Study to Determine the Safety and Effectiveness of Antiviral Combination Therapy to Treat Hepatitis C Virus (HCV) Infected Patients Who Have Previously Not Been Treated With Standard of Care
This study is ongoing, but not recruiting participants.
Sponsor:
Bristol-Myers Squibb
Collaborator:
Pharmasset
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01359644
First received: May 23, 2011
Last updated: July 11, 2012
Last verified: July 2012
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
The purpose of the study is to determine whether therapy with the combination of PSI-7977 and BMS-790052 with or without Ribavirin is effective in treating Hepatitis C infection when given for 12 or 24 weeks as measured by sustained virologic response (SVR) with undetectable HCV RNA 12 weeks post treatment
| Condition | Intervention | Phase |
|---|---|---|
|
Chronic Hepatitis C |
Drug: PSI-7977 Drug: BMS-790052 Drug: Ribavirin |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Parallel, Open-Label, Randomized Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of PSI-7977 in Combination With BMS-790052 With or Without Ribavirin in Treatment Naive Subjects Chronically Infected With Hepatitis C Virus Genotypes 1, 2, or 3 |
Resource links provided by NLM:
Further study details as provided by Bristol-Myers Squibb:
Primary Outcome Measures:
- Sustained Virologic Response (SVR) at post treatment week 24 defined by undetectable HCV RNA at 24 weeks post treatment. [ Time Frame: 24 weeks post treatment ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Frequency of deaths, SAEs, discontinuations due to AEs, and severity Grade 3/4 laboratory abnormalities. [ Time Frame: 24 Weeks post-treatment ] [ Designated as safety issue: Yes ]
- Maximum observed plasma concentration (Cmax) [ Time Frame: Day 7 and Day 14 ] [ Designated as safety issue: No ]Pharmacokinetics of BMS-790052, PSI-7977, and PSI-6206 will be derived from plasma concentration versus time data on Days 7 (PSI-7977 and PSI-6206 for subjects in treatment groups A and B only) and 14.
- Trough observed concentration (Cmin) [ Time Frame: Day 7 and Day 14 ] [ Designated as safety issue: No ]Pharmacokinetics of BMS-790052, PSI-7977, and PSI-6206 will be derived from plasma concentration versus time data on Days 7 (PSI-7977 and PSI-6206 for subjects in treatment groups A and B only) and 14.
- Time of maximum observed concentration (Tmax) [ Time Frame: Day 7 and Day 14 ] [ Designated as safety issue: No ]Pharmacokinetics of BMS-790052, PSI-7977, and PSI-6206 will be derived from plasma concentration versus time data on Days 7 (PSI-7977 and PSI-6206 for subjects in treatment groups A and B only) and 14.
- Area under the concentration-time curve in one dosing interval [AUC(TAU)] [ Time Frame: Day 7 and Day 14 ] [ Designated as safety issue: No ]Pharmacokinetics of BMS-790052, PSI-7977, and PSI-6206 will be derived from plasma concentration versus time data on Days 7 (PSI-7977 and PSI-6206 for subjects in treatment groups A and B only) and 14.
