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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01204762




Registration number
NCT01204762
Ethics application status
Date submitted
16/09/2010
Date registered
17/09/2010
Date last updated
9/10/2015

Titles & IDs
Public title
Dose Ranging Study of Pegylated Interferon Lambda in Patients With Hepatitis B and Positive for the Hepatitis B e Antigen
Scientific 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
Secondary ID [1] 0 0
2010-020387-38
Secondary ID [2] 0 0
AI452-005
Universal Trial Number (UTN)
Trial acronym
LIRA-B
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B Virus 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - pegIFN
Treatment: Drugs - pegIFNa-2a
Treatment: Drugs - PegIFN lambda
Treatment: Drugs - Entecavir

Experimental: Part A Arm 1: pegIFN (180 µg) -

Active comparator: Part A Arm 2: pegIFNa-2a -

Experimental: Part B: pegIFN lambda + Entecavir -


Treatment: Drugs: pegIFN
Syringe, Subcutaneous, 180 µg, Once Weekly, 48 weeks

Treatment: Drugs: pegIFNa-2a
Syringe, Subcutaneous 180 µg, Once Weekly, 48 Weeks

Treatment: Drugs: PegIFN lambda
Syringe, Subcutaneous, 180 µg, Once weekly, 48 weeks

Treatment: Drugs: Entecavir
Tablet, Oral, 0.5 mg, Once daily, 12 weeks initial monotherapy followed by 48 weeks of combination therapy with PegIFN lambda
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A: Proportion of subjects who achieve Hepatitis B e antigen (HBeAg) seroconversion
Timepoint [1] 0 0
24 weeks post-dosing (Week 72)
Primary outcome [2] 0 0
Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events
Timepoint [2] 0 0
Week 24
Primary outcome [3] 0 0
Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events
Timepoint [3] 0 0
24 weeks post-dosing (Week 72)
Primary outcome [4] 0 0
Part B: Safety and tolerability of Lambda/ETV regimen as measured by the frequency of SAEs and discontinuations due to AEs
Timepoint [4] 0 0
Up to 84 Weeks
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Weeks 24, 48, 72, 96, 120, 144, 168 and 192
Secondary outcome [2] 0 0
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))
Timepoint [2] 0 0
Baseline (Day 1), Weeks 24, 48, 72, 96, 120, 144, 168 and 192
Secondary outcome [3] 0 0
Part A: Proportion of subjects with ALT normalization (= 1 x ULN)
Timepoint [3] 0 0
Weeks 24, 48, 72, 96, 120, 144, 168 and 192
Secondary outcome [4] 0 0
Part A: Hepatitis E antigen (HBeAg) loss
Timepoint [4] 0 0
Weeks 24, 48, 72, 96, 120, 144, 168 and 192
Secondary outcome [5] 0 0
Part A: HBeAg seroconversion
Timepoint [5] 0 0
Weeks 24, 48, 96, 120, 144, 168 and 192
Secondary outcome [6] 0 0
Part A: Mean change from baseline in log10 quantitative HBeAg levels over time
Timepoint [6] 0 0
Baseline (Day 1), Weeks 24, 48, 96, 120, 144, 168 and 192
Secondary outcome [7] 0 0
Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities
Timepoint [7] 0 0
Up to Week 24
Secondary outcome [8] 0 0
Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities
Timepoint [8] 0 0
Up to Week 72
Secondary outcome [9] 0 0
Part A: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Pegylated interferon lambda (pegIFN?) will be derived from serum concentration versus time data
Timepoint [9] 0 0
Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48
Secondary outcome [11] 0 0
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
Timepoint [11] 0 0
Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48
Secondary outcome [13] 0 0
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
Timepoint [13] 0 0
Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48
Secondary outcome [14] 0 0
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
Timepoint [14] 0 0
Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48
Secondary outcome [15] 0 0
Part B: HBeAg seroconversion rate at 24 weeks off treatment
Timepoint [15] 0 0
Week 84
Secondary outcome [16] 0 0
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
Timepoint [16] 0 0
Weeks 4, 8, 12, 24, 36, 60, and 84
Secondary outcome [17] 0 0
Part B: Mean change from baseline in HBV DNA over time in subjects treated with Lambda/ETV
Timepoint [17] 0 0
Weeks 4, 8, 12, 24, 36, 60, and 84
Secondary outcome [18] 0 0
Part B: HBeAg loss and seroconversion in subjects treated with Lambda/ETV regimen
Timepoint [18] 0 0
Weeks 12, 24, 36, 60 and 84
Secondary outcome [19] 0 0
Part B: HBeAg levels over time in subjects treated with Lambda/ETV regimen
Timepoint [19] 0 0
Weeks 4, 8, 12, 24, 36, 60, and 84
Secondary outcome [20] 0 0
Part B: biochemical response rates in subjects treated with Lambda/ETV regimen
Timepoint [20] 0 0
Weeks 4, 8, 12, 24, 36, 60, and 84
Secondary outcome [21] 0 0
Part B: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Lambda/ETV regimen will be derived from serum concentration versus time data
Timepoint [21] 0 0
Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60
Secondary outcome [22] 0 0
Part B: Pharmacokinetic (PK) parameter Time of maximum observed concentration (Tmax) of Lambda/ETV regimen will be derived from serum concentration versus time data
Timepoint [22] 0 0
Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60
Secondary outcome [23] 0 0
Part B: Pharmacokinetic (PK) parameter Trough serum concentration pre-dose (C0) of Lambda/ETV regimen will be derived from serum concentration versus time data
Timepoint [23] 0 0
Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60
Secondary outcome [24] 0 0
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
Timepoint [24] 0 0
Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60
Secondary outcome [25] 0 0
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
Timepoint [25] 0 0
Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60
Secondary outcome [26] 0 0
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
Timepoint [26] 0 0
Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60
Secondary outcome [27] 0 0
Part B: Rate of resistance to ETV during treatment with the Lambda/ETV regimen
Timepoint [27] 0 0
Up to Week 84

