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

Primary Purpose

Hepatitis C Virus

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Asunaprevir
Daclatasvir
Peg-interferon Alfa-2a
Ribavirin
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C Virus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Alabama Liver & Digestive Specialists (Alds)
  • Scripps Clinic
  • Scpmg/ Kaiser Permanente Los Angeles Medical Center
  • University Of Colorado Denver And Hospital
  • South Denver Gastroenterology, Pc
  • Mayo Clinic
  • University Of Miami Schiff Center For Liver Diseases
  • University Of Chicago Medical Center
  • North Shore University Hospital
  • University Of North Carolina At Chapel Hill School Of Med
  • University Of Cincinnati
  • Options Health Research, Llc
  • Oregon Health & Science University
  • University Of Pennsylvania
  • Thomas Jefferson University
  • Gastro One
  • Baylor College Of Medicine
  • Texas Liver Institute
  • Mcguire Dvamc
  • Dean Clinic
  • Local Institution
  • Local Institution
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Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm Description

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

Outcomes

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

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
Proportion of subjects with SVR12 (HCV RNA < LOQ at post-treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28 gene
Proportion of subjects with HCV RNA undetectable
Proportion of subjects with HCV RNA < LOQ
Proportion of patients with SVR12 (HCV RNA < LOQ at post-treatment Week 12) for HCV genotype 4 subjects

Full Information

First Posted
April 5, 2012
Last Updated
September 23, 2015
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT01573351
Brief Title
Phase III Hallmark QUAD: ASV+DCV+Peg+Rib (Nulls/Partials)
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
September 2013 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
No

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Virus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
398 (Actual)

