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

NCT ID: NCT01581203

Last Updated: 2015-10-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

748 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-05-31

Study Completion Date

2014-09-30

Brief Summary

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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.

Detailed Description

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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

Conditions

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Hepatitis C Virus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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

Group Type EXPERIMENTAL

Asunaprevir (ASV)

Intervention Type DRUG

Daclatasvir (DCV)

Intervention Type DRUG

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

Group Type EXPERIMENTAL

Asunaprevir (ASV)

Intervention Type DRUG

Daclatasvir (DCV)

Intervention Type DRUG

Arm 3: Treatment naive (ASV + DCV)

\[Subjects will receive ASV + DCV for 24 weeks\] 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 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 (total daily dose) tablet by mouth for 24 or 48 weeks

Group Type EXPERIMENTAL

Asunaprevir (ASV)

Intervention Type DRUG

Daclatasvir (DCV)

Intervention Type DRUG

Pegylated-interferon alfa 2a (PegIFN)

Intervention Type DRUG

Ribavirin (RBV)

Intervention Type DRUG

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 (total daily dose) Tablet by mouth, for 24 or 48 weeks

Group Type EXPERIMENTAL

Asunaprevir (ASV)

Intervention Type DRUG

Daclatasvir (DCV)

Intervention Type DRUG

Pegylated-interferon alfa 2a (PegIFN)

Intervention Type DRUG

Ribavirin (RBV)

Intervention Type DRUG

Interventions

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Asunaprevir (ASV)

Intervention Type DRUG

Daclatasvir (DCV)

Intervention Type DRUG

Pegylated-interferon alfa 2a (PegIFN)

Intervention Type DRUG

Ribavirin (RBV)

Intervention Type DRUG

Other Intervention Names

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BMS-650032 BMS-790052 Pegasys Copegus

Eligibility Criteria

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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 fibrosis/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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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The Health Care Authority For Baptist Health

Montgomery, Alabama, United States

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Scripps Clinic

La Jolla, California, United States

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Scpmg/ Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

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University Of Colorado Denver And Hospital

Aurora, Colorado, United States

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Uf Hepatology Research At Ctrb

Gainesville, Florida, United States

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Johns Hopkins Medical Institutions

Lutherville, Maryland, United States

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Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

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Henry Ford Health System

Detroit, Michigan, United States

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Washington University School Of Medicine

St Louis, Missouri, United States

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North Shore-Long Island Jewish Health System

Manhasset, New York, United States

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Weill Cornell Medical College

New York, New York, United States

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University Of North Carolina At Chapel Hill School Of Med

Chapel Hill, North Carolina, United States

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Carolinas Medical Center

Charlotte, North Carolina, United States

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Duke University Medical Center

Durham, North Carolina, United States

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Baylor College Of Medicine

Houston, Texas, United States

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Vamc

Houston, Texas, United States

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Alamo Medical Research

San Antonio, Texas, United States

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Dean Clinic

Madison, Wisconsin, United States

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Local Institution

Buenos Aires, Buenos Aires, Argentina

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Ciudad de Buenos Aires, Buenos Aires, Argentina

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Prov de Santa Fe, Santa Fe Province, Argentina

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Darlinghurst, New South Wales, Australia

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Kogarah, New South Wales, Australia

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Randwick, New South Wales, Australia

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Fitzroy, Queensland, Australia

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Adelaide, South Australia, Australia

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Bedford Park, Sa, South Australia, Australia

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Clayton, Victoria, Australia

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Heidelberg, Victoria, Australia

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Melbourne, Victoria, Australia

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Fremantle, Western Australia, Australia

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Nedlands, Western Australia, Australia

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Perth, Western Australia, Australia

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Graz, , Austria

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Linz, , Austria

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Salzburg, , Austria

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Vienna, , Austria

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Vienna, , Austria

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Gastrointestinal Research Institute (G.I.R.I.)

Vancouver, British Columbia, Canada

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Percuro Clinical Research Ltd

Victoria, British Columbia, Canada

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Toronto General Hospital-University Health Network

Toronto, Ontario, Canada

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Toronto Liver Centre

Toronto, Ontario, Canada

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Toronto Digestive Disease Associates, Inc.

