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

NCT01628692 | Completed Phase 2 Results DMC

• 2 other identifiers: AI444-0622012-000070-28
• Study Type: interventional
• Target: 230
• Locations: 6 countries
• Sites: 26

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.

Conditions

Hepatitis C Virus

Outcome Measures

Primary Outcomes (1)

• 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 \<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.

  Post Treatment Week 12 (Follow-up period)

Secondary Outcomes (6)

• Percentage of Participants With Rapid Virologic Response (RVR) at Week 4

  Week 4

• Percentage of Participants With Complete Early Virologic Response (cEVR)

  Week 12

• Percentage of Participants With Extended Rapid Virologic Response (eRVR)

  Week 4 and Week 12

• Percentage of Participants With End of Treatment Response (EOTR)

  End of treatment (Week 24)

• 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)

Study Arms (4)

Cohort 1: (Genotype 1b) Daclatasvir + Simeprevir

EXPERIMENTAL

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

Drug: Daclatasvir; Drug: Simeprevir

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

EXPERIMENTAL

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.

Drug: Daclatasvir; Drug: Simeprevir

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

EXPERIMENTAL

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.

Drug: Daclatasvir; Drug: Simeprevir; Drug: Ribavirin

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

EXPERIMENTAL

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.

Drug: Daclatasvir; Drug: Simeprevir; Drug: Ribavirin

Interventions

Daclatasvir DRUG

Tablets, oral, 30 mg, once daily

Also known as: BMS-790052

Cohort 1: (Genotype 1b) Daclatasvir + Simeprevir; Cohort 2: (Genotype 1b) Daclatasvir + Simeprevir + Ribavirin; Cohort 3: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin; Cohort 4: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin

Simeprevir DRUG

Capsule, oral, 150 mg, once daily

Also known as: TMC435

Cohort 1: (Genotype 1b) Daclatasvir + Simeprevir; Cohort 2: (Genotype 1b) Daclatasvir + Simeprevir + Ribavirin; Cohort 3: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin; Cohort 4: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin

Ribavirin DRUG

Tablets, oral, 500-600 mg, twice daily

Cohort 3: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin; Cohort 4: (Genotype 1a) Daclatasvir + Simeprevir + Ribavirin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (26)

San Francisco General Hospital

San Francisco, California, 94110, United States

Location

Kaiser Permanente Med Ctr

San Francisco, California, 94118, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins University

Lutherville, Maryland, 21093, United States

Location

Nashville Medical Research Institute

Nashville, Tennessee, 37205, United States

Location

Texas Clinical Research Institute, Llc

Arlington, Texas, 76012, United States

Location

Metropolitan Research

Fairfax, Virginia, 22031, United States

Location

Local Institution

Buenos Aires, Buenos Aires, 1119, Argentina

Location

Local Institution

Buenos Aires, Buenos Aires, C1181ACH, Argentina

Location

Local Institution

Créteil, 94010, France

Location

Local Institution

Limoges, 87042, France

Location

Local Institution

Marseille, 13285, France

Location

Local Institution

Paris, 75651, France

Location

Local Institution

Paris, 75679, France

Location

Local Institution

Pessac, 33600, France

Location

Local Institution

Vandœuvre-lès-Nancy, 54511, France

Location

Local Institution

Berlin, 10969, Germany

Location

Local Institution

Cologne, 50937, Germany

Location

Local Institution

Frankfurt, 60590, Germany

Location

Local Institution

Hamburg, 20099, Germany

Location

Local Institution

Budapest, 1097, Hungary

Location

Local Institution

Budapest, 1126, Hungary

Location

Local Institution

Gyula, 5700, Hungary

Location

Local Institution

Barcelona, 08035, Spain

Location

Local Institution

Madrid, 28046, Spain

Location

Local Institution

Valencia, 46010, Spain

Location

Related Publications (1)

• 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.

  PMID: 26453968 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Hepatitis C

Interventions

daclatasvir; Simeprevir; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2012
• First Posted: June 27, 2012
• Study Start: July 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: November 1, 2013
• Last Updated: February 23, 2017
• Results First Posted: November 30, 2015

Record last verified: 2017-01

Locations

FR (7); AR (2); US (7); HU (3); ES (3); DE (4)