Clinical trial NCT01204762: Dose Ranging Study of Pegylated Interferon Lambda in Patients With Hepatitis B and Positive for the Hepatitis B e Antigen
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis B Virus
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2010-09-17
Enrollment: 197
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: Part A: Proportion of subjects who achieve Hepatitis B e antigen (HBeAg) seroconversion
timeFrame: 24 weeks post-dosing (Week 72)
measure: Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events
timeFrame: Week 24
measure: Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events
timeFrame: 24 weeks post-dosing (Week 72)
measure: Part B: Safety and tolerability of Lambda/ETV regimen as measured by the frequency of SAEs and discontinuations due to AEs
timeFrame: Up to 84 Weeks
Secondary outcomes:
measure: 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
timeFrame: Weeks 24, 48, 72, 96, 120, 144, 168 and 192
measure: 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))
timeFrame: Baseline (Day 1), Weeks 24, 48, 72, 96, 120, 144, 168 and 192
measure: Part A: Proportion of subjects with ALT normalization (≤ 1 x ULN)
timeFrame: Weeks 24, 48, 72, 96, 120, 144, 168 and 192
measure: Part A: Hepatitis E antigen (HBeAg) loss
timeFrame: Weeks 24, 48, 72, 96, 120, 144, 168 and 192
measure: Part A: HBeAg seroconversion
timeFrame: Weeks 24, 48, 96, 120, 144, 168 and 192
measure: Part A: Mean change from baseline in log10 quantitative HBeAg levels over time
timeFrame: Baseline (Day 1), Weeks 24, 48, 96, 120, 144, 168 and 192
measure: Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities
timeFrame: Up to Week 24
measure: Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities
timeFrame: Up to Week 72
measure: Part A: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Pegylated interferon lambda (pegIFNλ) will be derived from serum concentration versus time data
timeFrame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48
measure: 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
timeFrame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48
measure: 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
timeFrame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48
measure: 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
timeFrame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48
measure: 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
timeFrame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48
measure: 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
timeFrame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48
measure: Part B: HBeAg seroconversion rate at 24 weeks off treatment
timeFrame: Week 84
measure: 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
timeFrame: Weeks 4, 8, 12, 24, 36, 60, and 84
measure: Part B: Mean change from baseline in HBV DNA over time in subjects treated with Lambda/ETV
timeFrame: Weeks 4, 8, 12, 24, 36, 60, and 84
measure: Part B: HBeAg loss and seroconversion in subjects treated with Lambda/ETV regimen
timeFrame: Weeks 12, 24, 36, 60 and 84
measure: Part B: HBeAg levels over time in subjects treated with Lambda/ETV regimen
timeFrame: Weeks 4, 8, 12, 24, 36, 60, and 84
measure: Part B: biochemical response rates in subjects treated with Lambda/ETV regimen
timeFrame: Weeks 4, 8, 12, 24, 36, 60, and 84
measure: Part B: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Lambda/ETV regimen will be derived from serum concentration versus time data
timeFrame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60
measure: Part B: Pharmacokinetic (PK) parameter Time of maximum observed concentration (Tmax) of Lambda/ETV regimen will be derived from serum concentration versus time data
timeFrame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60
measure: Part B: Pharmacokinetic (PK) parameter Trough serum concentration pre-dose (C0) of Lambda/ETV regimen will be derived from serum concentration versus time data
timeFrame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60
measure: 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
timeFrame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60
measure: 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
timeFrame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60
measure: 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
timeFrame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60
measure: Part B: Rate of resistance to ETV during treatment with the Lambda/ETV regimen
timeFrame: Up to Week 84
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Advanced Clinical Research Institute
state: California
city: Garden Grove
country: United States
facility: Sc Clinical Research, Inc.
state: California
city: Sacramento
country: United States
facility: University Of California, Davis Medical Center
state: California
city: San Diego
country: United States
facility: Research And Education, Inc.
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates, Llc
state: Georgia
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Colombia
country: United States
facility: Gastro Center Of Maryland
state: Maryland
city: Flushing
country: United States
facility: Medical Procare, Pllc
state: New York
city: Flushing
country: United States
facility: Office Of Sing Chan Md
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Pittsburgh
country: United States
facility: University Of Pittsburgh Medical Center
state: Pennsylvania
city: Camperdown
country: Australia
facility: Local Institution
state: New South Wales
city: Liverpool
country: Australia
facility: Local Institution
state: New South Wales
city: Westmead Nsw
country: Australia
facility: Local Institution
state: New South Wales
city: Clayton Vic
country: Australia
facility: Local Institution
state: Victoria
city: Heidelberg Vic
country: Australia
facility: Local Institution
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution
state: Victoria
city: Fremantle
country: Australia
facility: Local Institution
state: Western Australia
city: Calgary
country: Canada
facility: Heritage Medical Research Clinic, University Of Calgary
state: Alberta
city: Winnipeg
country: Canada
facility: Local Institution
state: Manitoba
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital University Health Network
state: Ontario
city: Clichy Cedex
country: France
facility: Local Institution
city: Nice Cedex 03
country: France
facility: Local Institution
city: Paris Cedex 12
country: France
facility: Local Institution
city: Rennes Cedex 9
country: France
facility: Local Institution
city: Frankfurt
country: Germany
facility: Local Institution
city: Freiburg
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Hannover
country: Germany
facility: Local Institution
city: Tuebingen
country: Germany
facility: Local Institution
city: Hong Kong
country: Hong Kong
facility: Local Institution
city: Shatin
country: Hong Kong
facility: Local Institution
city: Tai Po
country: Hong Kong
facility: Local Institution
city: Firenze
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Chuncheon
country: Korea, Republic of
facility: Local Institution
city: Gyeonggi-Do
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Rotterdam
country: Netherlands
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution
city: Kaohsiung
country: Taiwan
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Tainan
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taoyuan
country: Taiwan
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.