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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

September 16, 2010
July 23, 2014
November 2010
December 2013   (final data collection date for primary outcome measure)
  • 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 ]
  • Proportion of subjects who achieve HBeAg seroconversion [ Time Frame: 24 weeks post-dosing (Week 72) ] [ Designated as safety issue: No ]
  • 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 ]
  • 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 ]
Complete list of historical versions of study NCT01204762 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Proportion of subjects who achieve an HBV DNA < 50 IU/mL (approximately 300 copies/mL) using the Roche COBAS® TaqMan - HPS assay [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Proportion of subjects who achieve an HBV DNA < 50 IU/mL (approximately 300 copies/mL) using the Roche COBAS® TaqMan - HPS assay [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Proportion of subjects who achieve an HBV DNA < 50 IU/mL (approximately 300 copies/mL) using the Roche COBAS® TaqMan - HPS assay [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  • Proportion of subjects who achieve an HBV DNA < 50 IU/mL (approximately 300 copies/mL) at Weeks 48 using the Roche COBAS® TaqMan - HPS assay [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Mean change from baseline in log10 HBV DNA levels over time (Proportion of subjects with ALT normalization (≤ 1 x ULN) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Mean change from baseline in log10 HBV DNA levels over time (Proportion of subjects with ALT normalization (≤ 1 x ULN) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Mean change from baseline in log10 HBV DNA levels over time (Proportion of subjects with ALT normalization (≤ 1 x ULN) [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  • HBeAg loss [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • HBeAg loss [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • HBeAg loss [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  • HBeAg seroconversion [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • HBeAg seroconversion [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Mean change from baseline in log10 quantitative HBeAg levels [ Time Frame: Duration of trial (Week 24) ] [ Designated as safety issue: No ]
  • Mean change from baseline in log10 quantitative HBeAg levels [ Time Frame: Duration of trial (Week 72) ] [ Designated as safety issue: No ]
  • Number and percent of subjects with adverse events (AEs) or laboratory abnormalities [ Time Frame: Duration of trial (Week 24) ] [ Designated as safety issue: Yes ]
  • Number and percent of subjects with adverse events (AEs) or laboratory abnormalities [ Time Frame: Duration of trial (Week 72) and upon occurrence ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic parameters 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 ]
Not Provided
Not Provided
 
Dose Ranging Study of Pegylated Interferon Lambda in Patients With Hepatitis B and Positive for the Hepatitis B e Antigen
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

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

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hepatitis B Virus
  • Drug: pegIFN
    Syringe, Subcutaneous, 180 μg, Once Weekly, 48 weeks
  • Drug: pegIFNα-2a
    Syringe, Subcutaneous 180 μg, Once Weekly, 48 Weeks
    Other Name: Pegasys
  • 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
  • Experimental: Part A Arm 1: pegIFN (180 μg)
    Intervention: Drug: pegIFN
  • Active Comparator: Part A Arm 2: pegIFNα-2a
    Intervention: Drug: pegIFNα-2a
  • Experimental: Part B: pegIFN lambda + Entecavir
    Interventions:
    • Drug: PegIFN lambda
    • Drug: Entecavir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
197
December 2013
December 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   France,   Germany,   Hong Kong,   Italy,   Korea, Republic of,   Netherlands,   Singapore,   Taiwan
 
NCT01204762
AI452-005, 2010-020387-38
No
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP