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A Study to Assess the Efficacy and Safety of the Combination of Simeprevir and Daclatasvir in Chronic Hepatitis C Genotype 1b-Infected Participants (COMMIT)

Primary Purpose

Hepatitis C, Chronic

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Simeprevir
Daclatasvir
Sponsored by
Janssen-Cilag International NV
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C, Chronic focused on measuring Hepatitis C Chronic, Simeprevir, Daclatasvir

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Participant must have chronic Hepatitis C virus (HCV) genotype 1b infection confirmed at Screening
  • Participant must have HCV ribonucleic acid (RNA) greater than (>) 10,000 international unit per milliliter (IU/mL) at Screening
  • Participant must have documented fibrosis stage at Screening (or between Screening and Day 1 [baseline]). Liver disease will be staged based on one of the following methods. a) Shear wave elastography (Fibroscan) within less than or equal to (<=) 6 months before Screening or between Screening and Day 1 (baseline). METAVIR F3 > 9.6 Kilopascals (kPa) and the cut-off for cirrhosis is greater than or equal to (>=) 14.6 kPa. b) A biopsy documenting METAVIR F3-F4. Biopsy performed within the 24 months before Screening will be accepted for participants with METAVIR score F3. For cirrhotic participants (METAVIR score F4) a biopsy performed at any previous time is acceptable
  • Participants who have cirrhosis must have an hepatic imaging procedure (ultrasound, computed tomography [CT] scan or magnetic resonance imaging [MRI]) within 6 months prior to the Screening visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma
  • Participant must have a body mass index (BMI) >= 18 Kilogram per meter^2 (kg/m^2)
  • Participant must be treatment naive (that is, have not received prior treatment for HCV with any approved or investigational drug)

Exclusion Criteria:

  • Participant has co-infection with HCV of another genotype; a) Participant who has HCV genotype 1b has coinfection with HCV of a genotype other than genotype 1b
  • Chronic HCV genotype 1b-infected participant who has the presence of genetic variants coding for the NS5A-Y93H and/or L31M/V amino acid substitutions at Screening
  • Participant has evidence of current or previous episodes of hepatic decompensation (including controlled or uncontrolled ascites, bleeding varices or hepatic encephalopathy)
  • Participant has chronic liver disease of a non-HCV etiology (including but not limited to hemochromatosis, Wilson's disease, alfa 1-antitrypsin deficiency, cholangitis, drug- or alcohol-related liver disease, primary biliary cirrhosis)
  • Participant has any other uncontrolled clinically significant disease or clinically significant findings during Screening that in the opinion of the investigator could compromise the participants' safety or could interfere with the participant participating in and completing the study
  • Participant has coinfection with hepatitis A or hepatitis B virus (hepatitis A antibody immunoglobulin M [IgM] or hepatitis B surface antigen [HBsAg] positive at Screening)
  • Participant has received a solid organ transplant

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Simeprevir + Daclatasvir

Arm Description

Participants who have Hepatitis C virus (HCV) genotype 1b infection with advanced fibrosis or compensated cirrhosis (METAVIR F3/F4) will receive simeprevir 150 milligram (mg) capsule and daclatasvir 60 mg tablet orally once daily for 12 or 24 weeks.

Outcomes

Primary Outcome Measures

Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)
Participants were considered to have reached SVR12, if 12 weeks after the actual end of treatment (EOT), hepatitis C virus (HCV) ribonucleic acid (RNA) was less than lower limit of quantification (<LLOQ) (detectable or undetectable).

Secondary Outcome Measures

Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Study Drug Treatment (SVR4)
Participants were considered to have reached SVR4, if 4 weeks after the actual EOT, HCV RNA was <LLOQ (detectable or undetectable).
Percentage of Participants With SVR 24 Weeks After End of Study Drug Treatment (SVR 24)
Participants were considered to have reached SVR24, if 24 weeks after the actual EOT, HCV RNA was <LLOQ (detectable or undetectable).
Percentage of Participants With On-treatment Failure
Participants were considered on-treatment failures if they did not achieve SVR12 and had (confirmed) detectable HCV RNA, ie, <LLOQ detectable or greater than equal to (>=) LLOQ at EOT.
Number of Participants With Viral Breakthrough
Participants were considered to have had viral breakthrough if they had a confirmed greater than (>) 1.0 log10 international units/milliliter (IU/mL) increase in HCV RNA from nadir OR confirmed HCV RNA >100 IU/mL while previously having achieved HCV RNA <LLOQ when on study treatment.
Number of Participants With Viral Relapse
Participants were considered to have had viral relapse if they did not achieve SVR12 and met the following conditions: had HCV RNA <LLOQ (undetectable) at EOT and had HCV RNA >=LLOQ during the follow-up period.

