Dose Ranging Study of Pegylated Interferon Lambda in Patients With Hepatitis B and Positive for the Hepatitis B e Antigen (LIRA-B)
This study is currently recruiting participants.
Verified June 2013 by Bristol-Myers Squibb
Sponsor:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01204762
First received: September 16, 2010
Last updated: June 17, 2013
Last verified: June 2013
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Purpose
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
| Condition | Intervention | Phase |
|---|---|---|
|
Hepatitis B Virus |
Drug: pegIFN Drug: pegIFNα-2a Drug: PegIFN lambda Drug: Entecavir |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Drug Information available for:
Interferon
Entecavir
Recombinant Hepatitis B vaccine
Hepatitis A Vaccines
U.S. FDA Resources
Further study details as provided by Bristol-Myers Squibb:
Primary Outcome Measures:
- Part A: Proportion of subjects who achieve Hepatitis B e antigen (HBeAg) seroconversion [ Time Frame: 24 weeks post-dosing (Week 72) ] [ Designated as safety issue: No ]
- Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events [ Time Frame: Week 24 ] [ Designated as safety issue: Yes ]
- 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) ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Weeks 24, 48, 72, 96, 120, 144, 168 and 192 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Part A: Proportion of subjects with ALT normalization (≤ 1 x ULN) [ Time Frame: Weeks 24, 48, 72, 96, 120, 144, 168 and 192 ] [ Designated as safety issue: No ]
- Part A: Hepatitis E antigen (HBeAg) loss [ Time Frame: Weeks 24, 48, 72, 96, 120, 144, 168 and 192 ] [ Designated as safety issue: No ]
- Part A: HBeAg seroconversion [ Time Frame: Weeks 24, 48, 96, 120, 144, 168 and 192 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities [ Time Frame: Up to Week 24 ] [ Designated as safety issue: Yes ]
- Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities [ Time Frame: Up to Week 72 ] [ Designated as safety issue: Yes ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 [ Time Frame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48 ] [ Designated as safety issue: No ]
- 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 [ Time Frame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48 ] [ Designated as safety issue: No ]
- 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 [ Time Frame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48 ] [ Designated as safety issue: No ]
- Part B: HBeAg seroconversion rate at 24 weeks off treatment [ Time Frame: Week 84 ] [ Designated as safety issue: No ]
- 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 [ Time Frame: Weeks 4, 8, 12, 24, 36, 60, and 84 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Part B: HBeAg loss and seroconversion in subjects treated with Lambda/ETV regimen [ Time Frame: Weeks 12, 24, 36, 60 and 84 ] [ Designated as safety issue: No ]
- Part B: HBeAg levels over time in subjects treated with Lambda/ETV regimen [ Time Frame: Weeks 4, 8, 12, 24, 36, 60, and 84 ] [ Designated as safety issue: No ]
- Part B: biochemical response rates in subjects treated with Lambda/ETV regimen [ Time Frame: Weeks 4, 8, 12, 24, 36, 60, and 84 ] [ Designated as safety issue: No ]
- Part B: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Lambda/ETV regimen will be derived from serum concentration versus time data [ Time Frame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60 ] [ Designated as safety issue: No ]
- Part B: Pharmacokinetic (PK) parameter Time of maximum observed concentration (Tmax) of Lambda/ETV regimen will be derived from serum concentration versus time data [ Time Frame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60 ] [ Designated as safety issue: No ]
- Part B: Pharmacokinetic (PK) parameter Trough serum concentration pre-dose (C0) of Lambda/ETV regimen will be derived from serum concentration versus time data [ Time Frame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60 ] [ Designated as safety issue: No ]
- 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 [ Time Frame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60 ] [ Designated as safety issue: No ]
- 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 [ Time Frame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60 ] [ Designated as safety issue: No ]
