Phase III Hallmark DUAL: ASV+DCV (Nulls/Partials, Intolerants/Ineligibles. Naives)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01581203
First received: April 18, 2012
Last updated: July 23, 2014
Last verified: September 2013
  Purpose

The purpose of this study is to estimate efficacy, as determined by the proportion of subjects with Sustained virologic response at post-treatment Week 12 (SVR12), defined as Hepatitis C virus (HCV) Ribonucleic acid (RNA) < Limit of quantitation (LOQ) at post-treatment Week 12, for subjects who are prior null or partial responders to P/R or who are treatment-naive.


Condition Intervention Phase
Hepatitis C Virus
Drug: Asunaprevir (ASV)
Drug: Daclatasvir (DCV)
Drug: PBO matching ASV
Drug: PBO matching DCV
Drug: Pegylated-interferon alfa 2a (PegIFN)
Drug: Ribavirin (RBV)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Study With Asunaprevir and Daclatasvir (DUAL) for Null or Partial Responders to Peginterferon Alfa and Ribavirin (P/R), Intolerant or Ineligible to P/R Subjects and Treatment-Naive Subjects With Chronic Hepatitis C Genotype 1b Infection

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Proportion of treated subjects with SVR12, defined as HCV RNA < LOQ at post treatment Week 12, for subjects who are prior null or partial responders to P/R or are treatment-naive [ Time Frame: At 12 weeks post-treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of treated subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for subjects who are intolerant or ineligible to P/R [ Time Frame: Post-treatment Week 12 ] [ Designated as safety issue: No ]
  • On treatment safety, as measured by frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) [ Time Frame: End of Treatment (up to 48 weeks) plus 7 days ] [ Designated as safety issue: Yes ]
  • Differences in rates of selected grade 3-4 laboratory abnormalities during the first 12 weeks between treatments (ASV + DCV vs PBO) for naive subjects [ Time Frame: Up to first 12 weeks ] [ Designated as safety issue: No ]
  • Proportion of genotype 1b subjects with SVR12 (HCV RNA < LOQ at post treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28B gene for each cohort [ Time Frame: Post-treatment Week 12 ] [ Designated as safety issue: No ]
  • Proportion of genotype 1b subjects with HCV RNA undetectable [ Time Frame: At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [eRVR]; EOT (up to 24 weeks), post-treatment Week 12, or post-treatment Week 24 for each cohort ] [ Designated as safety issue: No ]
    eRVR = Extended rapid virologic response, EOT = End of treatment

  • Proportion of genotypes 1b subjects with HCV RNA < LOQ [ Time Frame: At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [VR(4&12)]; EOT (up to 24 weeks), post-treatment Week 24 (SVR24) for each cohort ] [ Designated as safety issue: No ]
  • Proportion of subjects with anemia [ Time Frame: At 12 weeks post-treatment ] [ Designated as safety issue: No ]
  • Proportion of subjects with rash [ Time Frame: At 12 weeks post-treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 725
Study Start Date: May 2012
Estimated Study Completion Date: September 2014
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Null or Partial Responder to P/R (ASV + DCV)

Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks

Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks

Drug: Asunaprevir (ASV)
Other Name: BMS-650032
Drug: Daclatasvir (DCV)
Other Name: BMS-790052
Experimental: Arm 2: Intolerant to or Ineligible for P/R (ASV + DCV)

Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks

Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks

Drug: Asunaprevir (ASV)
Other Name: BMS-650032
Drug: Daclatasvir (DCV)
Other Name: BMS-790052
Experimental: Arm 3: Treatment naive (ASV + DCV / Matching PBO)

[Subjects will receive ASV + DCV for 24 weeks] or [placebo (PBO) matching ASV + PBO matching DCV for 12 weeks followed by ASV + DCV for 24 weeks in protocol AI444026]

Subjects meeting prespecified rescue criteria in the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R)

Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks

Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks

PBO matching ASV 0 mg Capsule by mouth, Twice daily for 12 Weeks

Placebo (PBO) matching DCV 0 mg Tablet by mouth, Once daily for 12 Weeks

Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 weeks

Ribavirin 1000 mg / 1200 mg (depending on subject weight) Tablet by mouth, twice daily for 24 weeks

Drug: Asunaprevir (ASV)
Other Name: BMS-650032
Drug: Daclatasvir (DCV)
Other Name: BMS-790052
Drug: PBO matching ASV Drug: PBO matching DCV Drug: Pegylated-interferon alfa 2a (PegIFN)
Other Name: Pegasys
Drug: Ribavirin (RBV)
Other Name: Copegus
Experimental: Arm 4: Null or Partial Responder to P/R (ASV + DCV) 24/48 week

Subjects meeting prespecified rescue criteria in the null or partial responder cohort or active arm of the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R)

Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks

Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks

Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks

Ribavirin 1000 mg / 1200 mg (depending on subject weight) Tablet by mouth, twice daily for 24 or 48 weeks

Drug: Asunaprevir (ASV)
Other Name: BMS-650032
Drug: Daclatasvir (DCV)
Other Name: BMS-790052
Drug: Pegylated-interferon alfa 2a (PegIFN)
Other Name: Pegasys
Drug: Ribavirin (RBV)
Other Name: Copegus

Detailed Description:

Allocation: Treatment naive cohort: Randomized Controlled Trial, Null/partial responder and intolerant/ineligible cohorts: N/A (Single arm study)

Masking: Treatment naive cohort: Double Blind, Null/partial responder and intolerant/ineligible cohorts: Open

Intervention Model: Treatment naive cohort: Parallel, Null/partial responder and intolerant/ineligible cohorts: Single group

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females, ≥ 18 years of age
  • HCV Genotype 1b who previously failed treatment with peginterferon alfa and ribavirin, classified as previous null or partial responders based on previous therapy, OR intolerant or ineligible to P/R due to neutropenia, anemia, depression or thrombocytopenia with cirrhosis, OR treatment naive
  • HCV RNA ≥ 10,000 IU/mL
  • Seronegative for Human immunodeficiency virus (HIV) and Hepatitis B surface antigen (HBsAg)
  • Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped at approximately 25% of treated population)

Exclusion Criteria:

  • Prior treatment of HCV with HCV direct acting antiviral (DAA)
  • Evidence of a medical condition contributing to chronic liver disease other than HCV
  • Evidence of decompensated liver disease including, but not limited to, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
  • Diagnosed or suspected hepatocellular carcinoma or other malignancies
  • Uncontrolled diabetes or hypertension
  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: NCT01581203

  Show 116 Study Locations
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: NCT01581203     History of Changes
Other Study ID Numbers: AI447-028, 2011-005446-35
Study First Received: April 18, 2012
Last Updated: July 23, 2014
Health Authority: United States: Food and Drug Administration
Korea: Food and Drug Administration
Taiwan: Department of Health
Taiwan: National Bureau of Controlled Drugs
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: National Health and Medical Research Council
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Canada: Health Canada
Russia: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Russia: FSI Scientific Center of Expertise of Medical Application
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
Singapore: Clinical Trials & Epidemiology Research Unit (CTERU)
New Zealand: Medsafe
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
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
Ireland: Irish Medicines Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Israel: Israeli Health Ministry Pharmaceutical Administration
Poland: National Institute of Medicines
Poland: Ministry of Health
Poland: Ministry of Science and Higher Education
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Brazil: National Health Surveillance Agency
Brazil: National Committee of Ethics in Research

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferon-alpha
Interferon Alfa-2a
Interferons
Ribavirin
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2014