New York | 11355 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Oregon Health & Science University | Portland | Oregon | 97239 | United States |
| University Of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | 15213 | United States |
| Local Institution | Camperdown | New South Wales | 2050 | Australia |
| Local Institution | Liverpool | New South Wales | 2170 | Australia |
| Local Institution | Westmead Nsw | New South Wales | 2145 | Australia |
| Local Institution | Clayton Vic | Victoria | 3168 | Australia |
| Local Institution | Heidelberg Vic | Victoria | 3084 | Australia |
| Local Institution | Melbourne | Victoria | 3004 | Australia |
| Local Institution | Fremantle | Western Australia | 6160 | Australia |
| Heritage Medical Research Clinic, University Of Calgary | Calgary | Alberta | T2N 4Z6 | Canada |
| Local Institution | Winnipeg | Manitoba | R3E 3P4 | Canada |
| Toronto General Hospital | Toronto | Ontario | M5G 2C4 | Canada |
| Toronto Western Hospital University Health Network | Toronto | Ontario | M5T 2S8 | Canada |
| Local Institution | Clichy | 92118 | France |
| Local Institution | Nice | 06202 | France |
| Local Institution | Paris | 75571 | France |
| Local Institution | Rennes | 35033 | France |
| Local Institution | Frankfurt | 60590 | Germany |
| Local Institution | Freiburg im Breisgau | 79106 | Germany |
| Local Institution | Hamburg | 20246 | Germany |
| Local Institution | Hanover | 30625 | Germany |
| Local Institution | Tübingen | 72076 | Germany |
| Local Institution | Hong Kong | 852 | Hong Kong |
| Local Institution | Shatin | 30-32 | Hong Kong |
| Local Institution | Tai Po | 852 | Hong Kong |
| Local Institution | Florence | 50012 | Italy |
| Local Institution | Roma | 00161 | Italy |
| Local Institution | Rotterdam | 3015 CE | Netherlands |
| Local Institution | Singapore | 119228 | Singapore |
| Local Institution | Singapore | 169608 | Singapore |
| Local Institution | Chuncheon | 200-704 | South Korea |
| Local Institution | Gyeonggi-do | 480-717 | South Korea |
| Local Institution | Seoul | 120-752 | South Korea |
| Local Institution | Seoul | 135-710 | South Korea |
| Local Institution | Seoul | 135-720 | South Korea |
| Local Institution | Seoul | 138-736 | South Korea |
| Local Institution | Kaohsiung City | 807 | Taiwan |
| Local Institution | Taichung | 404 | Taiwan |
| Local Institution | Tainan | 704 | Taiwan |
| Local Institution | Taipei | 100 | Taiwan |
| Local Institution | Taipei | 114 | Taiwan |
| Local Institution | Taoyuan | 333 | Taiwan |
| Derived |
| Chan HLY, Ahn SH, Chang TT, Peng CY, Wong D, Coffin CS, Lim SG, Chen PJ, Janssen HLA, Marcellin P, Serfaty L, Zeuzem S, Cohen D, Critelli L, Xu D, Wind-Rotolo M, Cooney E; LIRA-B Study Team. Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B: A randomized phase 2b study (LIRA-B). J Hepatol. 2016 May;64(5):1011-1019. doi: 10.1016/j.jhep.2015.12.018. Epub 2015 Dec 29. |
| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D018347 | Hepadnaviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C100416 | peginterferon alfa-2a |
| C000600496 | peginterferon lambda-1a |
| C413685 | entecavir |
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