BMS to start Ph3 study of BMS-791325(NS5B)+DCV+ASV FDC with or w/o RBV in GT1 HCV

A Study of an Investigational Treatment Regimen of Daclatasvir(DCV)+Asunaprevir(ASV)+BMS-791325 in a Fixed Dose Combination(the Triple Regimen)With or Without Ribavirin(RBV)for 12 Weeks for the Treatment of Chronic Hepatitis C Virus(HCV)Genotype 1 Infection in Subjects With Compensated Cirrhosis

This study is not yet open for participant recruitment.

Verified October 2013 by Bristol-Myers Squibb

Sponsor: Bristol-Myers Squibb

Information provided by (Responsible Party): Bristol-Myers Squibb

ClinicalTrials.gov Identifier: NCT01973049
First received: October 25, 2013
Last updated: October 30, 2013
Last verified: October 2013
History of Changes

Purpose

To demonstrate the effectiveness of Triple fixed dose combination with or without Ribavirin in treatment naive cirrhotic subjects.

Condition	Intervention	Phase
Hepatitis C Virus	Drug: Daclatasvir Drug: Asunaprevir Drug: BMS-791325 Drug: Ribavirin Drug: Placebo matching Ribavirin	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	A Phase 3 Evaluation of a Daclatasvir/Asunaprevir/BMS-791325 Fixed Dose Combination in Subjects With Genotype 1 Chronic Hepatitis C and Compensated Cirrhosis

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

• Proportion of treated subjects in each of the naive arms with sustained virologic response (SVR12) [ Time Frame: Post treatment 12 week ] [ Designated as safety issue: No ]

  SVR12 is defined as Hepatitis C virus ribonucleic acid (HCV RNA) < Limit of Quantification (LOQ) target detected or target not detected (LOQ TD/TND)

Secondary Outcome Measures:

• Proportion of treated subjects in each of the experienced arms with SVR12 [ Time Frame: Post treatment 12 Week ] [ Designated as safety issue: No ]
• Proportion of subjects in each arm who achieve HCV RNA < LOQ TD/TND [ Time Frame: Weeks: 1, 2, 4, 6, 8, and 12; Post treatment Weeks 4 (SVR4), 8 (SVR8) and 24 (SVR24) ] [ Designated as safety issue: No ]
• Proportion of subjects in each arm who achieve HCV RNA < LOQ TND [ Time Frame: Weeks: 1, 2, 4, 6, 8, and 12; Post treatment Weeks 4 (SVR4), 8 (SVR8), 12 (SVR12) and 24 (SVR24) ] [ Designated as safety issue: No ]
• Safety as measured by frequency of Serious Adverse Events(SAEs)and discontinuations due to Adverse Events(AEs) [ Time Frame: Up to end of treatment (week 12) + 7 days ] [ Designated as safety issue: Yes ]
• Proportion of subjects with anemia defined as Haemoglobin(Hg) < 10 g/dL Events(AEs) [ Time Frame: Up to end of treatment (week 12) + 7 days ] [ Designated as safety issue: Yes ]
• Differences in rates of selected Grade 3 - 4 laboratory test result abnormalities [ Time Frame: Up to end of treatment (week 12) + 7 days ] [ Designated as safety issue: Yes ]
• Proportion of subjects achieving SVR12 associated with HCV geno subtype 1a vs 1b [ Time Frame: Post treatment 12 Week ] [ Designated as safety issue: No ]
• Proportion of subjects in each arm achieving SVR12 associated with IL28B rs12979860 single nucleotide polymorphism(SNP) status (CC genotype or non-CC genotype) [ Time Frame: Post treatment 12 Week ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: December 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A1: DCV/ASV/BMS-791325+Placebo matching RBV (naive) Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Placebo matching Ribavirin 0mg tablet orally twice a day for 12 weeks	Drug: Daclatasvir Other Name: BMS-790052 Drug: Asunaprevir Other Name: BMS-650032 Drug: BMS-791325 Drug: Placebo matching Ribavirin
Experimental: A2: DCV/ASV/BMS-791325 + RBV (naive) Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Ribavirin 200mg tablet orally twice a day for 12 weeks	Drug: Daclatasvir Other Name: BMS-790052 Drug: Asunaprevir Other Name: BMS-650032 Drug: BMS-791325 Drug: Ribavirin Other Name: Ribasphere®
Experimental: A3: DCV/ASV/BMS-791325+Placebo matching RBV (experienced) Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Placebo matching Ribavirin 0 mg tablet orally twice a day for 12 weeks	Drug: Daclatasvir Other Name: BMS-790052 Drug: Asunaprevir Other Name: BMS-650032 Drug: BMS-791325 Drug: Placebo matching Ribavirin
Experimental: A4: DCV/ASV/BMS-791325 + RBV (experienced) Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Ribavirin 200mg tablet orally twice a day for 12 weeks	Drug: Daclatasvir Other Name: BMS-790052 Drug: Asunaprevir Other Name: BMS-650032 Drug: BMS-791325 Drug: Ribavirin Other Name: Ribasphere®

Detailed Description:
Masking is Double blind for RBV: two or more parties are unaware of the intervention assignment.

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

Criteria

Inclusion Criteria:

• Subjects chronically infected with HCV genotype 1
• Subjects with compensated cirrhosis
• HCV RNA ≥ 10,000 IU/mL at screening
• Treatment-naïve subjects with no previous exposure to an interferon formulation (ie, IFNα, pegIFNα), RBV, or HCV Direct Acting Antivirals (DAA) (protease, polymerase inhibitor, etc.)
• Treatment-experienced subjects are eligible including exposure to anti-HCV agents of a mechanistic class other than those contained in the DCV/ASV/BMS-791325 triple regimen is permitted. Examples of permitted agents include, but are not limited to nucleoside/nucleotide inhibitors of nonstructural protein 5B (NS5B) polymerase, inhibitors of cyclophilin, or inhibitors of microRNA.

Exclusion Criteria:

• Subjects without cirrhosis
• Liver or any other organ transplant
• Current or known history of cancer within 5 years prior to screening
• Documented or suspected hepatocellular carcinoma(HCC)
• Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01973049

Sponsors and Collaborators
Bristol-Myers Squibb

Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

More Information

No publications provided

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT01973049     History of Changes
Other Study ID Numbers:	AI443-113, 2013-002458-66
Study First Received:	October 25, 2013
Last Updated:	October 30, 2013
Health Authority:	United States: Food and Drug Administration Australia: Department of Health and Ageing Therapeutic Goods Administration Australia: National Health and Medical Research Council Canada: Health Canada France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) United States: Institutional Review Board

Additional relevant MeSH terms:

Hepatitis Hepatitis A Hepatitis, Chronic Hepatitis C Fibrosis Hepatitis C, Chronic Liver Cirrhosis Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections

Picornaviridae Infections RNA Virus Infections Flaviviridae Infections Pathologic Processes Ribavirin Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Antimetabolites Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 30, 2013

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