Study of Daclatasvir and TMC435 for Subjects With Genotype 1 Chronic Hepatitis C
This study has been completed.
Sponsor:
Bristol-Myers Squibb
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01628692
First received: June 25, 2012
Last updated: May 5, 2014
Last verified: May 2014
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Purpose
The purpose of this study is to assess the safety and efficacy of Daclatasvir and TMC435 with and without Ribavirin for genotype 1 chronic hepatitis C in subjects who are treatment-naive or null responders to previous Peginterferon/Ribavirin therapy.
| Condition | Intervention | Phase |
|---|---|---|
|
Hepatitis C Virus |
Drug: Daclatasvir (DCV) Drug: TMC435 Drug: Ribavirin Biological: pegIFNα-2a |
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: | A Phase 2, Open-Label Study of Daclatasvir (BMS-790052) and TMC435 in Combination With or Without Ribavirin (RBV) For Treatment-Naive Subjects or Null Responders to Prior Peginterferon Alfa (PegIFN)/RBV Therapy With Genotype 1 Chronic Hepatitis C |
Resource links provided by NLM:
Further study details as provided by Bristol-Myers Squibb:
Primary Outcome Measures:
- Antiviral activity, as determined by the proportion of subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for each cohort defined by the previous response status, HCV genotype, initial treatment regimen and treatment duration [ Time Frame: Post treatment Week 12 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- On-treatment safety, as measured by the frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) [ Time Frame: Up to 24 weeks plus 7 days ] [ Designated as safety issue: Yes ]
- Proportion of subjects with Sustained virologic response12 (SVR12) (HCV RNA < LOQ at post-treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28B gene for each treatment arm [ Time Frame: Post treatment week 12 ] [ Designated as safety issue: No ]
- Proportion of subjects with Hepatitis C virus (HCV) Ribonucleic acid (RNA) < Limit of quantitation (LOQ) [ Time Frame: Weeks 1, 2, 4, 6, and 8 (and 12); EOT (End of treatment) (up to 24 weeks), post-treatment Week 24 (SVR24) for each treatment arm, and post-treatment Week 36 (genotype 1b) for subjects in the 12 week treatment arms ] [ Designated as safety issue: No ]
- Proportion of subjects with HCV RNA undetectable [ Time Frame: Weeks 1, 2, 4, 6, and 8 (and 12); EOT (up to 24 weeks), post-treatment Week 12 and post-treatment Week 24 for each treatment arm, and post-treatment Week 36 (genotype 1b) for subjects in the 12 week treatment arms ] [ Designated as safety issue: No ]
| Enrollment: | 168 |
| Study Start Date: | July 2012 |
| Study Completion Date: | November 2013 |
| Primary Completion Date: | August 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Cohort 1 Genotype 1b: DCV + TMC435
Potential additional treatment if criteria met with Peginterferon Alfa-2a, (pegIFNα-2a) and Ribavirin (RBV) 12 weeks. Subjects who complete Week 12 will undergo a second randomization (1:1 allocation) to stop treatment and enter a 36 week post treatment phase or to continue treatment through Week 24 and enter a 24 week post treatment phase There is a potential for additional treatment for an additional 24 weeks during subjects treatment phase depending on criteria |
Drug: Daclatasvir (DCV)
Tablets, Oral, 30 mg, once daily (QD), 12 or 24 weeks
Other Name: BMS-790052
Drug: TMC435
Capsule, Oral, 150 mg, QD, 12 or 24 weeks
Drug: Ribavirin
Tablets, Oral, 500-600 mg, twice daily, 24 weeks
Biological: pegIFNα-2a
Solution, Injection, 180 μg, Once a week, 24 weeks
|
|
Experimental: Cohort 2 Genotype 1b: DCV + TMC435 + RBV
