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

Phase 3

Completed

• Conditions: Hepatitis C Virus
• Interventions: Drug: Asunaprevir; Drug: Daclatasvir; Drug: Peg-interferon Alfa-2a; Drug: Ribavirin

• Registration Number: NCT01573351
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

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.

Detailed Description

* ASV = Asunaprevir (BMS-650032)

* DCV = Daclatasvir (BMS-790052)

* Peg = Peg-interferon Alfa-2a (PegIFN)

* Rib = Ribavirin (RBV)

Study Timeline

• Study First Submitted: 2012-04-05
• Study First Submitted QC: 2012-04-06
• Study First Posted: 2012-04-09
• Study Start: 2012-05
• Primary Completion: 2013-09
• Study Completion: 2013-12
• Status Verified: 2015-09
• Disposition First Submitted: 2015-09-23
• Disposition First Submitted QC: 2015-09-23
• Last Update Submitted: 2015-09-23
• Disposition First Posted: 2015-10-09
• Last Update Posted: 2015-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 398

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
QUAD: Asunaprevir+Daclatasvir+Peg-interferon Alfa-2a+Ribavirin	Asunaprevir	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
QUAD: Asunaprevir+Daclatasvir+Peg-interferon Alfa-2a+Ribavirin	Daclatasvir	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
QUAD: Asunaprevir+Daclatasvir+Peg-interferon Alfa-2a+Ribavirin	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
QUAD: Asunaprevir+Daclatasvir+Peg-interferon Alfa-2a+Ribavirin	Peg-interferon Alfa-2a	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

Primary Outcome Measures

Name	Time	Method
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	At 12 weeks post-treatment

Secondary Outcome Measures

Name	Time	Method
On-treatment safety, as measured by frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) through the end of treatment	Through the end of treatment (maximum up to 24 weeks) plus 7 days
Proportion of subjects with HCV RNA undetectable	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
Proportion of subjects with SVR12 (HCV RNA < LOQ at post-treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28 gene	At post-treatment Week 12
Proportion of subjects with HCV RNA < LOQ	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)
Proportion of patients with SVR12 (HCV RNA < LOQ at post-treatment Week 12) for HCV genotype 4 subjects	Post-treatment Week 12

Trial Locations

Locations (21)

University Of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States

Gastro One; 🇺🇸 Germantown, Tennessee, United States

Local Institution; 🇨🇳 Taipei, Taiwan

University Of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

South Denver Gastroenterology, Pc; 🇺🇸 Englewood, Colorado, United States

North Shore University Hospital; 🇺🇸 Manhasset, New York, United States

University Of Miami Schiff Center For Liver Diseases; 🇺🇸 Miami, Florida, United States

Baylor College Of Medicine; 🇺🇸 Houston, Texas, United States

Mayo Clinic; 🇺🇸 Jacksonville, Florida, United States

Scpmg/ Kaiser Permanente Los Angeles Medical Center; 🇺🇸 Los Angeles, California, United States

Alabama Liver & Digestive Specialists (Alds); 🇺🇸 Montgomery, Alabama, United States

Scripps Clinic; 🇺🇸 La Jolla, California, United States

University Of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Options Health Research, Llc; 🇺🇸 Tulsa, Oklahoma, United States

University Of North Carolina At Chapel Hill School Of Med; 🇺🇸 Chapel Hill, North Carolina, United States

University Of Colorado Denver And Hospital; 🇺🇸 Aurora, Colorado, United States

Texas Liver Institute; 🇺🇸 San Antonio, Texas, United States

Mcguire Dvamc; 🇺🇸 Richmond, Virginia, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Dean Clinic; 🇺🇸 Madison, Wisconsin, United States

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States