Eligibility
Key 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
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2013
Sample size
Target
Accrual to date
Final
197
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Local Institution - Camperdown
Recruitment hospital [2] 0 0
Local Institution - Liverpool
Recruitment hospital [3] 0 0
Local Institution - Westmead Nsw
Recruitment hospital [4] 0 0
Local Institution - Clayton Vic
Recruitment hospital [5] 0 0
Local Institution - Heidelberg Vic
Recruitment hospital [6] 0 0
Local Institution - Melbourne
Recruitment hospital [7] 0 0
Local Institution - Fremantle
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
2145 - Westmead Nsw
Recruitment postcode(s) [4] 0 0
3168 - Clayton Vic
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg Vic
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment postcode(s) [7] 0 0
6160 - Fremantle
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
Canada
State/province [9] 0 0
Alberta
Country [10] 0 0
Canada
State/province [10] 0 0
Manitoba
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
France
State/province [12] 0 0
Clichy Cedex
Country [13] 0 0
France
State/province [13] 0 0
Nice Cedex 03
Country [14] 0 0
France
State/province [14] 0 0
Paris Cedex 12
Country [15] 0 0
France
State/province [15] 0 0
Rennes Cedex 9
Country [16] 0 0
Germany
State/province [16] 0 0
Frankfurt
Country [17] 0 0
Germany
State/province [17] 0 0
Freiburg
Country [18] 0 0
Germany
State/province [18] 0 0
Hamburg
Country [19] 0 0
Germany
State/province [19] 0 0
Hannover
Country [20] 0 0
Germany
State/province [20] 0 0
Tuebingen
Country [21] 0 0
Hong Kong
State/province [21] 0 0
Hong Kong
Country [22] 0 0
Hong Kong
State/province [22] 0 0
Shatin
Country [23] 0 0
Hong Kong
State/province [23] 0 0
Tai Po
Country [24] 0 0
Italy
State/province [24] 0 0
Firenze
Country [25] 0 0
Italy
State/province [25] 0 0
Roma
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Chuncheon
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Gyeonggi-Do
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Seoul
Country [29] 0 0
Netherlands
State/province [29] 0 0
Rotterdam
Country [30] 0 0
Singapore
State/province [30] 0 0
Singapore
Country [31] 0 0
Taiwan
State/province [31] 0 0
Kaohsiung
Country [32] 0 0
Taiwan
State/province [32] 0 0
Taichung
Country [33] 0 0
Taiwan
State/province [33] 0 0
Tainan
Country [34] 0 0
Taiwan
State/province [34] 0 0
Taipei
Country [35] 0 0
Taiwan
State/province [35] 0 0
Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
At least 1 dose of pegIFN? 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
Trial website
https://clinicaltrials.gov/study/NCT01204762
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01204762