Potential additional treatment if criteria met: Peginterferon Alfa-2a. (pegIFNα-2a) 12 weeks. Subjects who complete Week 12 will undergo a second randomization (1:1 allocation) to stop treatment and enter a 36 week post treatment phase or to continue treatment through Week 24 and enter a 24 week post treatment phase There is a potential for additional treatment for an additional 24 weeks during subjects treatment phase depending on criteria |
Drug: Daclatasvir (DCV)
Tablets, Oral, 30 mg, once daily (QD), 12 or 24 weeks
Other Name: BMS-790052
Drug: TMC435
Capsule, Oral, 150 mg, QD, 12 or 24 weeks
Drug: Ribavirin
Tablets, Oral, 500-600 mg, twice daily, 12 or 24 weeks
Biological: pegIFNα-2a
Solution, Injection, 180 μg, Once a week, 24 weeks
|
|
Experimental: Cohort 3 Genotype 1a: DCV + TMC435 + RBV
Potential additional treatment if criteria met: Peginterferon Alfa-2a, (pegIFNα-2a) 24 weeks. Subjects after 24 weeks will enter a 24 week post treatment phase There is a potential for additional treatment for an additional 24 weeks during subjects treatment phase depending on criteria |
Drug: Daclatasvir (DCV)
Tablets, Oral, 30 mg, QD, 24 weeks
Other Name: BMS-790052
Drug: TMC435
Capsule, Oral, 150 mg, QD, 24 weeks
Drug: Ribavirin
Tablets, Oral, 500-600 mg, twice daily, 24 weeks
Biological: pegIFNα-2a
Solution, Injection, 180 μg, Once a week, 24 weeks
|
|
Experimental: Cohort 4 Genotype 1a: DCV+TMC435+RBV
Potential additional treatment if criteria met: Peginterferon Alfa-2a, (pegIFNα-2a) 12 weeks. Subjects after 12 weeks will enter a 24 week post treatment phase. There is a potential for additional treatment for an additional 24 weeks during subjects treatment phase depending on criteria |
Drug: Daclatasvir (DCV)
Tablets, Oral, 30 mg, once daily (QD), 12 weeks
Other Name: BMS-790052
Drug: TMC435
Capsule, Oral, 150 mg, QD, 12 weeks
Drug: Ribavirin
Tablets, Oral, 500-600 mg, twice daily, 12 weeks
Biological: pegIFNα-2a
Solution, Injection, 180 μg, Once a week, 24 weeks
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- HCV Genotype 1a or 1b
- Males and females, ≥ 18 years of age
- HCV RNA ≥ 10,000 IU/mL
-
Subjects with compensated cirrhosis are permitted
- Advanced fibrosis (F3/F4) is capped at approximately 35% of the total treated population with a minimum of 20% F4 subjects
- If no cirrhosis, a liver biopsy within 3 years prior to enrollment is required
- If cirrhosis is present, any prior liver biopsy is sufficient
Exclusion Criteria:
Target Disease Exceptions
- Liver or any other transplant (other than cornea and hair)
- Evidence of a medical condition contributing to chronic liver disease other than HCV
- 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
- Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
- Subjects infected with Human immunodeficiency virus (HIV) or Hepatitis B virus (HBV)
- Gastrointestinal disease impacting absorption of study drug
- Uncontrolled diabetes or hypertension
Medication related
- Prior exposure to an HCV direct acting agent (DAA)
- Any criteria that would exclude the subject from receiving Ribavirin (RBV)
Exclusion Laboratory results
- Absolute neutrophil count (ANC) < 1.5 x 1,000,000,000 cells/L (<1.2 x 1,000,000,000 cells/L for Black/African-Americans)
- Platelets < 90 x 1,000,000,000 cells/L
- Hemoglobin < 12 g/dL for females or < 13 g/dL for males
- Alanine aminotransferase (ALT) ≥ 5 x Upper limit of normal (ULN)
- In subjects without cirrhosis, total bilirubin ≥ 34 μmol/L (or ≥ 2 mg/dL) unless subject has a documented history of Gilbert's disease
- In subjects with cirrhosis, total bilirubin ≥ 26 μmol/L (or ≥ 1.5 mg/dL)