- Proportions of subjects who experience: rapid virologic response (RVR)[i.e, undetectable HCV ribonucleic acid (RNA) following 4 weeks of treatment] [ Time Frame: Screening, Days -1 (baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 9, Day 11, Day 14, Day 21, every 2 weeks from week 4 until end of treatment and at the Post-treatment 4 weeks, 12 weeks , 24 weeks, 36 weeks, 48 weeks ] [ Designated as safety issue: No ]
- Proportions of subjects who experience: extended rapid virologic response (eRVR)[i.e., undetectable HCV RNA following 4 and 12 weeks of treatment]. [ Time Frame: Screening, Days -1 (baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 9, Day 11, Day 14, Day 21, every 2 weeks from week 4 until end of treatment and at the Post-treatment 4 weeks, 12 weeks , 24 weeks, 36 weeks, 48 weeks ] [ Designated as safety issue: No ]
- Proportions of subjects who experience: complete early virologic response (cEVR) [i.e., undetectable HCV RNA following 12 weeks of treatment] [ Time Frame: Screening, Days -1 (baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 9, Day 11, Day 14, Day 21, every 2 weeks from week 4 until end of treatment and at the Post-treatment 4 weeks, 12 weeks , 24 weeks, 36 weeks, 48 weeks ] [ Designated as safety issue: No ]
- Proportions of subjects who experience: undetectable HCV RNA at end of treatment [ Time Frame: Screening, Days -1 (baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 9, Day 11, Day 14, Day 21, every 2 weeks from week 4 until end of treatment and at the Post-treatment 4 weeks, 12 weeks , 24 weeks, 36 weeks, 48 weeks ] [ Designated as safety issue: No ]
- Proportions of subjects who experience: sustained virologic response at post treatment week 12 (SVR12) [i.e., undetectable HCV RNA at 12 weeks post treatment] [ Time Frame: Screening, Days -1 (baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 9, Day 11, Day 14, Day 21, every 2 weeks from week 4 until end of treatment and at the Post-treatment 4 weeks, 12 weeks , 24 weeks, 36 weeks, 48 weeks ] [ Designated as safety issue: No ]
- Proportions of subjects who experience: Virologic breakthrough or relapse [ Time Frame: Screening, Days -1 (baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 9, Day 11, Day 14, Day 21, every 2 weeks from week 4 until end of treatment and at the Post-treatment 4 weeks, 12 weeks , 24 weeks, 36 weeks, 48 weeks ] [ Designated as safety issue: No ]
- Characterization of HCV genomic substitutions associated with exposure of BMS-790052 and PSI-7977 [ Time Frame: Screening, Days -1 (baseline), Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 9, Day 11, Day 14, Day 21, every 2 weeks from week 4 until end of treatment and at the Post-treatment 4 weeks, 12 weeks , 24 weeks, 36 weeks, 48 weeks ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 208 |
| Study Start Date: | June 2011 |
| Estimated Study Completion Date: | October 2013 |
| Estimated Primary Completion Date: | January 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment A: PSI-7977 + BMS-790052
PSI-7977 Once daily for 7 days then add once daily BMS-790052 Genotype 1a or 1b |
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
|
|
Experimental: Treatment B: PSI-7977 + BMS-790052
PSI-7977 Once daily for 7 days then add once daily BMS-790052. Genotype 2 or 3 |
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
|
|
Experimental: Treatment C: PSI-7977 + BMS-790052
Genotype 1a or 1b
|
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
|
|
Experimental: Treatment D: PSI-7977 + BMS-790052
Genotype 2 or 3
|
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
|
|
Experimental: Treatment E: PSI-7977 + BMS-790052 + Ribavirin
Genotype 1a or 1b
|
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
Drug: Ribavirin
Tablets, Oral, 200mg, For subjects weighing < 75 kg:1000 mg; for subjects weighing ≥ 75: 1200 mg, Twice daily < 75 kg: 400 mg in AM and 600 mg in PM; ≥ 75: 600 mg in AM and PM, 24 weeks
Other Name: Copegus ®
|
|
Experimental: Treatment F: PSI-7977 + BMS-790052 + Ribavirin
Genotype 2 or 3
|
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
Drug: Ribavirin
Tablets, Oral, 200mg, 400 mg (2 tablets) in AM and 400 mg (2 tablets) in PM, 24 weeks
Other Name: Copegus ®
|
|
Experimental: Treatment G: PSI-7977 + BMS-790052
HCV GT1 treatment naive subjects Genotype 1a or 1b |
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 12 weeks
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 12 weeks
|
|
Experimental: Treatment H: PSI-7977 + BMS-790052 + Ribavirin
HCV GT1 treatment naive subjects Genotype 1a or 1b |
Drug: Ribavirin
Tablets, Oral, 200mg, For subjects weighing < 75 kg:1000 mg; for subjects weighing ≥ 75: 1200 mg, Twice daily < 75 kg: 400 mg in AM and 600 mg in PM; ≥ 75: 600 mg in AM and PM, 12 weeks
Other Name: Copegus ®
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 12 weeks
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 12 weeks
|
|
Experimental: Treatment I: PSI-7977 + BMS-790052
Subjects who experienced Telaprevir (TVR)/Boceprevir (BOC) treatment failure Genotype 1a or 1b |
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
|
|
Experimental: Treatment J: PSI-7977 + BMS-790052 + Ribavirin
Subjects who experienced TVR/BOC Treatment failure Genotype 1a or 1b |
Drug: PSI-7977
Tablets, Oral, 400 mg, Once daily, 24 weeks
Drug: BMS-790052
Tablets, Oral, 60 mg, Once daily, 24 weeks
Drug: Ribavirin
Tablets, Oral, 200mg, For subjects weighing < 75 kg:1000 mg; for subjects weighing ≥ 75: 1200 mg, Twice daily < 75 kg: 400 mg in AM and 600 mg in PM; ≥ 75: 600 mg in AM and PM, 24 weeks
Other Name: Copegus ®
|
Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Male and female subjects ages 18 to 70 years.
