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

Hepatitis C Virus Clinical Trial

— Hallmark QUAD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01573351
• Other study ID #: AI447-029
• Secondary ID: 2011-005422-21
• Status: Completed
• Phase: Phase 3
• First received: April 5, 2012
• Last updated: September 23, 2015
• Start date: May 2012
• Est. completion date: December 2013

Study information

• Verified date: September 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationKorea: Food and Drug AdministrationTaiwan: Department of HealthTaiwan: National Bureau of Controlled DrugsAustralia: Department of Health and Ageing Therapeutic Goods AdministrationAustralia: National Health and Medical Research CouncilBrazil: Ministry of HealthCanada: Health CanadaRussia: Ethics CommitteeRussia: Ministry of Health of the Russian FederationRussia: FSI Scientific Center of Expertise of Medical ApplicationGermany: Federal Institute for Drugs and Medical DevicesSwitzerland: SwissmedicFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Spain: Spanish Agency of MedicinesArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaMexico: Federal Commission for Sanitary Risks ProtectionNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: The Danish National Committee on Biomedical Research EthicsSweden: Medical Products AgencySweden: The National Board of Health and WelfareSweden: Swedish Data Inspection BoardSweden: Swedish National Council on Medical EthicsItaly: Ministry of HealthItaly: National Bioethics CommitteeItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthItaly: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Description:

• ASV = Asunaprevir (BMS-650032)

• DCV = Daclatasvir (BMS-790052)

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

• Rib = Ribavirin (RBV)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 398
• Est. completion date: December 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C
• Hepatitis C Virus

Intervention

Drug:
• Asunaprevir

• Daclatasvir

• Peg-interferon Alfa-2a

• Ribavirin

Locations

Country	Name	City	State
Argentina	Local Institution	Ciudad De Buenos Aires	Buenos Aires
Argentina	Local Institution	Mar Del Plata	Buenos Aires
Argentina	Local Institution	Prov. Buenos Aires	Buenos Aires
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution	Vancouver	British Columbia
Canada	Local Institution	Victoria	British Columbia
Denmark	Local Institution	Aalborg
Denmark	Local Institution	Hvidovre
Denmark	Local Institution	Odense
France	Local Institution	Creteil
France	Local Institution	Montpellier Cedex 5
France	Local Institution	Nice Cedex 03
France	Local Institution	Paris Cedex 12
France	Local Institution	Paris Cedex 14
France	Local Institution	Pessac
Germany	Local Institution	Berlin
Germany	Local Institution	Duesseldorf
Germany	Local Institution	Frankfurt
Germany	Local Institution	Freiburg
Germany	Local Institution	Hamburg
Germany	Local Institution	Heidelberg
Germany	Local Institution	Tuebingen
Italy	Local Institution	Brescia
Italy	Local Institution	Cisanello (pisa)
Italy	Local Institution	Milano
Italy	Local Institution	Palermo
Korea, Republic of	Local Institution	Bucheon-si
Korea, Republic of	Local Institution	Busan
Korea, Republic of	Local Institution	Busan
Korea, Republic of	Local Institution	Busan
Korea, Republic of	Local Institution	Daegu
Korea, Republic of	Local Institution	Gyeongsangnam-do
Korea, Republic of	Local Institution	Incheon
Korea, Republic of	Local Institution	Incheon
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Mexico	Local Institution	Mexico	Distrito Federal
Mexico	Local Institution	Mexico City	Estado De Mexico
Netherlands	Local Institution	Amsterdam
Netherlands	Local Institution	Rotterdam
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Saint-Petersburg
Russian Federation	Local Institution	Stavropol
Russian Federation	Local Institution	Tyumen
Spain	Local Institution	Alcorcon
Spain	Local Institution	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Sevilla
Sweden	Local Institution	Gvteborg
Sweden	Local Institution	Stockholm
Switzerland	Local Institution	Bern
Switzerland	Local Institution	Lausanne
Taiwan	Local Institution	Chia-Yi
Taiwan	Local Institution	Kaohsiung
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Taipei
United States	University Of Colorado Denver And Hospital	Aurora	Colorado
United States	University Of North Carolina At Chapel Hill School Of Med	Chapel Hill	North Carolina
United States	University Of Chicago Medical Center	Chicago	Illinois
United States	University Of Cincinnati	Cincinnati	Ohio
United States	South Denver Gastroenterology, Pc	Englewood	Colorado
United States	Gastro One	Germantown	Tennessee
United States	Baylor College Of Medicine	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	Scripps Clinic	La Jolla	California
United States	Scpmg/ Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Dean Clinic	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	University Of Miami Schiff Center For Liver Diseases	Miami	Florida
United States	Alabama Liver & Digestive Specialists (Alds)	Montgomery	Alabama
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University Of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Mcguire Dvamc	Richmond	Virginia
United States	Texas Liver Institute	San Antonio	Texas
United States	Options Health Research, Llc	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Denmark,  France,  Germany,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Russian Federation,  Spain,  Sweden,  Switzerland,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	Proportion of patients with SVR12 (HCV RNA < LOQ at post-treatment Week 12) for HCV genotype 4 subjects		Post-treatment Week 12	No

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form