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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)

Primary Purpose

Hepatitis B Virus

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

pegIFN

pegIFNα-2a

PegIFN lambda

Entecavir

About this trial

This is an interventional treatment trial for Hepatitis B Virus

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

Part A Arm 1: pegIFN (180 μg)

Part A Arm 2: pegIFNα-2a

Part B: pegIFN lambda + Entecavir

Arm Description

Outcomes

Primary Outcome Measures

Part A: Proportion of subjects who achieve Hepatitis B e antigen (HBeAg) seroconversion

Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events

Part B: Safety and tolerability of Lambda/ETV regimen as measured by the frequency of SAEs and discontinuations due to AEs

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

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))

Part A: Proportion of subjects with ALT normalization (≤ 1 x ULN)

Part A: Hepatitis E antigen (HBeAg) loss

Part A: HBeAg seroconversion

Part A: Mean change from baseline in log10 quantitative HBeAg levels over time

Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities

Part A: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Pegylated interferon lambda (pegIFNλ) will be derived from serum concentration versus time data

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

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

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

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

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

Part B: HBeAg seroconversion rate at 24 weeks off treatment

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

Part B: Mean change from baseline in HBV DNA over time in subjects treated with Lambda/ETV

Part B: HBeAg loss and seroconversion in subjects treated with Lambda/ETV regimen

Part B: HBeAg levels over time in subjects treated with Lambda/ETV regimen

Part B: biochemical response rates in subjects treated with Lambda/ETV regimen

Part B: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Lambda/ETV regimen will be derived from serum concentration versus time data

Part B: Pharmacokinetic (PK) parameter Time of maximum observed concentration (Tmax) of Lambda/ETV regimen will be derived from serum concentration versus time data

Part B: Pharmacokinetic (PK) parameter Trough serum concentration pre-dose (C0) of Lambda/ETV regimen will be derived from serum concentration versus time data

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

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

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

Part B: Rate of resistance to ETV during treatment with the Lambda/ETV regimen

Full Information

NCT ID

NCT01204762

First Posted

September 16, 2010

Last Updated

September 23, 2015

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT01204762

Brief Title

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

Acronym

LIRA-B

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2015

Overall Recruitment Status

Completed

Study Start Date

November 2010 (undefined)

Primary Completion Date

December 2013 (Actual)

Study Completion Date

December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis B Virus

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

197 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A Arm 1: pegIFN (180 μg)

Arm Type

Experimental

Arm Title

Part A Arm 2: pegIFNα-2a

Arm Type

Active Comparator

Arm Title

Part B: pegIFN lambda + Entecavir

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

pegIFN

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

pegIFNα-2a

Other Intervention Name(s)

Pegasys

Intervention Description

Syringe, Subcutaneous 180 μg, Once Weekly, 48 Weeks

Intervention Type

Drug

Intervention Name(s)

PegIFN lambda

Other Intervention Name(s)

BMS-914143

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Entecavir

Other Intervention Name(s)

Baraclude

Intervention Description

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

Primary Outcome Measure Information:

Title

Part A: Proportion of subjects who achieve Hepatitis B e antigen (HBeAg) seroconversion

Time Frame

24 weeks post-dosing (Week 72)

Title

Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events

Time Frame

Week 24

Title

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)

Title

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

Secondary Outcome Measure Information:

Title

Time Frame

Weeks 24, 48, 72, 96, 120, 144, 168 and 192

Title

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

Title

Part A: Proportion of subjects with ALT normalization (≤ 1 x ULN)

Time Frame

Weeks 24, 48, 72, 96, 120, 144, 168 and 192

Title

Part A: Hepatitis E antigen (HBeAg) loss

Time Frame

Weeks 24, 48, 72, 96, 120, 144, 168 and 192

Title

Part A: HBeAg seroconversion

Time Frame

Weeks 24, 48, 96, 120, 144, 168 and 192

Title

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

Title

Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities

Time Frame

Up to Week 24

Title

Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities

Time Frame

Up to Week 72

Title

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

Title

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

Title

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

Title

Time Frame

Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48

Title

Time Frame

Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48

Title

Time Frame

Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48

Title

Part B: HBeAg seroconversion rate at 24 weeks off treatment

Time Frame

Week 84

Title

Time Frame

Weeks 4, 8, 12, 24, 36, 60, and 84

Title

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

Title

Part B: HBeAg loss and seroconversion in subjects treated with Lambda/ETV regimen

Time Frame

Weeks 12, 24, 36, 60 and 84

Title

Part B: HBeAg levels over time in subjects treated with Lambda/ETV regimen

Time Frame

Weeks 4, 8, 12, 24, 36, 60, and 84

Title

Part B: biochemical response rates in subjects treated with Lambda/ETV regimen

Time Frame

Weeks 4, 8, 12, 24, 36, 60, and 84

Title

Part B: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Lambda/ETV regimen will be derived from serum concentration versus time data

Time Frame