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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02268864

Acronym

COMMIT

Enrollment

106

Registered

2014-10-20

Start date

2015-01-31

Completion date

2016-04-30

Last updated

2017-03-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatitis C, Chronic

Keywords

Hepatitis C Chronic, Simeprevir, Daclatasvir

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.

Interventions

DRUGSimeprevir

Simeprevir 150 mg oral capsule will be administered once daily for 12 or 24 weeks.

DRUGDaclatasvir

Daclatasvir 60 mg oral tablet will be administered once daily for 12 or 24 weeks.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

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

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)	At 12 weeks after end of treatment	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

Measure	Time frame	Description
Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Study Drug Treatment (SVR4)	At 4 weeks after actual EOT	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)	At 24 weeks after actual EOT	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	Up to Week 24 after actual EOT	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	Up to Week 24	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	Up to Week 24 after actual EOT	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.

Countries

Belgium, France, Germany, Hungary, Spain, United Kingdom

Participant flow

Participants by arm

Arm	Count
12 Weeks Prior Amendment Simeprevir 150 milligram (mg) once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who completed the 12-week treatment before Amendment 3 of the protocol was implemented.	17
12 Weeks Post Amendment Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for a 12-week treatment period after amendment.	25
24 Weeks Extension Simeprevir 150 mg once daily as an oral capsule in combination with daclatasvir 60 mg once daily as an oral tablet for participants who opted for an extended 24-week treatment after amendment.	64
Total	106

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Death	0	1	0
Overall Study	Withdrawal by Subject	2	0	0

Baseline characteristics

Characteristic	12 Weeks Prior Amendment	12 Weeks Post Amendment	24 Weeks Extension	Total
Age, Continuous	53.0 years FULL_RANGE 15.34	64.0 years FULL_RANGE 14.77	59.0 years FULL_RANGE 12.6	59.0 years FULL_RANGE 13.53
Region of Enrollment Belgium	6 Participants	1 Participants	5 Participants	12 Participants
Region of Enrollment France	3 Participants	3 Participants	19 Participants	25 Participants
Region of Enrollment Germany	3 Participants	3 Participants	14 Participants	20 Participants
Region of Enrollment Hungary	4 Participants	0 Participants	8 Participants	12 Participants
Region of Enrollment Italy	0 Participants	10 Participants	6 Participants	16 Participants
Region of Enrollment Spain	1 Participants	8 Participants	11 Participants	20 Participants
Region of Enrollment United Kingdom	0 Participants	0 Participants	1 Participants	1 Participants
Sex: Female, Male Female	5 Participants	11 Participants	27 Participants	43 Participants
Sex: Female, Male Male	12 Participants	14 Participants	37 Participants	63 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	44 / 106	2 / 64
serious Total, serious adverse events	4 / 106	3 / 64

Outcome results

Primary

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).

Time frame: At 12 weeks after end of treatment

Population: The intent-to-treat (ITT) analysis set is defined as all participants who received at least one dose of simeprevir or daclatasvir.

Arm	Measure	Value (NUMBER)
12 Weeks Prior Amendment	Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)	70.6 percentage of participants
12 Weeks Post Amendment	Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)	100 percentage of participants
24 Weeks Extension	Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)	93.8 percentage of participants

Secondary

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.

Time frame: Up to Week 24