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

• Sponsor: Janssen-Cilag International NV (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02268864
• Collaborator: (none)
• Enrollment: 106
• Locations: 24
• Arm: 1
• Duration (Months): 15
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.3

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: Simeprevir; Drug: Daclatasvir	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 106 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jan 1, 2015
• Actual Primary Completion Date: Jan 1, 2016
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Simeprevir + Daclatasvir 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.	Drug: Simeprevir; Simeprevir 150 mg oral capsule will be administered once daily for 12 or 24 weeks.; Drug: Daclatasvir; Daclatasvir 60 mg oral tablet will be administered once daily for 12 or 24 weeks.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

2. 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).

3. 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.

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Antwerpen		Belgium
2		Brussel		Belgium
3		Gent		Belgium
4		Creteil		France
5		Lyon		France
6		Montpellier		France
7		Nice N/A		France
8		Paris Cedex 12		France
9		Paris		France
10		Vandoeuvre Les Nancy		France
11		Frankfurt		Germany
12		Hamburg		Germany
13		Hannover		Germany
14		Kiel		Germany
15		Tübingen		Germany
16		Würzburg		Germany
17		Budapest		Hungary
18		Debrecen		Hungary
19		Badalona		Spain
20		Barcelona		Spain
21		Santander		Spain
22		Valencia		Spain
23		Birmingham		United Kingdom
24		London		United Kingdom

Sponsors and Collaborators

• Janssen-Cilag International NV

Investigators

• Study Director: Janssen-Cilag International NV Clinical Trial, Janssen-Cilag International NV

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen-Cilag International NV
• ClinicalTrials.gov Identifier: NCT02268864
• Other Study ID Numbers: CR105490; 2014-003413-28; TMC435HPC2019
• First Posted: Oct 20, 2014
• Last Update Posted: Mar 16, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Janssen-Cilag International NV: Hepatitis C Chronic; Simeprevir; Daclatasvir
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Simeprevir

Study Results

Participant Flow

Arm/Group Title	12 Weeks Prior Amendment	12 Weeks Post Amendment	24 Weeks Extension
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	17	25	64
COMPLETED	15	24	64
NOT COMPLETED	2	1	0

Baseline Characteristics

Arm/Group Title	12 Weeks Prior Amendment	12 Weeks Post Amendment	24 Weeks Extension	Total
Arm/Group Description	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.	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.	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.	Total of all reporting groups
Overall Participants	17	25	64	106
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	53.0 (15.34)	64.0 (14.77)	59.0 (12.6)	59.0 (13.53)
Sex: Female, Male (Count of Participants)
Female	5 29.4%	11 44%	27 42.2%	43 40.6%
Male	12 70.6%	14 56%	37 57.8%	63 59.4%
Region of Enrollment (Count of Participants)
Belgium	6 35.3%	1 4%	5 7.8%	12 11.3%
France	3 17.6%	3 12%	19 29.7%	25 23.6%
Germany	3 17.6%	3 12%	14 21.9%	20 18.9%
Hungary	4 23.5%	0 0%	8 12.5%	12 11.3%
Italy	0 0%	10 40%	6 9.4%	16 15.1%
Spain	1 5.9%	8 32%	11 17.2%	20 18.9%
United Kingdom	0 0%	0 0%	1 1.6%	1 0.9%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	12 Weeks Prior Amendment	12 Weeks Post Amendment	24 Weeks Extension
Arm/Group Description	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.	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.	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.
Measure Participants	17	25	64
Number (95% Confidence Interval) [percentage of participants]	70.6 415.3%	100 400%	93.8 146.6%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The ITT analysis set is defined as all participants who received at least one dose of simeprevir or daclatasvir.

Arm/Group Title	12 Weeks Prior Amendment	12 Weeks Post Amendment	24 Weeks Extension
Arm/Group Description	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.	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.	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.
Measure Participants	17	25	64
Number (95% Confidence Interval) [percentage of participants]	70.6 415.3%	100 400%	93.8 146.6%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The ITT analysis set is defined as all participants who received at least one dose of simeprevir or daclatasvir.

Arm/Group Title	12 Weeks Prior Amendment	12 Weeks Post Amendment	24 Weeks Extension
Arm/Group Description	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.	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.	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.
Measure Participants	17	25	64
Number (95% Confidence Interval) [percentage of participants]	70.6 415.3%	100 400%	93.8 146.6%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The ITT analysis set is defined as all participants who received at least one dose of simeprevir or daclatasvir.

Arm/Group Title	12 Weeks Prior Amendment	12 Weeks Post Amendment	24 Weeks Extension
Arm/Group Description	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.	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.	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.
Measure Participants	17	25	64
Number [percentage of participants]	29.4 172.9%	0.0 0%	4.7 7.3%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The ITT analysis set is defined as all participants who received at least one dose of simeprevir or daclatasvir.

Arm/Group Title	12 Weeks Prior Amendment	12 Weeks Post Amendment	24 Weeks Extension
Arm/Group Description	Simeprevir 150 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.	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.	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.
Measure Participants	17	25	64
Number [participants]	4 23.5%	0 0%	3 4.7%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The ITT analysis set is defined as all participants who received at least one dose of simeprevir or daclatasvir.

Arm/Group Title	12 Weeks Prior Amendment	12 Weeks Post Amendment	24 Weeks Extension
Arm/Group Description	Simeprevir 150 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.	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.	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.
Measure Participants	17	25	64
Number [participants]	0 0%	0 0%	1 1.6%

Adverse Events

Time Frame	Up to 24 weeks
Adverse Event Reporting Description	Total number of participants at risk reported in the 12-24 weeks were the same participants who continued the 24-weeks extension period after completion of 1-12 weeks treatment phase (up to Day 88).
Arm/Group Title	1-12 Weeks		12-24 Weeks
Arm/Group Description	Simeprevir 150 mg once daily as an oral capsule in combination with Daclatasvir 60 mg once daily as an oral tablet for participants who has adverse events (AEs) that started before or on day 88 on treatment.		Simeprevir 150 mg once daily as an oral capsule in combination with Daclatasvir 60 mg once daily as an oral tablet for participants who has AEs that started after day 88 on treatment.
All Cause Mortality
	1-12 Weeks		12-24 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	1-12 Weeks		12-24 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/106 (3.8%)		3/64 (4.7%)
Cardiac disorders
Atrial Fibrillation	1/106 (0.9%)		0/64 (0%)
Pericarditis	0/106 (0%)		1/64 (1.6%)
Gastrointestinal disorders
Abdominal Pain	1/106 (0.9%)		0/64 (0%)
Vomiting	1/106 (0.9%)		0/64 (0%)
Hepatobiliary disorders
Cholelithiasis	0/106 (0%)		1/64 (1.6%)
Injury, poisoning and procedural complications
Fall	0/106 (0%)		1/64 (1.6%)
Wound Haemorrhage	0/106 (0%)		1/64 (1.6%)
Renal and urinary disorders
Acute Kidney Injury	1/106 (0.9%)		0/64 (0%)
Skin and subcutaneous tissue disorders
Photosensitivity Reaction	1/106 (0.9%)		0/64 (0%)
Other (Not Including Serious) Adverse Events
	1-12 Weeks		12-24 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/106 (41.5%)		2/64 (3.1%)
General disorders
Asthenia	14/106 (13.2%)		1/64 (1.6%)
Fatigue	16/106 (15.1%)		1/64 (1.6%)
Nervous system disorders
Headache	16/106 (15.1%)		0/64 (0%)
Skin and subcutaneous tissue disorders
Pruritus	11/106 (10.4%)		0/64 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.