Clinical trial NCT01581203: Phase III Hallmark DUAL: ASV+DCV (Nulls/Partials, Intolerants/Ineligibles. Naives)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C Virus
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2012-04-20
Enrollment: 748
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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 criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

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

Primary outcomes:
measure: 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
timeFrame: At 12 weeks post-treatment
Secondary outcomes:
measure: 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
timeFrame: Post-treatment Week 12
measure: On treatment safety, as measured by frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs)
timeFrame: End of Treatment (up to 48 weeks) plus 7 days
measure: Differences in rates of selected grade 3-4 laboratory abnormalities during the first 12 weeks between treatments (ASV + DCV vs PBO) for naive subjects
timeFrame: Up to first 12 weeks
measure: 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
timeFrame: Post-treatment Week 12
measure: Proportion of genotype 1b subjects with HCV RNA undetectable
timeFrame: 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
measure: Proportion of genotypes 1b subjects with HCV RNA < LOQ
timeFrame: 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
measure: Proportion of subjects with anemia
timeFrame: At 12 weeks post-treatment
measure: Proportion of subjects with rash
timeFrame: At 12 weeks post-treatment
Other outcomes:
Locations:
city: Montgomery
country: United States
facility: The Health Care Authority For Baptist Health
state: Alabama
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: Scpmg/ Kaiser Permanente Los Angeles Medical Center
state: California
city: Aurora
country: United States
facility: University Of Colorado Denver And Hospital
state: Colorado
city: Gainesville
country: United States
facility: Uf Hepatology Research At Ctrb
state: Florida
city: Lutherville
country: United States
facility: Johns Hopkins Medical Institutions
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Manhasset
country: United States
facility: North Shore-Long Island Jewish Health System
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Chapel Hill
country: United States
facility: University Of North Carolina At Chapel Hill School Of Med
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Houston
country: United States
facility: Baylor College Of Medicine
state: Texas
city: Houston
country: United States
facility: Vamc
state: Texas
city: San Antonio
country: United States
facility: Alamo Medical Research
state: Texas
city: Madison
country: United States
facility: Dean Clinic
state: Wisconsin
city: Ciudad De Buenos Aires
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Prov De Santa Fe
country: Argentina
facility: Local Institution
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Darlinghurst
country: Australia
facility: Local Institution
state: New South Wales
city: Kogarah
country: Australia
facility: Local Institution
state: New South Wales
city: Randwick
country: Australia
facility: Local Institution
state: New South Wales
city: Fitzroy
country: Australia
facility: Local Institution
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution
state: South Australia
city: Bedford Park, Sa
country: Australia
facility: Local Institution
state: South Australia
city: Clayton
country: Australia
facility: Local Institution
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution
state: Victoria
city: Melbourne
country: Australia
facility: Local Institution
state: Victoria
city: Fremantle
country: Australia
facility: Local Institution
state: Western Australia
city: Nedlands
country: Australia
facility: Local Institution
state: Western Australia
city: Perth
country: Australia
facility: Local Institution
state: Western Australia
city: Graz
country: Austria
facility: Local Institution
city: Linz
country: Austria
facility: Local Institution
city: Salzburg
country: Austria
facility: Local Institution
city: Wien
country: Austria
facility: Local Institution
city: Wien
country: Austria
facility: Local Institution
city: Vancouver
country: Canada
facility: Gastrointestinal Research Institute (G.I.R.I.)
state: British Columbia
city: Victoria
country: Canada
facility: Percuro Clinical Research Ltd
state: British Columbia
city: Toronto
country: Canada
facility: Toronto General Hospital-University Health Network
state: Ontario
city: Toronto
country: Canada
facility: Toronto Liver Centre
state: Ontario
city: Vaughan
country: Canada
facility: Toronto Digestive Disease Associates, Inc.
state: Ontario
city: Montreal
country: Canada
facility: Clinique Medicale Lactuel
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Quebec
country: Canada
facility: Alpha-Recherche Clinique
city: Clichy Cedex
country: France
facility: Local Institution
city: Creteil
country: France
facility: Local Institution
city: Lyon Cedex 04
country: France
facility: Local Institution
city: Marseille Cedex 08
country: France
facility: Local Institution
city: Paris Cedex 13
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Toulouse
country: France
facility: Local Institution
city: Vandoeuvre Les Nancy
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Bonn
country: Germany
facility: Local Institution
city: Essen
country: Germany
facility: Local Institution
city: Frankfurt
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Hannover
country: Germany
facility: Local Institution
city: Muenchen
country: Germany
facility: Local Institution
city: Dublin
country: Ireland
facility: Local Institution
city: Dublin
country: Ireland
facility: Local Institution
city: Haifa
country: Israel
facility: Local Institution
city: Jerusalem
country: Israel
facility: Local Institution
city: Jerusalem
country: Israel
facility: Local Institution
city: Tel Aviv
country: Israel
facility: Local Institution
city: Tel Hashomer
country: Israel
facility: Local Institution
city: Zafed
country: Israel
facility: Local Institution
city: Messina
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Torino
country: Italy
facility: Local Institution
city: Busan
country: Korea, Republic of
facility: Local Institution
city: Busan
country: Korea, Republic of
facility: Local Institution
city: Busan
country: Korea, Republic of
facility: Local Institution
city: Daegu
country: Korea, Republic of
facility: Local Institution
city: Daegu
country: Korea, Republic of
facility: Local Institution
city: Gyeonggi-do
country: Korea, Republic of
facility: Local Institution
city: Gyeongsangnam-do
country: Korea, Republic of
facility: Local Institution
city: Incheon
country: Korea, Republic of
facility: Local Institution
city: Incheon
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Amsterdam
country: Netherlands
facility: Local Institution
city: Leiden
country: Netherlands
facility: Local Institution
city: Rotterdam
country: Netherlands
facility: Local Institution
city: Auckland
country: New Zealand
facility: Local Institution
city: Hamilton
country: New Zealand
facility: Local Institution
city: Wellington
country: New Zealand
facility: Local Institution
city: Bialystok
country: Poland
facility: Local Institution
city: Wroclaw
country: Poland
facility: Local Institution
city: Chelyabinsk
country: Russian Federation
facility: Local Institution
city: Krasnoyarsk
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Saint-Petersburg
country: Russian Federation
facility: Local Institution
city: Samara
country: Russian Federation
facility: Local Institution
city: Smolensk
country: Russian Federation
facility: Local Institution
city: Tyumen
country: Russian Federation
facility: Local Institution
city: Alicante
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Valencia
country: Spain
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Tainan
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: Manchester
country: United Kingdom
facility: Local Institution
state: Greater Manchester
city: Glasgow
country: United Kingdom
facility: Local Institution
state: Lanarkshire
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.