Full Information

First Posted
October 15, 2014
Last Updated
February 7, 2017
Sponsor
Janssen-Cilag International NV
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1. Study Identification

Unique Protocol Identification Number
NCT02268864
Brief Title
A Study to Assess the Efficacy and Safety of the Combination of Simeprevir and Daclatasvir in Chronic Hepatitis C Genotype 1b-Infected Participants
Acronym
COMMIT
Official Title
A Phase 2, Open-label Study to Investigate the Efficacy and Safety of the Combination of Simeprevir and Daclatasvir in Chronic Hepatitis C Genotype 1b-Infected Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
January 2015 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen-Cilag International NV

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine the efficacy of a 12- or 24-week treatment regimen of simeprevir in combination with daclatasvir, as measured by sustain virologic response 12 (SVR12), in treatment-naive, chronic hepatitis C virus (HCV) genotype 1b-infected participants who have advanced fibrosis or compensated cirrhosis (METAVIR F3/F4).
Detailed Description
This is an open-label (all people know which treatment the participants receive) study to investigate the efficacy, safety and tolerability of simeprevir and daclatasvir in chronic Hepatitis (inflammation of the liver) C virus (HCV) genotype 1b infected participants who are treatment-naive. The total study duration for each participant will be approximately 40 weeks or approximately 52 weeks. The study will consist of 4 parts: Screening Phase (approximately 4 weeks) and open-label treatment Phase (12 weeks), optional open label treatment phase extension (12 Weeks) and follow-up Phase (up to Week 40 or Week 52). Participants will receive simeprevir (150 milligram [mg] capsule) and daclatasvir (60 mg tablet) orally once daily for 12 or 24 weeks. Efficacy will be primarily evaluated by percentage of participants with SVR12. Participants' safety will be monitored throughout the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Chronic
Keywords
Hepatitis C Chronic, Simeprevir, Daclatasvir

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
106 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Simeprevir + Daclatasvir
Arm Type
Experimental
Arm Description
Participants who have Hepatitis C virus (HCV) genotype 1b infection with advanced fibrosis or compensated cirrhosis (METAVIR F3/F4) will receive simeprevir 150 milligram (mg) capsule and daclatasvir 60 mg tablet orally once daily for 12 or 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Simeprevir
Intervention Description
Simeprevir 150 mg oral capsule will be administered once daily for 12 or 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Daclatasvir
Intervention Description
Daclatasvir 60 mg oral tablet will be administered once daily for 12 or 24 weeks.
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)
Description
Participants were considered to have reached SVR12, if 12 weeks after the actual end of treatment (EOT), hepatitis C virus (HCV) ribonucleic acid (RNA) was less than lower limit of quantification (<LLOQ) (detectable or undetectable).
Time Frame
At 12 weeks after end of treatment
Secondary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Study Drug Treatment (SVR4)
Description
Participants were considered to have reached SVR4, if 4 weeks after the actual EOT, HCV RNA was <LLOQ (detectable or undetectable).
Time Frame
At 4 weeks after actual EOT
Title
Percentage of Participants With SVR 24 Weeks After End of Study Drug Treatment (SVR 24)
Description
Participants were considered to have reached SVR24, if 24 weeks after the actual EOT, HCV RNA was <LLOQ (detectable or undetectable).
Time Frame
At 24 weeks after actual EOT
Title
Percentage of Participants With On-treatment Failure
Description
Participants were considered on-treatment failures if they did not achieve SVR12 and had (confirmed) detectable HCV RNA, ie, <LLOQ detectable or greater than equal to (>=) LLOQ at EOT.
Time Frame
Up to Week 24 after actual EOT
Title
Number of Participants With Viral Breakthrough
Description
Participants were considered to have had viral breakthrough if they had a confirmed greater than (>) 1.0 log10 international units/milliliter (IU/mL) increase in HCV RNA from nadir OR confirmed HCV RNA >100 IU/mL while previously having achieved HCV RNA <LLOQ when on study treatment.
Time Frame
Up to Week 24
Title
Number of Participants With Viral Relapse
Description
Participants were considered to have had viral relapse if they did not achieve SVR12 and met the following conditions: had HCV RNA <LLOQ (undetectable) at EOT and had HCV RNA >=LLOQ during the follow-up period.
Time Frame
Up to Week 24 after actual EOT

