Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Subjects With Chronic Genotype 4 Hepatitis C Virus Infection

• Sponsor: Janssen R&D Ireland (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02250807
• Collaborator: (none)
• Enrollment: 40
• Locations: 7
• Arm: 1
• Duration (Months): 11
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to show superiority of simeprevir (SMV) in combination with sofosbuvir for 12 weeks versus a historical control. Historical control will be a composite of the observed historical sustained virological response at Week 12 (SVR12) rates of SMV in combination with (pegylated) interferon (PegIFN)/ribavirin (RBV) of the subpopulations in study HPC3011 (NCT01567735) and will depend on the percentage of treatment-naive, prior relapser, prior non-responder, interferon (IFN)-intolerant and other subjects enrolled in this study.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C; Genotype 4 Chronic Hepatitis C	Drug: Simeprevir; Drug: Sofosbuvir	Phase 3

Detailed Description

This is a Phase 3, open-label (all people know the identity of the intervention), single-arm, multicenter study (conducted at multiple sites). The study consists of 3 periods: a Screening period (up to 4 weeks), Treatment period (12 Weeks) and Post treatment follow-up period (until 24 weeks after end of treatment). The duration of the subjects' participation will be approximately 40 weeks. In the treatment period subjects will receive oral capsule simeprevir along with oral tablet sofosbuvir once daily for 12 weeks. Primarily efficacy will be evaluated as percentage of subjects with sustained virologic response at Week 12 after the end of treatment. Subjects' safety will be monitored throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Open-Label, Single-Arm Study to Investigate the Efficacy and Safety of a 12-Week Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naive or -Experienced Subjects With Chronic Genotype 4 Hepatitis C Virus Infection
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Simeprevir and Sofosbuvir Subjects will receive oral capsule of Simeprevir 150 milligram (mg) along with oral tablet of sofosbuvir 400 mg, once a day from Day 1 up to Week 12.	Drug: Simeprevir; Subjects will receive oral capsule of Simeprevir 150 mg, once a day from Day 1 up to Week 12.; Other Names: TMC435 ; Drug: Sofosbuvir; Subjects will receive oral tablet of sofosbuvir 400 mg, once a day from Day 1 up to Week 12.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12) [12 weeks after EOT]

   SVR12 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 12 weeks after actual EOT.

Secondary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Therapy (SVR4) [4 weeks after EOT]

   SVR4 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 4 weeks after actual EOT.

2. Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Therapy (SVR24) [At 24 weeks after EOT]

   Participants were considered to have reached SVR24, if at the time point of SVR24 (that is [i.e.], 24 weeks after the end of treatment [EOT]) the following condition has been met: HCV RNA < lower limit of quantification (LLOQ), i.e., 15 IU/mL, detectable or undetectable.

3. Percentage of Participants With On-treatment Virologic Response of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) [Week 2, 3, 4, 12 and EOT]

   Percentage of participants with HCV RNA less than (<) 15 IU/mL undetectable or detectable or detectable /undetectable at specific time points were observed.

4. Percentage of Participants With On-Treatment Failure [through 12 weeks (EOT)]

   Participants were considered on-treatment failures if they have at EOT (confirmed) detectable HCV RNA, i.e., <LLOQ detectable or >=LLOQ.

5. Percentage of Participants With Viral Breakthrough [Up to follow-up Week 24]

   Participants with confirmed >1.0 log10 increase in HCV RNA from nadir or confirmed HCV RNA >100 IU/mL in participants who had previously achieved HCV RNA <LLOQ.

6. Percentage of Participants With Viral Relapse [Up to follow-up week 24]

   Participants were considered to have viral relapse if they did not achieve SVR12 and meet the following conditions: 1) at EOT, HCV RNA less than (<)LLOQ, undetectable, and 2) during the follow-up period, HCV RNA greater than or equal to (>=)LLOQ.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects with confirmed hepatitis C virus (HCV) with HCV RNA greater than (>) 10000 international unit per milliliter (IU/mL)

• Subjects who are treatment naive or treatment-experienced.

• Subjects must have documentation of a liver biopsy or fibroscan or agree to have one during screening

• Subjects with cirrhosis must have an hepatic imaging procedure (ultrasound, CT scan or magnetic resonance imaging [MRI]) within 6 months before the screening visit (or during the screening period) with no findings suspicious for hepatocellular carcinoma (HCC)

• Women of childbearing potential or men with a female partner of childbearing potential must agree to use an effective form of contraception, or not be heterosexually active, or of nonchildbearing potential

Exclusion Criteria:

• Evidence of clinical hepatic decompensation

• Any liver disease of non-HCV etiology

• Subjects with a past history of treatment with an approved or investigational DAA

• Co-infection with human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening)

• Infection/co-infection with HCV non-genotype 4

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Badalona		Spain
2		Barcelona		Spain
3		Madrid		Spain
4		Santander N/A		Spain
5		Sevilla N/A		Spain
6		Sevilla		Spain
7		Valencia		Spain

Sponsors and Collaborators

• Janssen R&D Ireland

Investigators

• Study Director: Janssen R&D Ireland Clinical Trials, Janssen R&D Ireland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen R&D Ireland
• ClinicalTrials.gov Identifier: NCT02250807
• Other Study ID Numbers: CR105429; TMC435HPC3021; 2014-003446-27; NCT02256176
• First Posted: Sep 26, 2014
• Last Update Posted: Nov 17, 2016
• Last Verified: Sep 1, 2016

• Keywords provided by Janssen R&D Ireland: Chronic hepatitis C; Genotype 4 chronic hepatitis C; Simeprevir; Sofosbuvir
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Virus Diseases; Hepatitis; Hepatitis, Chronic; Sofosbuvir; Simeprevir

Study Results

Participant Flow

Arm/Group Title	SMV+SOF 12 Weeks
Arm/Group Description	Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.
Period Title: Overall Study
STARTED	40
COMPLETED	40
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	SMV+SOF 12 Weeks
Arm/Group Description	Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.
Overall Participants	40
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	51
Sex: Female, Male (Count of Participants)
Female	11 27.5%
Male	29 72.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)
Description	SVR12 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 12 weeks after actual EOT.
Time Frame	12 weeks after EOT

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).