- 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 [ Time Frame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60 ] [ Designated as safety issue: No ]
- Part B: Rate of resistance to ETV during treatment with the Lambda/ETV regimen [ Time Frame: Up to Week 84 ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 170 |
| Study Start Date: | November 2010 |
| Estimated Study Completion Date: | July 2017 |
| Estimated Primary Completion Date: | May 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Part A Arm 1: pegIFN (180 μg) |
Drug: pegIFN
Syringe, Subcutaneous, 180 μg, Once Weekly, 48 weeks
|
| Active Comparator: Part A Arm 2: pegIFNα-2a |
Drug: pegIFNα-2a
Syringe, Subcutaneous 180 μg, Once Weekly, 48 Weeks
Other Name: Pegasys
|
| Experimental: Part B: pegIFN lambda + Entecavir |
Drug: PegIFN lambda
Syringe, Subcutaneous, 180 µg, Once weekly, 48 weeks
Other Name: BMS-914143
Drug: Entecavir
Tablet, Oral, 0.5 mg, Once daily, 12 weeks initial monotherapy followed by 48 weeks of combination therapy with PegIFN lambda
Other Name: Baraclude
|
Detailed Description:
Part B sub study is Open Label
Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01204762
Hide Study Locations
Contacts
| Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email: | Clinical.Trials@bms.com | |
| Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time. |
Hide Study LocationsLocations
| United States, California | |
| Advanced Clinical Research Institute | Completed |
| Anaheim, California, United States, 92801 | |
| Sc Clinical Research, Inc. | Recruiting |
| Garden Grove, California, United States, 92844 | |
| Contact: Michael Dao, Site 073 714-364-1472 | |
| University Of California Davis Medical Center | Recruiting |
| Sacramento, California, United States, 95817 | |
| Contact: Christopher Bowlus, Site 033 916-734-0500 | |
| Research And Education, Inc. | Completed |
| San Diego, California, United States, 92105 | |
| United States, Connecticut | |
| Yale University School Of Medicine | Recruiting |
| New Haven, Connecticut, United States, 06520 | |
| Contact: Joseph K Lim, Site 037 203-785-4796 | |
| United States, Georgia | |
| Atlanta Gastroenterology Associates | Recruiting |
| Atlanta, Georgia, United States, 30308 | |
| Contact: Norman Gitlin, Site 027 404-253-6882 | |
| United States, Maryland | |
| Mercy Medical Center | Recruiting |
| Baltimore, Maryland, United States, 21202 | |
| Contact: Paul Thuluvath, Site 063 410-332-9754 | |
| Gastro Center Of Maryland | Recruiting |
| Colombia, Maryland, United States, 21045 | |
| Contact: Rudra Rai, Site 077 410-290-6677 | |
| United States, New York | |
| Medical Procare, Pllc | Recruiting |
| Flushing, New York, United States, 11355 | |
| Contact: Calvin Q Pan, Site 012 718-888-7728 ext 101 | |
| Office Of Sing Chan Md | Recruiting |
| Flushing, New York, United States, 11355 | |
| Contact: Sing Chan, Site 016 516-238-6855 | |
| United States, North Carolina | |
| Duke University Medical Center | Completed |
| Durham, North Carolina, United States, 27710 | |
| United States, Oregon | |
| Oregon Health Science University | Recruiting |
| Portland, Oregon, United States, 97239 | |
| Contact: Atif Zaman, Site 024 503-494-6865 | |
| United States, Pennsylvania | |
| University Of Pittsburgh Medical Center | Completed |
| Pittsburgh, Pennsylvania, United States, 15213 | |
| Australia, New South Wales | |
| Local Institution | Active, not recruiting |
| Camperdown, New South Wales, Australia, 2050 | |
| Local Institution | Completed |
| Liverpool, New South Wales, Australia, 2170 | |
| Local Institution | Completed |
| Westmead Nsw, New South Wales, Australia, 2145 | |
| Australia, Victoria | |
| Local Institution | Active, not recruiting |
| Clayton Vic, Victoria, Australia, 3168 | |
| Local Institution | Completed |
| Heidelberg Vic, Victoria, Australia, 3084 | |
| Local Institution | Completed |
| Melbourne, Victoria, Australia, 3004 | |
| Australia, Western Australia | |
| Local Institution | Completed |
| Fremantle, Western Australia, Australia, 6160 | |
| Canada, Alberta | |
| Local Institution | Active, not recruiting |
| Calgary, Alberta, Canada, T2N 4N1 | |
| Canada, Manitoba | |
| Local Institution | Completed |
