Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01204762
First received: September 16, 2010
Last updated: July 23, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Hepatitis B Virus
Drug: pegIFN
Drug: pegIFNα-2a
Drug: PegIFN lambda
Drug: Entecavir
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Dose-Ranging Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Pegylated Interferon Lambda (BMS-914143) Monotherapy in Interferon-Naive Patients With Chronic Hepatitis B Virus Infection Who Are HBeAg-positive

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Part A: Proportion of subjects who achieve Hepatitis B e antigen (HBeAg) seroconversion [ Time Frame: 24 weeks post-dosing (Week 72) ] [ Designated as safety issue: No ]
  • Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Part A: Proportion of subjects with ALT normalization (≤ 1 x ULN) [ Time Frame: Weeks 24, 48, 72, 96, 120, 144, 168 and 192 ] [ Designated as safety issue: No ]
  • Part A: Hepatitis E antigen (HBeAg) loss [ Time Frame: Weeks 24, 48, 72, 96, 120, 144, 168 and 192 ] [ Designated as safety issue: No ]
  • Part A: HBeAg seroconversion [ Time Frame: Weeks 24, 48, 96, 120, 144, 168 and 192 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities [ Time Frame: Up to Week 24 ] [ Designated as safety issue: Yes ]
  • Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities [ Time Frame: Up to Week 72 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Part B: HBeAg seroconversion rate at 24 weeks off treatment [ Time Frame: Week 84 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Part B: HBeAg loss and seroconversion in subjects treated with Lambda/ETV regimen [ Time Frame: Weeks 12, 24, 36, 60 and 84 ] [ Designated as safety issue: No ]
  • Part B: HBeAg levels over time in subjects treated with Lambda/ETV regimen [ Time Frame: Weeks 4, 8, 12, 24, 36, 60, and 84 ] [ Designated as safety issue: No ]
  • Part B: biochemical response rates in subjects treated with Lambda/ETV regimen [ Time Frame: Weeks 4, 8, 12, 24, 36, 60, and 84 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Part B: Rate of resistance to ETV during treatment with the Lambda/ETV regimen [ Time Frame: Up to Week 84 ] [ Designated as safety issue: No ]

Enrollment: 197
Study Start Date: November 2010
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A Arm 1: pegIFN (180 μg) Drug: pegIFN
Syringe, Subcutaneous, 180 μg, Once Weekly, 48 weeks
Active Comparator: Part A Arm 2: pegIFNα-2a Drug: pegIFNα-2a
Syringe, Subcutaneous 180 μg, Once Weekly, 48 Weeks
Other Name: Pegasys
Experimental: Part B: pegIFN lambda + Entecavir Drug: PegIFN lambda
Syringe, Subcutaneous, 180 µg, Once weekly, 48 weeks
Other Name: BMS-914143
Drug: Entecavir
Tablet, Oral, 0.5 mg, Once daily, 12 weeks initial monotherapy followed by 48 weeks of combination therapy with PegIFN lambda
Other Name: Baraclude

Detailed Description:

Part B sub study is Open Label

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01204762

  Show 53 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01204762     History of Changes
Other Study ID Numbers: AI452-005, 2010-020387-38
Study First Received: September 16, 2010
Last Updated: July 23, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: National Health and Medical Research Council
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Institute of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency
United States: Food and Drug Administration
United States: Institutional Review Board
Hong Kong: Department of Health
Singapore: Clinical Trials & Epidemiology Research Unit (CTERU)
Singapore: Domain Specific Review Boards
Singapore: Health Sciences Authority
Korea: Food and Drug Administration
Taiwan: Department of Health
Taiwan: National Bureau of Controlled Drugs

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
DNA Virus Infections
Digestive System Diseases
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Entecavir
Interferons
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014