Study of Daclatasvir and TMC435 for Subjects With Genotype 1 Chronic Hepatitis C
This study is ongoing, but not recruiting participants.
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: March 28, 2013
Last verified: February 2013
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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 ]
| Estimated Enrollment: | 180 |
| Study Start Date: | July 2012 |
| Estimated Study Completion Date: | November 2013 |
| Estimated 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01628692
Locations
| United States, California | |
| Kaiser Permanente Med Ctr | |
| San Francisco, California, United States, 94118 | |
| San Francisco General Hospital | |
| San Francisco, California, United States, 94110 | |
| 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, 1119 | |
| Local Institution | |
| Buenos Aires, Argentina, C1181ACH | |
| 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: | March 28, 2013 |
| 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 Publica 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 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