Vaughan, Ontario, Canada

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Clinique Medicale Lactuel

Montreal, Quebec, Canada

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Jewish General Hospital

Montreal, Quebec, Canada

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Alpha-Recherche Clinique

Québec, Quebec, Canada

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Clichy, , France

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Créteil, , France

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Lyon, , France

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Marseille, , France

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Paris, , France

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Paris, , France

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Toulouse, , France

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Vandœuvre-lès-Nancy, , France

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Berlin, , Germany

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Berlin, , Germany

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Bonn, , Germany

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Essen, , Germany

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Frankfurt, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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München, , Germany

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Dublin, Dublin, Ireland

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Dublin, Dublin, Ireland

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Haifa, , Israel

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Jerusalem, , Israel

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Jerusalem, , Israel

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Tel Aviv, , Israel

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Tel Litwinsky, , Israel

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Zafed, , Israel

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Messina, , Italy

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Milan, , Italy

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Roma, , Italy

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Torino, , Italy

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Amsterdam, , Netherlands

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Leiden, , Netherlands

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Rotterdam, , Netherlands

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Auckland, , New Zealand

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Hamilton, , New Zealand

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Wellington, , New Zealand

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Bialystok, , Poland

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Wroclaw, , Poland

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Chelyabinsk, , Russia

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Krasnoyarsk, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Samara, , Russia

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Smolensk, , Russia

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Tyumen, , Russia

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Busan, , South Korea

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Busan, , South Korea

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Busan, , South Korea

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Daegu, , South Korea

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Daegu, , South Korea

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Gyeonggi-do, , South Korea

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Gyeongsangnam-do, , South Korea

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Incheon, , South Korea

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Incheon, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Alicante, , Spain

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Barcelona, , Spain

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Madrid, , Spain

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Valencia, , Spain

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Taichung, , Taiwan

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Taichung, , Taiwan

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Tainan City, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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London, Greater London, United Kingdom

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London, Greater London, United Kingdom

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Manchester, Greater Manchester, United Kingdom

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Glasgow, Lanarkshire, United Kingdom

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Countries

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United States Argentina Australia Austria Canada France Germany Ireland Israel Italy Netherlands New Zealand Poland Russia South Korea Spain Taiwan United Kingdom

References

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Kao JH, Lee YJ, Heo J, Ahn SH, Lim YS, Peng CY, Chang TT, Torbeyns A, Hughes E, Bhore R, Noviello S. All-oral daclatasvir plus asunaprevir for chronic hepatitis C virus (HCV) genotype 1b infection: a sub-analysis in Asian patients from the HALLMARK DUAL study. Liver Int. 2016 Oct;36(10):1433-41. doi: 10.1111/liv.13128. Epub 2016 Apr 28.

Reference Type DERIVED
PMID: 27009831 (View on PubMed)

Kao JH, Jensen DM, Manns MP, Jacobson I, Kumada H, Toyota J, Heo J, Yoffe B, Sievert W, Bessone F, Peng CY, Roberts SK, Lee YJ, Bhore R, Mendez P, Hughes E, Noviello S. Daclatasvir plus asunaprevir for HCV genotype 1b infection in patients with or without compensated cirrhosis: a pooled analysis. Liver Int. 2016 Jul;36(7):954-62. doi: 10.1111/liv.13049. Epub 2016 Jan 24.

Reference Type DERIVED
PMID: 26683763 (View on PubMed)

Manns M, Pol S, Jacobson IM, Marcellin P, Gordon SC, Peng CY, Chang TT, Everson GT, Heo J, Gerken G, Yoffe B, Towner WJ, Bourliere M, Metivier S, Chu CJ, Sievert W, Bronowicki JP, Thabut D, Lee YJ, Kao JH, McPhee F, Kopit J, Mendez P, Linaberry M, Hughes E, Noviello S; HALLMARK-DUAL Study Team. All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study. Lancet. 2014 Nov 1;384(9954):1597-605. doi: 10.1016/S0140-6736(14)61059-X. Epub 2014 Jul 28.

Reference Type DERIVED
PMID: 25078304 (View on PubMed)

Related Links

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Other Identifiers

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2011-005446-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AI447-028

Identifier Type: -

Identifier Source: org_study_id

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