Dose Ranging Study of Pegylated Interferon Lambda in Patients With Hepatitis B and Positive for the Hepatitis B e Antigen

NCT01204762 | Completed Phase 2

• 2 other identifiers: AI452-0052010-020387-38
• Study Type: interventional
• Target: 197
• Locations: 11 countries
• Sites: 53

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

Conditions

Hepatitis B Virus

Outcome Measures

Primary Outcomes (4)

• 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

Secondary Outcomes (27)

• 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 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

Study Arms (3)

Part A Arm 1: pegIFN (180 μg)

EXPERIMENTAL

Drug: pegIFN

Part A Arm 2: pegIFNα-2a

ACTIVE COMPARATOR

Drug: pegIFNα-2a

Part B: pegIFN lambda + Entecavir

EXPERIMENTAL

Drug: PegIFN lambda; Drug: Entecavir

Interventions

pegIFN DRUG

Syringe, Subcutaneous, 180 μg, Once Weekly, 48 weeks

Part A Arm 1: pegIFN (180 μg)

pegIFNα-2a DRUG

Syringe, Subcutaneous 180 μg, Once Weekly, 48 Weeks

Also known as: Pegasys

Part A Arm 2: pegIFNα-2a

PegIFN lambda DRUG

Syringe, Subcutaneous, 180 µg, Once weekly, 48 weeks

Also known as: BMS-914143

Part B: pegIFN lambda + Entecavir

Entecavir DRUG

Tablet, Oral, 0.5 mg, Once daily, 12 weeks initial monotherapy followed by 48 weeks of combination therapy with PegIFN lambda

Also known as: Baraclude

Part B: pegIFN lambda + Entecavir

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (53)

Advanced Clinical Research Institute

Anaheim, California, 92801, United States

Location

Sc Clinical Research, Inc.

Garden Grove, California, 92844, United States

Location

University Of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

Research And Education, Inc.

San Diego, California, 92105, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

Atlanta Gastroenterology Associates, Llc

Atlanta, Georgia, 30308, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Gastro Center Of Maryland

Colombia, Maryland, 21045, United States

Location

Medical Procare, Pllc

Flushing, New York, 11355, United States

Location

Office Of Sing Chan Md

Flushing, New York, 11355, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University Of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Local Institution

Camperdown, New South Wales, 2050, Australia

Location

Local Institution

Liverpool, New South Wales, 2170, Australia

Location

Local Institution

Westmead Nsw, New South Wales, 2145, Australia

Location

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Clayton Vic, Victoria, 3168, Australia

Location

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Heidelberg Vic, Victoria, 3084, Australia

Location

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Melbourne, Victoria, 3004, Australia

Location

Local Institution

Fremantle, Western Australia, 6160, Australia

Location

Heritage Medical Research Clinic, University Of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

Local Institution

Winnipeg, Manitoba, R3E 3P4, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Toronto Western Hospital University Health Network

Toronto, Ontario, M5T 2S8, Canada

Location

Local Institution

Clichy, 92118, France

Location

Local Institution

Nice, 06202, France

Location

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Paris, 75571, France

Location

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Rennes, 35033, France

Location

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Frankfurt, 60590, Germany

Location

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Freiburg im Breisgau, 79106, Germany

Location

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Hamburg, 20246, Germany

Location

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Hanover, 30625, Germany

Location

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Tübingen, 72076, Germany

Location

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Hong Kong, 852, Hong Kong

Location

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Shatin, 30-32, Hong Kong

Location

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Tai Po, 852, Hong Kong

Location

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Florence, 50012, Italy

Location

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Roma, 00161, Italy

Location

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Rotterdam, 3015 CE, Netherlands

Location

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Singapore, 119228, Singapore

Location

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Singapore, 169608, Singapore

Location

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Chuncheon, 200-704, South Korea

Location

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Gyeonggi-do, 480-717, South Korea

Location

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Seoul, 120-752, South Korea

Location

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Seoul, 135-710, South Korea

Location

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Seoul, 135-720, South Korea

Location

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Seoul, 138-736, South Korea

Location

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Kaohsiung City, 807, Taiwan

Location

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Taichung, 404, Taiwan

Location

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Tainan, 704, Taiwan

Location

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Taipei, 100, Taiwan

Location

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Taipei, 114, Taiwan

Location

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Taoyuan District, 333, Taiwan

Location

Related Publications (2)

• 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.

  PMID: 28611778 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.

  PMID: 26739688 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Hepatitis B

Interventions

peginterferon alfa-2a; peginterferon lambda-1a; entecavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2010
• First Posted: September 17, 2010
• Study Start: November 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: October 9, 2015

Record last verified: 2015-09

Locations

KR (6); IT (2); TW (6); HK (3); AU (7); DE (5); US (13); NL (1); SG (2); CA (4); FR (4)