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participant must have chronic Hepatitis C virus (HCV) genotype 1b infection confirmed at Screening Participant must have HCV ribonucleic acid (RNA) greater than (>) 10,000 international unit per milliliter (IU/mL) at Screening Participant must have documented fibrosis stage at Screening (or between Screening and Day 1 [baseline]). Liver disease will be staged based on one of the following methods. a) Shear wave elastography (Fibroscan) within less than or equal to (<=) 6 months before Screening or between Screening and Day 1 (baseline). METAVIR F3 > 9.6 Kilopascals (kPa) and the cut-off for cirrhosis is greater than or equal to (>=) 14.6 kPa. b) A biopsy documenting METAVIR F3-F4. Biopsy performed within the 24 months before Screening will be accepted for participants with METAVIR score F3. For cirrhotic participants (METAVIR score F4) a biopsy performed at any previous time is acceptable Participants who have cirrhosis must have an hepatic imaging procedure (ultrasound, computed tomography [CT] scan or magnetic resonance imaging [MRI]) within 6 months prior to the Screening visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma Participant must have a body mass index (BMI) >= 18 Kilogram per meter^2 (kg/m^2) Participant must be treatment naive (that is, have not received prior treatment for HCV with any approved or investigational drug) Exclusion Criteria: Participant has co-infection with HCV of another genotype; a) Participant who has HCV genotype 1b has coinfection with HCV of a genotype other than genotype 1b Chronic HCV genotype 1b-infected participant who has the presence of genetic variants coding for the NS5A-Y93H and/or L31M/V amino acid substitutions at Screening Participant has evidence of current or previous episodes of hepatic decompensation (including controlled or uncontrolled ascites, bleeding varices or hepatic encephalopathy) Participant has chronic liver disease of a non-HCV etiology (including but not limited to hemochromatosis, Wilson's disease, alfa 1-antitrypsin deficiency, cholangitis, drug- or alcohol-related liver disease, primary biliary cirrhosis) Participant has any other uncontrolled clinically significant disease or clinically significant findings during Screening that in the opinion of the investigator could compromise the participants' safety or could interfere with the participant participating in and completing the study Participant has coinfection with hepatitis A or hepatitis B virus (hepatitis A antibody immunoglobulin M [IgM] or hepatitis B surface antigen [HBsAg] positive at Screening) Participant has received a solid organ transplant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen-Cilag International NV Clinical Trial
Organizational Affiliation
Janssen-Cilag International NV
Official's Role
Study Director
Facility Information:
City
Antwerpen
Country
Belgium
City
Brussel
Country
Belgium
City
Gent
Country
Belgium
City
Creteil
Country
France
City
Lyon
Country
France
City
Montpellier
Country
France
City
Nice N/A
Country
France
City
Paris Cedex 12
Country
France
City
Paris
Country
France
City
Vandoeuvre Les Nancy
Country
France
City
Frankfurt
Country
Germany
City
Hamburg
Country
Germany
City
Hannover
Country
Germany
City
Kiel
Country
Germany
City
Tübingen
Country
Germany
City
Würzburg
Country
Germany
City
Budapest
Country
Hungary
City
Debrecen
Country
Hungary
City
Badalona
Country
Spain
City
Barcelona
Country
Spain
City
Santander
Country
Spain
City
Valencia
Country
Spain
City
Birmingham
Country
United Kingdom
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
28135777
Citation
Hezode C, Almasio PL, Bourgeois S, Buggisch P, Brown A, Diago M, Horsmans Y, Serfaty L, Szalay F, Gaeta GB, Planas R, Schlag M, Lonjon-Domanec I, Omoruyi E, DeMasi R, Zeuzem S. Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naive patients with hepatitis C virus genotype 1b and advanced liver disease. Liver Int. 2017 Sep;37(9):1304-1313. doi: 10.1111/liv.13376. Epub 2017 Mar 13.
Results Reference
derived

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A Study to Assess the Efficacy and Safety of the Combination of Simeprevir and Daclatasvir in Chronic Hepatitis C Genotype 1b-Infected Participants

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