8. Arms, Groups, and Interventions

Arm Title
QUAD: Asunaprevir+Daclatasvir+Peg-interferon Alfa-2a+Ribavirin
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Asunaprevir
Other Intervention Name(s)
BMS-650032
Intervention Type
Drug
Intervention Name(s)
Daclatasvir
Other Intervention Name(s)
BMS-790052
Intervention Type
Drug
Intervention Name(s)
Peg-interferon Alfa-2a
Other Intervention Name(s)
Pegasys®
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Other Intervention Name(s)
Copegus®
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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)
Title
Proportion of patients with SVR12 (HCV RNA < LOQ at post-treatment Week 12) for HCV genotype 4 subjects
Time Frame
Post-treatment Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Alabama Liver & Digestive Specialists (Alds)
City
Montgomery
State/Province
Alabama
ZIP/Postal Code
36116
Country
United States
Facility Name
Scripps Clinic
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Scpmg/ Kaiser Permanente Los Angeles Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
University Of Colorado Denver And Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
South Denver Gastroenterology, Pc
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
University Of Miami Schiff Center For Liver Diseases
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University Of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1432
Country
United States
Facility Name
North Shore University Hospital
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
University Of North Carolina At Chapel Hill School Of Med
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7584
Country
United States
Facility Name
University Of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Options Health Research, Llc
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74104
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University Of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Gastro One
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Baylor College Of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Liver Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Mcguire Dvamc
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
Facility Name
Dean Clinic
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53715
Country
United States
Facility Name
Local Institution
City
Ciudad De Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
C1121ABE
Country
Argentina
Facility Name
Local Institution
City
Mar Del Plata
State/Province
Buenos Aires
ZIP/Postal Code
7600
Country
Argentina
Facility Name
Local Institution
City
Prov. Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
1629
Country
Argentina
Facility Name
Local Institution
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
Local Institution
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 2K5
Country
Canada
Facility Name
Local Institution
City
Victoria
State/Province
British Columbia
ZIP/Postal Code
V8V 3P9
Country
Canada
Facility Name
Local Institution
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6H 3M1
Country
Canada
Facility Name
Local Institution
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4P9
Country
Canada
Facility Name
Local Institution
City
Aalborg
ZIP/Postal Code
9100
Country
Denmark
Facility Name
Local Institution
City
Hvidovre
ZIP/Postal Code
2650
Country
Denmark
Facility Name
Local Institution
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Local Institution
City
Creteil
ZIP/Postal Code
94000
Country
France
Facility Name
Local Institution
City
Montpellier Cedex 5
ZIP/Postal Code
34295
Country
France
Facility Name
Local Institution
City
Nice Cedex 03
ZIP/Postal Code
06202
Country
France
Facility Name
Local Institution
City
Paris Cedex 12
ZIP/Postal Code
75571
Country
France
Facility Name
Local Institution
City
Paris Cedex 14
ZIP/Postal Code
75679
Country
France
Facility Name
Local Institution
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Local Institution
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Local Institution
City
Duesseldorf
ZIP/Postal Code
40237
Country
Germany
Facility Name
Local Institution
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Local Institution
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Local Institution
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Local Institution
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Local Institution
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Local Institution
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Local Institution
City
Cisanello (pisa)
ZIP/Postal Code
56124
Country
Italy
Facility Name
Local Institution
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Local Institution
City
Palermo
ZIP/Postal Code
90127
Country
Italy
Facility Name
Local Institution
City
Bucheon-si
ZIP/Postal Code
420-767
Country
Korea, Republic of
Facility Name
Local Institution
City
Busan
ZIP/Postal Code
602-715
Country
Korea, Republic of
Facility Name
Local Institution
City
Busan
ZIP/Postal Code
602-739
Country
Korea, Republic of
Facility Name
Local Institution
City
Busan
ZIP/Postal Code
614-735
Country
Korea, Republic of
Facility Name
Local Institution
City
Daegu
ZIP/Postal Code
700-721
Country
Korea, Republic of
Facility Name
Local Institution
City
Gyeongsangnam-do
ZIP/Postal Code
626-770
Country
Korea, Republic of
Facility Name
Local Institution
City
Incheon
ZIP/Postal Code
400-711
Country
Korea, Republic of
Facility Name
Local Institution
City
Incheon
ZIP/Postal Code
403-720
Country
Korea, Republic of
Facility Name
Local Institution
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Local Institution
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Local Institution
City
Mexico
State/Province
Distrito Federal
ZIP/Postal Code
03720
Country
Mexico
Facility Name
Local Institution
City
Mexico City
State/Province
Estado De Mexico
ZIP/Postal Code
06700
Country
Mexico
Facility Name
Local Institution
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Local Institution
City
Rotterdam
ZIP/Postal Code
3015 CE
Country
Netherlands
Facility Name
Local Institution
City
Moscow
ZIP/Postal Code
117593
Country
Russian Federation
Facility Name
Local Institution
City
Moscow
ZIP/Postal Code
127015
Country
Russian Federation
Facility Name
Local Institution
City
Saint-Petersburg
ZIP/Postal Code
194044
Country
Russian Federation
Facility Name
Local Institution
City
Stavropol
ZIP/Postal Code
355000
Country
Russian Federation
Facility Name
Local Institution
City
Tyumen
ZIP/Postal Code
625026
Country
Russian Federation
Facility Name
Local Institution
City
Alcorcon
ZIP/Postal Code
28922
Country
Spain
Facility Name
Local Institution
City
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Local Institution
City
Madrid
ZIP/Postal Code
28029
Country
Spain
Facility Name
Local Institution
City
Sevilla
ZIP/Postal Code
41014
Country
Spain
Facility Name
Local Institution
City
Gvteborg
ZIP/Postal Code
SE-41685
Country
Sweden
Facility Name
Local Institution
City
Stockholm
ZIP/Postal Code
141 86
Country
Sweden
Facility Name
Local Institution
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Local Institution
City
Lausanne
ZIP/Postal Code
1011
Country
Switzerland
Facility Name
Local Institution
City
Chia-Yi
ZIP/Postal Code
600
Country
Taiwan
Facility Name
Local Institution
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
Facility Name
Local Institution
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Facility Name
Local Institution
City
Taipei
ZIP/Postal Code
11217
Country
Taiwan

12. IPD Sharing Statement

Citations:
PubMed Identifier
25703086
Citation
Jensen D, Sherman KE, Hezode 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.
Results Reference
derived
Links:
URL
http://www.bms.com/studyconnect/Pages/home.aspx
Description
BMS clinical trial educational resource

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

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