- HCV-Infected Genotype 1, 2 or 3 subjects who have no previous exposure to an interferon formulation [ie interferon-alfa (IFNα), pegylated interferon-alfa (pegIFNα)], Ribavirin (RBV); or other HCV-specific direct acting antiviral (including BMS-790052 and PSI-7977).
- Subjects should have chronic hepatitis C (CHC) genotype 1a, 1b, 2, or 3 as documented by: i) Positive for anti-HCV antibody, HCV RNA, or a positive HCV genotype test at least 6 months prior to screening, and positive for HCV RNA and anti-HCV antibody at the time of screening.
Exclusion Criteria:
- Evidence of a medical condition associate with chronic liver disease other than HCV.
- History of variceal bleeding, hepatic encephalopathy, or ascites requiring management with diuretics or paracentesis.
- History of hemophilia.
- History of Torsade de pointes.
- Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment.
- History of gastrointestinal disease or surgical procedure (except Cholecystectomy).
- History of clinically significant cardiac disease.
- Blood transfusion within 4 weeks prior to study drug administration.
- Poor venous access.
- Any other medical, psychiatric and/or social reason which, in the opinion of the Investigator, would make the candidate inappropriate for participation in this study.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01359644
Locations
| United States, California | |
| Southern California Liver Centers | |
| Coronado, California, United States, 92118 | |
| Research And Education, Inc. | |
| San Diego, California, United States, 92105 | |
| Local Institution | |
| San Francisco, California, United States, 94143 | |
| United States, Colorado | |
| University Of Colorado Denver & Hospital | |
| Aurora, Colorado, United States, 80045 | |
| United States, Florida | |
| University Of Florida Hepatology | |
| Gainesville, Florida, United States, 32610 | |
| Orlando Immunology Center | |
| Orlando, Florida, United States, 32803 | |
| Miami Research Associates | |
| South Miami, Florida, United States, 33143 | |
| United States, Maryland | |
| Mercy Medical Center | |
| Baltimore, Maryland, United States, 21202 | |
| Johns Hopkins University | |
| Lutherville, Maryland, United States, 21093 | |
| United States, Michigan | |
| University Of Michigan Health System | |
| Ann Arbor, Michigan, United States, 48109 | |
| United States, New York | |
| Bronx Va Medical Center #111f | |
| Bronx, New York, United States, 10468 | |
| Weill Cornell Medical College | |
| New York, New York, United States, 10021 | |
| United States, Oklahoma | |
| Options Health Research, Llc | |
| Tulsa, Oklahoma, United States, 74104 | |
| Healthcare Research Consultants | |
| Tulsa, Oklahoma, United States, 74135 | |
| United States, Pennsylvania | |
| University Of Pennsylvania | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| United States, Texas | |
| Alamo Medical Research | |
| San Antonio, Texas, United States, 78215 | |
| United States, Virginia | |
| Metropolitan Research | |
| Fairfax, Virginia, United States, 22031 | |
| United States, Wisconsin | |
| Dean Clinic | |
| Madison, Wisconsin, United States, 53715 | |
| Puerto Rico | |
| Local Institution | |
| San Juan, Puerto Rico, 00927 | |
Sponsors and Collaborators
Bristol-Myers Squibb
Pharmasset
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
More Information
Additional Information:
No publications provided
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT01359644 History of Changes |
| Other Study ID Numbers: | AI444-040 |
| Study First Received: | May 23, 2011 |
| Last Updated: | July 11, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Hepatitis Hepatitis A Hepatitis, Chronic Hepatitis C Hepatitis C, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections |
Picornaviridae Infections RNA Virus Infections Flaviviridae Infections Ribavirin Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Antimetabolites Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 19, 2013