Study of Daclatasvir (BMS-790052) and Simeprevir (TMC435) in Patients With Genotype 1 Chronic Hepatitis C Virus

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 2

Conditions: Hepatitis C Virus

Treatments: Drug: Ribavirin; Drug: Simeprevir; Drug: Daclatasvir

Study type: Interventional

Funder types: Industry

Identifiers

NCT01628692

AI444-062

2012-000070-28 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 230 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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230 participants in 4 patient groups

Cohort 1: (Genotype 1b) Daclatasvir + Simeprevir

Experimental group

Description:

Participants with hepatitis C virus genotype 1b received daclatasvir, 30 mg, once daily with or without food + simeprevir, 150 mg, once daily with a meal for 12 weeks

Treatment:

Drug: Simeprevir

Drug: Daclatasvir

Cohort 2: (Genotype 1b) Daclatasvir + Simeprevir + Ribavirin

Experimental group

Description:

Participants with hepatitis C virus genotype 1b received daclatasvir, 30 mg, once daily with or without food + simeprivir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing \<75 kg received a total ribavirin dose of 1000 mg per day; those weighing \>=75 kg received 1200 mg per day) for 12 weeks.

Treatment:

Drug: Simeprevir

Drug: Daclatasvir

Cohort 3: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin

Experimental group

Description:

Participants with hepatitis C virus genotype 1a received daclatasvir, 30 mg, once daily with or without food + simeprevir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing \<75 kg received a total ribavirin dose of 1000 mg per day; those weighing \>=75 kg received 1200 mg per day) for 12 weeks.

Treatment:

Drug: Ribavirin

Drug: Simeprevir

Drug: Daclatasvir

Cohort 4: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin

Experimental group

Description:

Participants with hepatitis C virus genotype 1a received daclatasvir, 30 mg, once daily with or without food + simeprivir, 150 mg, once daily with a meal + ribavirin, twice daily with food (patients weighing \<75 kg received a total ribavirin dose of 1000 mg per day; those weighing \>=75 kg received 1200 mg per day.

Treatment:

Drug: Ribavirin

Drug: Simeprevir

Drug: Daclatasvir