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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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/ct2/show/NCT01204762
Trial related presentations / publications
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/ct2/show/NCT01204762