Phase III Hallmark QUAD: ASV+DCV+Peg+Rib (Nulls/Partials) - Full Text View

Purpose

The purpose of this study is to assess 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.

Condition	Intervention	Phase
Hepatitis C Virus	Drug: Asunaprevir Drug: Daclatasvir Drug: Peg-interferon Alfa-2a Drug: Ribavirin	Phase 3


Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 3, Open-Label Study With Asunaprevir and Daclatasvir Plus Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) (P/R) (QUAD) for Subjects Who Are Null or Partial Responders to Peginterferon Alfa 2a or 2b Plus Ribavirin With Chronic Hepatitis C Genotypes 1 or 4 Infection

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Interferon Ribavirin Interferon Alfa-2a Interferon Alfa-2b Peginterferon Alfa-2a Daclatasvir

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

Proportion of genotype 1 subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for all subjects infected with HCV genotype 1 [ Time Frame: At 12 weeks post-treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

On-treatment safety, as measured by frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) through the end of treatment [ Time Frame: Through the end of treatment (maximum up to 24 weeks) plus 7 days ] [ Designated as safety issue: Yes ]
Proportion of subjects with SVR12 (HCV RNA < LOQ at post-treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28 gene [ Time Frame: At post-treatment Week 12 ] [ Designated as safety issue: No ]
Proportion of subjects with HCV RNA undetectable [ Time Frame: Weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [Extended rapid virologic response (eRVR)], end of treatment (up to 24 weeks), post-treatment Week 12 or post-treatment Week 24 ] [ Designated as safety issue: No ]
Proportion of subjects with HCV RNA < LOQ [ Time Frame: Weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12, end of treatment (up to 24 weeks), post-treatment Week 24 (SVR24) ] [ Designated as safety issue: No ]
Proportion of patients with SVR12 (HCV RNA < LOQ at post-treatment Week 12) for HCV genotype 4 subjects [ Time Frame: Post-treatment Week 12 ] [ Designated as safety issue: No ]


Enrollment:	398
Study Start Date:	May 2012
Study Completion Date:	December 2013
Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: QUAD: Asunaprevir+Daclatasvir+Peg-interferon Alfa-2a+Ribavirin Asunaprevir: Capsule, Oral, 100 mg, Twice daily, 24 weeks Daclatasvir: Tablet, Oral, 60 mg, Once daily, 24 weeks Peg-interferon Alfa-2a: Injection, subcutaneous (SC), 180 mcg/0.5 mL, Once weekly, 24 weeks Ribavirin: Tablet, Oral, 1000 mg/1200 mg (total daily dose), 24 weeks	Drug: Asunaprevir Other Name: BMS-650032 Drug: Daclatasvir Other Name: BMS-790052 Drug: Peg-interferon Alfa-2a Other Name: Pegasys® Drug: Ribavirin Other Name: Copegus®

Detailed Description:

ASV = Asunaprevir (BMS-650032)
DCV = Daclatasvir (BMS-790052)
Peg = Peg-interferon Alfa-2a (PegIFN)
Rib = Ribavirin (RBV)

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Males and females, ≥ 18 years of age
HCV Genotype 1 or 4 who previously failed treatment with Peginterferon alfa-2a or peginterferon alfa-2b and Ribavirin (P/R), classified as previous null and partial responders based on previous therapy
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
Total bilirubin ≥ 34 μmol/L (or ≥ 2 mg/dL) unless subject has a documented history of Gilbert's disease
Alanine aminotransferase (ALT) ≥ 5x Upper limit of normal (ULN)
Albumin < 3.5 g/dL (35 g/L)
Alpha Fetoprotein (AFP) > 100 ng/mL (>82.6 IU/mL) or ≥ 50 and ≤ 100 ng/mL requires a liver ultrasound and subjects with findings suspicious of Hepatocellular carcinoma (HCC) are excluded
Absolute neutrophil count (ANC) < 1.5 x 1000,000,000 cells/L (< 1.2 x 1000,000,000 cells/L for Black/African-Americans)
Platelets < 90 x 1000,000,000 cells/L
Hemoglobin < 12 g/dL for females or < 13 g/dL for males
Any criteria that would exclude the subject from receiving P/R

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: NCT01573351

Show 79 Study Locations

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators


Study Director:	Bristol-Myers Squibb	Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trial Information This link exits the ClinicalTrials.gov site

BMS clinical trial educational resource This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Jensen D, Sherman KE, Hézode C, Pol S, Zeuzem S, de Ledinghen V, Tran A, Elkhashab M, Younes ZH, Kugelmas M, Mauss S, Everson G, Luketic V, Vierling J, Serfaty L, Brunetto M, Heo J, Bernstein D, McPhee F, Hennicken D, Mendez P, Hughes E, Noviello S; HALLMARK-QUAD Study Team. Daclatasvir and asunaprevir plus peginterferon alfa and ribavirin in HCV genotype 1 or 4 non-responders. J Hepatol. 2015 Jul;63(1):30-7. doi: 10.1016/j.jhep.2015.02.018. Epub 2015 Feb 19.


Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT01573351 History of Changes
Other Study ID Numbers:	AI447-029 2011-005422-21
Study First Received:	April 5, 2012
Last Updated:	September 23, 2015
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 Brazil: Ministry of Health 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 Switzerland: Swissmedic 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 Mexico: Federal Commission for Sanitary Risks Protection Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Denmark: Danish Dataprotection Agency Denmark: Danish Medicines Agency Denmark: The Danish National Committee on Biomedical Research Ethics Sweden: Medical Products Agency Sweden: The National Board of Health and Welfare Sweden: Swedish Data Inspection Board Sweden: Swedish National Council on Medical Ethics Italy: Ministry of Health Italy: National Bioethics Committee Italy: National Monitoring Centre for Clinical Trials - Ministry of Health Italy: The Italian Medicines Agency

Additional relevant MeSH terms:


Hepatitis C Hepatitis Hepatitis, Viral, Human Virus Diseases Flaviviridae Infections RNA Virus Infections Liver Diseases Digestive System Diseases Interferon-alpha Peginterferon alfa-2a	Interferons Ribavirin Antiviral Agents Anti-Infective Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 26, 2016

Phase III Hallmark QUAD: ASV+DCV+Peg+Rib (Nulls/Partials) (Hallmark QUAD)