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

Phase 2

Completed

Conditions: Hepatitis C Virus

Interventions: Drug: Daclatasvir
Drug: Simeprevir
Drug: Ribavirin

Registration Number: NCT01628692

Lead Sponsor: Bristol-Myers Squibb

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 230

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 2: (Genotype 1b) Daclatasvir + Simeprevir + Ribavirin	Daclatasvir	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.
Cohort 1: (Genotype 1b) Daclatasvir + Simeprevir	Daclatasvir	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
Cohort 1: (Genotype 1b) Daclatasvir + Simeprevir	Simeprevir	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
Cohort 4: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin	Daclatasvir	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.
Cohort 2: (Genotype 1b) Daclatasvir + Simeprevir + Ribavirin	Simeprevir	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.
Cohort 3: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin	Daclatasvir	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.
Cohort 3: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin	Simeprevir	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.
Cohort 3: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin	Ribavirin	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.
Cohort 4: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin	Simeprevir	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.
Cohort 4: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin	Ribavirin	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response Rate at Post-treatment Week 12 (SVR12)	Post Treatment Week 12 (Follow-up period)	SVR12 rate was defined as hepatitis C virus (HCV) RNA levels to be \<lower limit of quantitation, target detected or target not detected, at post-treatment Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Rapid Virologic Response (RVR) at Week 4	Week 4	RVR was defined as hepatitis C virus (HCV) RNA levels to be \<lower limit of quantitation, target not detected at Week 4. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Percentage of Participants With Extended Rapid Virologic Response (eRVR)	Week 4 and Week 12	eRVR were defined as hepatitis C virus (HCV) RNA levels to be \<lower limit of quantitation, target not detected at both Week 4 and Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Percentage of Participants With End of Treatment Response (EOTR)	End of treatment (Week 24)	EOTR were defined as hepatitis C virus (HCV) RNA levels \<lower limit of quantitation, target not detected at end of treatment. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died	From start of treatment (Day 1) up to 7 days post last dose of study treatment (Week 24)	AE was defined as any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. SAE was defined as a medical event that at any dose resulted in death, persistent or significant disability/incapacity, or drug dependency/abuse; was life-threatening, an important medical event, or a congenital anomaly/birth defect; or required or prolonged hospitalization. Based on the severity, AEs were categorized as Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
Percentage of Participants With Complete Early Virologic Response (cEVR)	Week 12	cEVR was defined as hepatitis C virus (HCV) RNA levels to be \<lower limit of quantitation, target not detected at Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.
Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) by rs12979860 Single Nucleotide Polymorphisms in the IL-28B Gene Categories	Baseline, post-treatment Week 12 (Follow-up period)	Participants were categorized into 3 genotypes based on single nucleotide polymorphisms in the IL28B gene. SVR12 was defined as hepatitis C virus (HCV) RNA levels below lower limit of quantitation, target detected or target not detected at follow-up Week 12. HCV RNA levels were measured by the Roche COBAS® TaqMan® HCV Test version 2.0 from the central laboratory.

Trial Locations

Locations (8): San Francisco General Hospital
🇺🇸
San Francisco, California, United States
Kaiser Permanente Med Ctr
🇺🇸
San Francisco, California, United States
Indiana University
🇺🇸
Indianapolis, Indiana, United States
Johns Hopkins University
🇺🇸
Lutherville, Maryland, United States
Nashville Medical Research Institute
🇺🇸
Nashville, Tennessee, United States
Texas Clinical Research Institute, Llc
🇺🇸
Arlington, Texas, United States
Metropolitan Research
🇺🇸
Fairfax, Virginia, United States
Local Institution
🇪🇸
Valencia, Spain
San Francisco General Hospital
🇺🇸San Francisco, California, United States