| Winnipeg, Manitoba, Canada, R3E 3P4 | |
| Canada, Ontario | |
| Local Institution | Active, not recruiting |
| Toronto, Ontario, Canada, M5T 2S8 | |
| Local Institution | Active, not recruiting |
| Toronto, Ontario, Canada, M5G 2C4 | |
| France | |
| Local Institution | Active, not recruiting |
| Clichy Cedex, France, 92118 | |
| Local Institution | Completed |
| Nice Cedex 03, France, 06202 | |
| Local Institution | Completed |
| Paris Cedex 12, France, 75571 | |
| Local Institution | Completed |
| Rennes Cedex 9, France, 35033 | |
| Germany | |
| Local Institution | Recruiting |
| Frankfurt, Germany, 60590 | |
| Contact: Site 020 | |
| Local Institution | Recruiting |
| Freiburg, Germany, 79110 | |
| Contact: Site 052 | |
| Local Institution | Recruiting |
| Hamburg, Germany, 20246 | |
| Contact: Site 062 | |
| Local Institution | Recruiting |
| Hannover, Germany, 30625 | |
| Contact: Site 072 | |
| Local Institution | Completed |
| Tuebingen, Germany, 72076 | |
| Hong Kong | |
| Local Institution | Completed |
| Hong Kong, Hong Kong, 852 | |
| Local Institution | Active, not recruiting |
| Shatin, Hong Kong, 30-32 | |
| Local Institution | Active, not recruiting |
| Tai Po, Hong Kong, 852 | |
| Italy | |
| Local Institution | Recruiting |
| Firenze, Italy, 50012 | |
| Contact: Site 060 | |
| Local Institution | Recruiting |
| Roma, Italy, 00161 | |
| Contact: Site 061 | |
| Korea, Republic of | |
| Local Institution | Recruiting |
| Uijeongbu, Gyeonggi-Do, Korea, Republic of, 480-717 | |
| Contact: Site 075 | |
| Local Institution | Completed |
| Chuncheon, Korea, Republic of, 200-704 | |
| Local Institution | Active, not recruiting |
| Seoul, Korea, Republic of, 135-720 | |
| Local Institution | Completed |
| Seoul, Korea, Republic of, 120-752 | |
| Local Institution | Recruiting |
| Seoul, Korea, Republic of, 135-710 | |
| Contact: Site 068 | |
| Local Institution | Completed |
| Seoul, Korea, Republic of, 138736 | |
| Netherlands | |
| Local Institution | Active, not recruiting |
| Rotterdam, Netherlands, 3015 CE | |
| Singapore | |
| Local Institution | Active, not recruiting |
| Singapore, Singapore, 169608 | |
| Local Institution | Completed |
| Singapore, Singapore, 119228 | |
| Taiwan | |
| Local Institution | Active, not recruiting |
| Kaohsiung, Taiwan, 807 | |
| Local Institution | Active, not recruiting |
| Taichung, Taiwan, 404 | |
| Local Institution | Active, not recruiting |
| Tainan R.O.C., Taiwan, 70428 | |
| Local Institution | Active, not recruiting |
| Taipei, Taiwan, 100 | |
| Local Institution | Recruiting |
| Taipei, Taiwan, 114 | |
| Contact: Site 078 | |
| Local Institution | Recruiting |
| Taoyuan, Taiwan, 333 | |
| Contact: Site 069 | |
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
More Information
Additional Information:
No publications provided
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT01204762 History of Changes |
| Other Study ID Numbers: | AI452-005, 2010-020387-38 |
| Study First Received: | September 16, 2010 |
| Last Updated: | June 17, 2013 |
| Health Authority: | Australia: Department of Health and Ageing Therapeutic Goods Administration Australia: National Health and Medical Research Council Canada: Health Canada France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Ministry of Health Germany: Federal Institute for Drugs and Medical Devices Italy: Ministry of Health Italy: National Bioethics Committee Italy: National Institute of Health Italy: National Monitoring Centre for Clinical Trials - Ministry of Health Italy: The Italian Medicines Agency United States: Food and Drug Administration United States: Institutional Review Board Hong Kong: Department of Health Singapore: Clinical Trials & Epidemiology Research Unit (CTERU) Singapore: Domain Specific Review Boards Singapore: Health Sciences Authority Korea: Food and Drug Administration Taiwan: Department of Health Taiwan: National Bureau of Controlled Drugs |
Additional relevant MeSH terms:
|
Hepatitis Hepatitis A Hepatitis B Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections |
Hepadnaviridae Infections DNA Virus Infections Interferons Entecavir Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Antiviral Agents Anti-Infective Agents |
ClinicalTrials.gov processed this record on June 17, 2013