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

Hepatitis B Virus Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01204762
• Other study ID #: AI452-005
• Secondary ID: 2010-020387-38
• Status: Completed
• Phase: Phase 2
• First received: September 16, 2010
• Last updated: September 23, 2015
• Start date: November 2010
• Est. completion date: December 2013

Study information

• Verified date: September 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationAustralia: National Health and Medical Research CouncilCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Ministry of HealthGermany: Federal Institute for Drugs and Medical DevicesItaly: Ministry of HealthItaly: National Bioethics CommitteeItaly: National Institute of HealthItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthItaly: The Italian Medicines AgencyUnited States: Food and Drug AdministrationUnited States: Institutional Review BoardHong Kong: Department of HealthSingapore: Clinical Trials & Epidemiology Research Unit (CTERU)Singapore: Domain Specific Review BoardsSingapore: Health Sciences AuthorityKorea: Food and Drug AdministrationTaiwan: Department of HealthTaiwan: National Bureau of Controlled Drugs
• Study type: Interventional

Clinical Trial 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

Description:

Part B sub study is Open Label

Recruitment information / eligibility

• Status: Completed
• Enrollment: 197
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B Virus

Intervention

Drug:
• pegIFN
Syringe, Subcutaneous, 180 µg, Once Weekly, 48 weeks
• pegIFNa-2a
Syringe, Subcutaneous 180 µg, Once Weekly, 48 Weeks
• PegIFN lambda
Syringe, Subcutaneous, 180 µg, Once weekly, 48 weeks
• Entecavir
Tablet, Oral, 0.5 mg, Once daily, 12 weeks initial monotherapy followed by 48 weeks of combination therapy with PegIFN lambda

Locations

Country	Name	City	State
Australia	Local Institution	Camperdown	New South Wales
Australia	Local Institution	Clayton Vic	Victoria
Australia	Local Institution	Fremantle	Western Australia
Australia	Local Institution	Heidelberg Vic	Victoria
Australia	Local Institution	Liverpool	New South Wales
Australia	Local Institution	Melbourne	Victoria
Australia	Local Institution	Westmead Nsw	New South Wales
Canada	Heritage Medical Research Clinic, University Of Calgary	Calgary	Alberta
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Toronto Western Hospital University Health Network	Toronto	Ontario
Canada	Local Institution	Winnipeg	Manitoba
France	Local Institution	Clichy Cedex
France	Local Institution	Nice Cedex 03
France	Local Institution	Paris Cedex 12
France	Local Institution	Rennes Cedex 9
Germany	Local Institution	Frankfurt
Germany	Local Institution	Freiburg
Germany	Local Institution	Hamburg
Germany	Local Institution	Hannover
Germany	Local Institution	Tuebingen
Hong Kong	Local Institution	Hong Kong
Hong Kong	Local Institution	Shatin
Hong Kong	Local Institution	Tai Po
Italy	Local Institution	Firenze
Italy	Local Institution	Roma
Korea, Republic of	Local Institution	Chuncheon
Korea, Republic of	Local Institution	Gyeonggi-Do
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Netherlands	Local Institution	Rotterdam
Singapore	Local Institution	Singapore
Singapore	Local Institution	Singapore
Taiwan	Local Institution	Kaohsiung
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Tainan
Taiwan	Local Institution	Taipei
Taiwan	Local Institution	Taipei
Taiwan	Local Institution	Taoyuan
United States	Advanced Clinical Research Institute	Anaheim	California
United States	Atlanta Gastroenterology Associates, Llc	Atlanta	Georgia
United States	Mercy Medical Center	Baltimore	Maryland
United States	Gastro Center Of Maryland	Colombia	Maryland
United States	Duke University Medical Center	Durham	North Carolina
United States	Medical Procare, Pllc	Flushing	New York
United States	Office Of Sing Chan Md	Flushing	New York
United States	Sc Clinical Research, Inc.	Garden Grove	California
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	University Of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	University Of California, Davis Medical Center	Sacramento	California
United States	Research And Education, Inc.	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Hong Kong,  Italy,  Korea, Republic of,  Netherlands,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Proportion of subjects who achieve Hepatitis B e antigen (HBeAg) seroconversion		24 weeks post-dosing (Week 72)	No
Primary	Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events		Week 24	Yes
Primary	Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events		24 weeks post-dosing (Week 72)	Yes
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	Part A: Proportion of subjects with ALT normalization (= 1 x ULN)		Weeks 24, 48, 72, 96, 120, 144, 168 and 192	No
Secondary	Part A: Hepatitis E antigen (HBeAg) loss		Weeks 24, 48, 72, 96, 120, 144, 168 and 192	No
Secondary	Part A: HBeAg seroconversion		Weeks 24, 48, 96, 120, 144, 168 and 192	No
Secondary	Part A: Mean change from baseline in log10 quantitative HBeAg levels over time		Baseline (Day 1), Weeks 24, 48, 96, 120, 144, 168 and 192	No
Secondary	Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities		Up to Week 24	Yes
Secondary	Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities		Up to Week 72	Yes
Secondary	Part A: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Pegylated interferon lambda (pegIFN?) will be derived from serum concentration versus time data		Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48	No
Secondary	Part A: Pharmacokinetic (PK) parameter Time of maximum observed concentration (Tmax) of Pegylated interferon lambda (pegIFN?) will be derived from serum concentration versus time data		Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48	No
Secondary	Part A: Pharmacokinetic (PK) parameter Trough serum concentration pre-dose (C0) of Pegylated interferon lambda (pegIFN?) will be derived from serum concentration versus time data		Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48	No
Secondary	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 pegIFN? will be derived from serum concentration versus time data		Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48	No
Secondary	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 pegIFN? will be derived from serum concentration versus time data		Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48	No
Secondary	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 pegIFN? will be derived from serum concentration versus time data		Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48	No
Secondary	Part B: HBeAg seroconversion rate at 24 weeks off treatment		Week 84	No
Secondary	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		Weeks 4, 8, 12, 24, 36, 60, and 84	No
Secondary	Part B: Mean change from baseline in HBV DNA over time in subjects treated with Lambda/ETV		Weeks 4, 8, 12, 24, 36, 60, and 84	No
Secondary	Part B: HBeAg loss and seroconversion in subjects treated with Lambda/ETV regimen		Weeks 12, 24, 36, 60 and 84	No
Secondary	Part B: HBeAg levels over time in subjects treated with Lambda/ETV regimen		Weeks 4, 8, 12, 24, 36, 60, and 84	No
Secondary	Part B: biochemical response rates in subjects treated with Lambda/ETV regimen		Weeks 4, 8, 12, 24, 36, 60, and 84	No
Secondary	Part B: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Lambda/ETV regimen will be derived from serum concentration versus time data		Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60	No
Secondary	Part B: Pharmacokinetic (PK) parameter Time of maximum observed concentration (Tmax) of Lambda/ETV regimen will be derived from serum concentration versus time data		Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60	No
Secondary	Part B: Pharmacokinetic (PK) parameter Trough serum concentration pre-dose (C0) of Lambda/ETV regimen will be derived from serum concentration versus time data		Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60	No
Secondary	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		Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60	No
Secondary	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		Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60	No
Secondary	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		Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60	No
Secondary	Part B: Rate of resistance to ETV during treatment with the Lambda/ETV regimen		Up to Week 84	No

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