Clinical trial NCT01628692: Study of Daclatasvir (BMS-790052) and Simeprevir (TMC435) in Patients With Genotype 1 Chronic Hepatitis C Virus
Official title: A Phase 2, Open-Label Study of Daclatasvir (BMS-790052) and TMC435 in Combination With or Without Ribavirin (RBV) For Treatment-Naive Subjects or Null Responders to Prior Peginterferon Alfa (PegIFN)/RBV Therapy With Genotype 1 Chronic Hepatitis C
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C Virus
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Janssen Research & Development, LLC
First posted: 2012-06-27
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and efficacy of daclatasvir and simeprevir with and without ribavirin for genotype 1 chronic hepatitis C virus infection in patients who are treatment-naive or null responders to previous pegylated interferon/ribavirin therapy.


Eligibility criteria: Key Inclusion Criteria:

* Hepatitis C virus (HCV) genotype 1a or 1b
* Males and females, ≥18 years of age
* HCV RNA ≥10,000 IU/mL
* Participants with compensated cirrhosis are permitted

  * Advanced fibrosis (F3/F4) is capped at approximately 35% of the total treated population with a minimum of 20% F4 patients
  * If no cirrhosis, a liver biopsy within 3 years prior to enrollment
  * If cirrhosis is present, any prior liver biopsy

Key Exclusion Criteria:

* Liver or any other transplant (other than cornea and hair)
* Evidence of a medical condition contributing to chronic liver disease other than HCV infection
* Current or known history of cancer, (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment
* Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
* Patients infected with HIV or hepatitis B virus
* Gastrointestinal disease impacting absorption of study drug
* Uncontrolled diabetes or hypertension
* Prior exposure to an HCV direct-acting agent
* Any criteria that would exclude the patient from receiving ribavirin
* Absolute neutrophil count \<1.5\*1,000,000,000 cells/L (\<1.2\*1,000,000,000 cells/L for Black/African Americans)
* Platelets \<90\*1,000,000,000 cells/L
* Hemoglobin \<12 g/dL for females, \<13 g/dL for males
* Alanine aminotransferase ≥5\*upper limit of normal
* In patients without cirrhosis, total bilirubin ≥2 mg/dL unless patient has a documented history of Gilbert's disease
* In patients with cirrhosis, total bilirubin o ≥1.5 mg/dL
* International normalized ratio ≥1.7
* QTcF or QTcB \>500 mSec
* Creatinine clearance ≤50 mL/min
* Alpha fetoprotein (AFP) \>100 ng/mL OR
* AFP ≥50 ng/mL and ≤100 ng/mL requiring liver ultrasound
* Albumin \<3.5 g/dL

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response Rate at Post-treatment Week 12 (SVR12)
timeFrame: Post Treatment Week 12 (Follow-up period)
Secondary outcomes:
measure: Percentage of Participants With Rapid Virologic Response (RVR) at Week 4
timeFrame: Week 4
measure: Percentage of Participants With Complete Early Virologic Response (cEVR)
timeFrame: Week 12
measure: Percentage of Participants With Extended Rapid Virologic Response (eRVR)
timeFrame: Week 4 and Week 12
measure: Percentage of Participants With End of Treatment Response (EOTR)
timeFrame: End of treatment (Week 24)
measure: Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) by rs12979860 Single Nucleotide Polymorphisms in the IL-28B Gene Categories
timeFrame: Baseline, post-treatment Week 12 (Follow-up period)
measure: Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died
timeFrame: From start of treatment (Day 1) up to 7 days post last dose of study treatment (Week 24)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco General Hospital
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Med Ctr
state: California
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Lutherville
country: United States
facility: Johns Hopkins University
state: Maryland
city: Nashville
country: United States
facility: Nashville Medical Research Institute
state: Tennessee
city: Arlington
country: United States
facility: Texas Clinical Research Institute, Llc
state: Texas
city: Fairfax
country: United States
facility: Metropolitan Research
state: Virginia
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Creteil Cedex
country: France
facility: Local Institution
city: Limoges
country: France
facility: Local Institution
city: Marseille Cedex 08
country: France
facility: Local Institution
city: Paris Cedex 13
country: France
facility: Local Institution
city: Paris Cedex 14
country: France
facility: Local Institution
city: Pessac
country: France
facility: Local Institution
city: Vandoeuvre Les Nancy
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Frankfurt
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Koeln
country: Germany
facility: Local Institution
city: Budapest
country: Hungary
facility: Local Institution
city: Budapest
country: Hungary
facility: Local Institution
city: Gyula
country: Hungary
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Valencia
country: Spain
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Zeuzem S, Hezode C, Bronowicki JP, Loustaud-Ratti V, Gea F, Buti M, Olveira A, Banyai T, Al-Assi MT, Petersen J, Thabut D, Gadano A, Pruitt R, Makara M, Bourliere M, Pol S, Beumont-Mauviel M, Ouwerkerk-Mahadevan S, Picchio G, Bifano M, McPhee F, Boparai N, Cheung K, Hughes EA, Noviello S; LEAGUE-1 Study Team. Daclatasvir plus simeprevir with or without ribavirin for the treatment of chronic hepatitis C virus genotype 1 infection. J Hepatol. 2016 Feb;64(2):292-300. doi: 10.1016/j.jhep.2015.09.024. Epub 2015 Oct 8.