Clinical trial NCT01573351: Phase III Hallmark QUAD: ASV+DCV+Peg+Rib (Nulls/Partials)
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C Virus
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2012-04-09
Enrollment: 398
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)

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

Primary outcomes:
measure: 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
timeFrame: At 12 weeks post-treatment
Secondary outcomes:
measure: On-treatment safety, as measured by frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) through the end of treatment
timeFrame: Through the end of treatment (maximum up to 24 weeks) plus 7 days
measure: Proportion of subjects with SVR12 (HCV RNA < LOQ at post-treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28 gene
timeFrame: At post-treatment Week 12
measure: Proportion of subjects with HCV RNA undetectable
timeFrame: 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
measure: Proportion of subjects with HCV RNA < LOQ
timeFrame: 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)
measure: Proportion of patients with SVR12 (HCV RNA < LOQ at post-treatment Week 12) for HCV genotype 4 subjects
timeFrame: Post-treatment Week 12
Other outcomes:
Locations:
city: Montgomery
country: United States
facility: Alabama Liver & Digestive Specialists (Alds)
state: Alabama
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: Scpmg/ Kaiser Permanente Los Angeles Medical Center
state: California
city: Aurora
country: United States
facility: University Of Colorado Denver And Hospital
state: Colorado
city: Englewood
country: United States
facility: South Denver Gastroenterology, Pc
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: University Of Miami Schiff Center For Liver Diseases
state: Florida
city: Chicago
country: United States
facility: University Of Chicago Medical Center
state: Illinois
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: Chapel Hill
country: United States
facility: University Of North Carolina At Chapel Hill School Of Med
state: North Carolina
city: Cincinnati
country: United States
facility: University Of Cincinnati
state: Ohio
city: Tulsa
country: United States
facility: Options Health Research, Llc
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University Of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Houston
country: United States
facility: Baylor College Of Medicine
state: Texas
city: San Antonio
country: United States
facility: Texas Liver Institute
state: Texas
city: Richmond
country: United States
facility: Mcguire Dvamc
state: Virginia
city: Madison
country: United States
facility: Dean Clinic
state: Wisconsin
city: Ciudad De Buenos Aires
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Mar Del Plata
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Prov. Buenos Aires
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Vancouver
country: Canada
facility: Local Institution
state: British Columbia
city: Victoria
country: Canada
facility: Local Institution
state: British Columbia
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Aalborg
country: Denmark
facility: Local Institution
city: Hvidovre
country: Denmark
facility: Local Institution
city: Odense
country: Denmark
facility: Local Institution
city: Creteil
country: France
facility: Local Institution
city: Montpellier Cedex 5
country: France
facility: Local Institution
city: Nice Cedex 03
country: France
facility: Local Institution
city: Paris Cedex 12
country: France
facility: Local Institution
city: Paris Cedex 14
country: France
facility: Local Institution
city: Pessac
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Duesseldorf
country: Germany
facility: Local Institution
city: Frankfurt
country: Germany
facility: Local Institution
city: Freiburg
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Heidelberg
country: Germany
facility: Local Institution
city: Tuebingen
country: Germany
facility: Local Institution
city: Brescia
country: Italy
facility: Local Institution
city: Cisanello (pisa)
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Palermo
country: Italy
facility: Local Institution
city: Bucheon-si
country: Korea, Republic of
facility: Local Institution
city: Busan
country: Korea, Republic of
facility: Local Institution
city: Busan
country: Korea, Republic of
facility: Local Institution
city: Busan
country: Korea, Republic of
facility: Local Institution
city: Daegu
country: Korea, Republic of
facility: Local Institution
city: Gyeongsangnam-do
country: Korea, Republic of
facility: Local Institution
city: Incheon
country: Korea, Republic of
facility: Local Institution
city: Incheon
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Mexico
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Local Institution
state: Estado De Mexico
city: Amsterdam
country: Netherlands
facility: Local Institution
city: Rotterdam
country: Netherlands
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Saint-Petersburg
country: Russian Federation
facility: Local Institution
city: Stavropol
country: Russian Federation
facility: Local Institution
city: Tyumen
country: Russian Federation
facility: Local Institution
city: Alcorcon
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Sevilla
country: Spain
facility: Local Institution
city: Gvteborg
country: Sweden
facility: Local Institution
city: Stockholm
country: Sweden
facility: Local Institution
city: Bern
country: Switzerland
facility: Local Institution
city: Lausanne
country: Switzerland
facility: Local Institution
city: Chia-Yi
country: Taiwan
facility: Local Institution
city: Kaohsiung
country: Taiwan
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
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.