- International normalized ratio (INR) ≥ 1.7
- QTcF or QTcB > 500 mSec
- Creatinine Clearance (CrCl) ≤ 50 mL/min
- Alpha Fetoprotein (AFP) > 100 ng/mL OR
- AFP ≥ 50 ng/mL and ≤ 100 ng/mL requires a liver ultrasound [Hepatocellular carcinoma (HCC) are excluded]
- Albumin < 3.5 g/dL (35 g/L)
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01628692
Please refer to this study by its ClinicalTrials.gov identifier: NCT01628692
Locations
| United States, California | |
| San Francisco General Hospital | |
| San Francisco, California, United States, 94110 | |
| Kaiser Permanente Med Ctr | |
| San Francisco, California, United States, 94118 | |
| United States, Indiana | |
| Indiana University | |
| Indianapolis, Indiana, United States, 46202 | |
| United States, Maryland | |
| Johns Hopkins University | |
| Lutherville, Maryland, United States, 21093 | |
| United States, Tennessee | |
| Nashville Medical Research Institute | |
| Nashville, Tennessee, United States, 37205 | |
| United States, Texas | |
| Texas Clinical Research Institute, Llc | |
| Arlington, Texas, United States, 76012 | |
| United States, Virginia | |
| Metropolitan Research | |
| Fairfax, Virginia, United States, 22031 | |
| Argentina | |
| Local Institution | |
| Buenos Aires, Argentina, C1181ACH | |
| Local Institution | |
| Buenos Aires, Argentina, 1119 | |
| France | |
| Local Institution | |
| Creteil Cedex, France, 94010 | |
| Local Institution | |
| Limoges, France, 87042 | |
| Local Institution | |
| Marseille Cedex 08, France, 13285 | |
| Local Institution | |
| Paris Cedex 13, France, 75651 | |
| Local Institution | |
| Paris Cedex 14, France, 75679 | |
| Local Institution | |
| Pessac, France, 33600 | |
| Local Institution | |
| Vandoeuvre Les Nancy, France, 54511 | |
| Germany | |
| Local Institution | |
| Berlin, Germany, 10969 | |
| Local Institution | |
| Frankfurt, Germany, 60590 | |
| Local Institution | |
| Hamburg, Germany, 20099 | |
| Local Institution | |
| Koeln, Germany, 50937 | |
| Hungary | |
| Local Institution | |
| Budapest, Hungary, 1097 | |
| Local Institution | |
| Budapest, Hungary, 1126 | |
| Local Institution | |
| Gyula, Hungary, 5700 | |
| Spain | |
| Local Institution | |
| Barcelona, Spain, 08035 | |
| Local Institution | |
| Madrid, Spain, 28046 | |
| Local Institution | |
| Valencia, Spain, 46010 | |
Sponsors and Collaborators
Bristol-Myers Squibb
Janssen Research & Development, LLC
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
More Information
Additional Information:
No publications provided
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT01628692 History of Changes |
| Other Study ID Numbers: | AI444-062, 2012-000070-28 |
| Study First Received: | June 25, 2012 |
| Last Updated: | May 5, 2014 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board Russia: Ethics Committee Russia: Ministry of Health of the Russian Federation Russia: FSI Scientific Center of Expertise of Medical Application Hungary: National Institute of Pharmacy Chile: Instituto de Salud Pública de Chile Germany: Federal Institute for Drugs and Medical Devices Germany: Ministry of Health France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Spain: Spanish Agency of Medicines Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica |
Additional relevant MeSH terms:
|
Hepatitis C Digestive System Diseases Flaviviridae Infections Hepatitis Hepatitis, Viral, Human Liver Diseases RNA Virus Infections Virus Diseases |
Ribavirin Anti-Infective Agents Antimetabolites Antiviral Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Therapeutic Uses |
ClinicalTrials.gov processed this record on March 03, 2015