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

Hepatitis C Virus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01628692
• Other study ID #: AI444-062
• Secondary ID: 2012-000070-28
• Status: Completed
• Phase: Phase 2
• First received: June 25, 2012
• Last updated: October 29, 2015
• Start date: July 2012
• Est. completion date: November 2013

Study information

• Verified date: October 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardRussia: Ethics CommitteeRussia: Ministry of Health of the Russian FederationRussia: FSI Scientific Center of Expertise of Medical ApplicationHungary: National Institute of PharmacyChile: Instituto de Salud Pública de ChileGermany: Federal Institute for Drugs and Medical DevicesGermany: Ministry of HealthFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Spain: Spanish Agency of MedicinesArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: November 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Daclatasvir
Tablets, oral, 30 mg, once daily
• Simeprevir
Capsule, oral, 150 mg, once daily
• Ribavirin
Tablets, oral, 500-600 mg, twice daily

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
France	Local Institution	Creteil Cedex
France	Local Institution	Limoges
France	Local Institution	Marseille Cedex 08
France	Local Institution	Paris Cedex 13
France	Local Institution	Paris Cedex 14
France	Local Institution	Pessac
France	Local Institution	Vandoeuvre Les Nancy
Germany	Local Institution	Berlin
Germany	Local Institution	Frankfurt
Germany	Local Institution	Hamburg
Germany	Local Institution	Koeln
Hungary	Local Institution	Budapest
Hungary	Local Institution	Budapest
Hungary	Local Institution	Gyula
Spain	Local Institution	Barcelona
Spain	Local Institution	Madrid
Spain	Local Institution	Valencia
United States	Texas Clinical Research Institute, Llc	Arlington	Texas
United States	Metropolitan Research	Fairfax	Virginia
United States	Indiana University	Indianapolis	Indiana
United States	Johns Hopkins University	Lutherville	Maryland
United States	Nashville Medical Research Institute	Nashville	Tennessee
United States	Kaiser Permanente Med Ctr	San Francisco	California
United States	San Francisco General Hospital	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  France,  Germany,  Hungary,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response Rate at Post-treatment Week 12 (SVR12)	SVR12 rate was defined as hepatitis C virus (HCV) RNA levels to be	Post Treatment Week 12 (Follow-up period)	No
Secondary	Percentage of Participants With Rapid Virologic Response (RVR) at Week 4	RVR was defined as hepatitis C virus (HCV) RNA levels to be	Week 4	No
Secondary	Percentage of Participants With Complete Early Virologic Response (cEVR)	cEVR was defined as hepatitis C virus (HCV) RNA levels to be	Week 12	No
Secondary	Percentage of Participants With Extended Rapid Virologic Response (eRVR)	eRVR were defined as hepatitis C virus (HCV) RNA levels to be	Week 4 and Week 12	No
Secondary	Percentage of Participants With End of Treatment Response (EOTR)	EOTR were defined as hepatitis C virus (HCV) RNA levels	End of treatment (Week 24)	No
Secondary	Percentage of Participants With Sustained Virologic Response at Week 12 (SVR12) by rs12979860 Single Nucleotide Polymorphisms in the IL-28B Gene Categories	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.	Baseline, post-treatment Week 12 (Follow-up period)	No
Secondary	Number of Participants With Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) and Who Died	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.	From start of treatment (Day 1) up to 7 days post last dose of study treatment (Week 24)	Yes

External Links

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