Arm/Group Title	SMV+SOF 12 Weeks
Arm/Group Description	Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.
Measure Participants	40
Number (95% Confidence Interval) [percentage of participants]	100 250%

2. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Therapy (SVR4)
Description	SVR4 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 4 weeks after actual EOT.
Time Frame	4 weeks after EOT

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).

Arm/Group Title	SMV+SOF 12 Weeks
Arm/Group Description	Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.
Measure Participants	40
Number (95% Confidence Interval) [percentage of participants]	100 250%

3. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Therapy (SVR24)
Description	Participants were considered to have reached SVR24, if at the time point of SVR24 (that is [i.e.], 24 weeks after the end of treatment [EOT]) the following condition has been met: HCV RNA < lower limit of quantification (LLOQ), i.e., 15 IU/mL, detectable or undetectable.
Time Frame	At 24 weeks after EOT

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).

Arm/Group Title	SMV+SOF 12 Weeks
Arm/Group Description	Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.
Measure Participants	40
Number (95% Confidence Interval) [percentage of participants]	100 250%

4. Secondary Outcome

Title	Percentage of Participants With On-treatment Virologic Response of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Description	Percentage of participants with HCV RNA less than (<) 15 IU/mL undetectable or detectable or detectable /undetectable at specific time points were observed.
Time Frame	Week 2, 3, 4, 12 and EOT

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).

Arm/Group Title	SMV+SOF 12 Weeks
Arm/Group Description	Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.
Measure Participants	40
Week 2: < 100 IU/mL	87.5 218.8%
Week 2: < 15 IU/mL undetectable/detectable	40.0 100%
Week 2: < 15 IU/mL undetectable	17.5 43.8%
Week 3: < 100 IU/mL	100.0 250%
Week 3: < 15 IU/mL undetectable/detectable	82.5 206.3%
Week 3: < 15 IU/mL undetectable	40.0 100%
Week 4: < 100 IU/mL	100.0 250%
Week 4: < 15 IU/mL undetectable/detectable	87.5 218.8%
Week 4: < 15 IU/mL undetectable (RVR)	65.0 162.5%
Week 12: < 100 IU/mL	100.0 250%
Week 12: < 15 IU/mL undetectable/detectable	100.0 250%
Week 12: < 15 IU/mL undetectable	100.0 250%
End of Treatment (EOT): < 100 IU/mL	100.0 250%
EOT: < 15 IU/mL undetectable/detectable	100.0 250%
EOT: < 15 IU/mL undetectable	100.0 250%

5. Secondary Outcome

Title	Percentage of Participants With On-Treatment Failure
Description	Participants were considered on-treatment failures if they have at EOT (confirmed) detectable HCV RNA, i.e., <LLOQ detectable or >=LLOQ.
Time Frame	through 12 weeks (EOT)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).

Arm/Group Title	SMV+SOF 12 Weeks
Arm/Group Description	Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.
Measure Participants	40
Number [percentage of participants]	0 0%

6. Secondary Outcome

Title	Percentage of Participants With Viral Breakthrough
Description	Participants with confirmed >1.0 log10 increase in HCV RNA from nadir or confirmed HCV RNA >100 IU/mL in participants who had previously achieved HCV RNA <LLOQ.
Time Frame	Up to follow-up Week 24

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).

Arm/Group Title	SMV+SOF 12 Weeks
Arm/Group Description	Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.
Measure Participants	40
Number [percentage of participants]	0 0%

7. Secondary Outcome

Title	Percentage of Participants With Viral Relapse
Description	Participants were considered to have viral relapse if they did not achieve SVR12 and meet the following conditions: 1) at EOT, HCV RNA less than (<)LLOQ, undetectable, and 2) during the follow-up period, HCV RNA greater than or equal to (>=)LLOQ.
Time Frame	Up to follow-up week 24

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).

Arm/Group Title	SMV+SOF 12 Weeks
Arm/Group Description	Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.
Measure Participants	40
Number [percentage of participants]	0 0%

Adverse Events

Time Frame	Up to EOT (Week 12)
Arm/Group Title	SMV+SOF 12 Weeks
Arm/Group Description	Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.
All Cause Mortality
	SMV+SOF 12 Weeks
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	SMV+SOF 12 Weeks
	Affected / at Risk (%)	# Events
Total	0/40 (0%)
Other (Not Including Serious) Adverse Events
	SMV+SOF 12 Weeks
	Affected / at Risk (%)	# Events
Total	17/40 (42.5%)
Gastrointestinal disorders
Constipation	2/40 (5%)
General disorders
Asthenia	3/40 (7.5%)
Nervous system disorders
Headache	8/40 (20%)
Respiratory, thoracic and mediastinal disorders
Catarrh	3/40 (7.5%)
Skin and subcutaneous tissue disorders
Erythema	2/40 (5%)
Rash	2/40 (5%)

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.