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An Efficacy and Safety Study of a 8 or 12-Week Treatment Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naive and Experienced Participants With Chronic Genotype 4 Hepatitis C Virus Infection

Primary Purpose

Hepatitis C

Status

Completed

Phase

Phase 2

Locations

Egypt

Study Type

Interventional

Intervention

Simeprevir

Sofosbuvir

About this trial

This is an interventional treatment trial for Hepatitis C focused on measuring Hepatitis C, Simeprevir, Sofosbuvir, Healthy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Participant must have hepatitis C virus (HCV) genotype 4 infection (confirmed at screening)
Participant must have HCV ribonucleic acid (RNA) greater than (>) 10,000 international unit per milliliter (IU/mL) at screening
In participants with cirrhosis, a documented hepatic imaging procedure (ultrasound, computed tomography [CT] scan, or magnetic resonance imaging [MRI]) within 6 months before baseline (Day 1) to exclude hepatocellular carcinoma is required
A woman of childbearing potential must have a negative serum (beta human chorionic gonadotropin at screening and a negative urine pregnancy test on Day 1 before first dose of study drug
Females of childbearing potential or males with a female partner of childbearing potential must agree to use 2 highly effective contraceptive methods (one of which is a barrier method; eg, condom or diaphragm) from Day 1 (baseline) and continue until 30 days after the end of treatment (EOT) (or longer if dictated by local regulations), or not be heterosexually active, or be a vasectomized male subject or a female subject with a vasectomized partner, or be a female (subject or partner of male subject) of non-childbearing potential (ie, postmenopausal for at least 2 years or surgically sterile)

Exclusion Criteria:

Participant has evidence of clinical hepatic decompensation (history or current evidence of ascites, bleeding varices, or hepatic encephalopathy)
Participant has any liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A, drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HCV liver disease considered clinically significant by the investigator
Participant is infected/co-infected with non-genotype 4 HCV
Participant has any other active clinically significant disease or clinically significant findings during screening of medical history, physical examination, laboratory testing or electrocardiogram (ECG) recordings that, in the investigator's opinion, would compromise the participant's safety or could interfere with the participant participating in and completing the study
Participant has history of malignancy within 5 years of the screening visit (exceptions: skin carcinomas, carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator is considered cured with minimal risk of recurrence)

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Group A1

Group A2

Group B

Arm Description

Participants without cirrhosis will receive simeprevir 150 milligram (mg) capsule along with sofosbuvir 400 mg tablet, orally, once daily for 8 weeks.

Participants without cirrhosis will receive simeprevir 150 mg capsule along with sofosbuvir 400 mg tablet, orally, once daily for 12 weeks.

Participants with cirrhosis will receive simeprevir 150 mg capsule along with sofosbuvir 400 mg tablet, orally, once daily for 12 weeks.

Outcomes

Primary Outcome Measures

Percentage of Participants With Sustained Virologic Response at Week 12 After End of Treatment (SVR12)

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

Secondary Outcome Measures

Percentage of Participants With Sustained Virologic Response at Week 4 After End of Treatment (SVR4)

SVR4 is defined as HCV RNA <LLOQ;15 IU/mL, at 4 weeks after EOT.

Percentage of Participants With Sustained Virologic Response at Week 24 After End of Treatment (SVR24)

SVR24 is defined as HCV RNA <LLOQ;15 IU/mL, at 24 weeks after EOT.

Percentage of Participants With on-treatment Failure

Participants will be considered on-treatment failures if they have (confirmed) detectable HCV RNA, that is <LLOQ;15 IU/mL, detectable or greater than or equal to (>=) LLOQ at EOT.

Percentage of Participants With Viral Relapse

Participants will be considered to have viral relapse if they do not achieve SVR at Week 4, 12 and 24 after EOT and meet the following conditions 1) HCV RNA <LLOQ;15 IU/mL, undetectable at EOT, 2) HCV RNA >=LLOQ;15 IU/mL during the follow-up period.

Percentage of Participants With On-treatment Response

On-treatment virologic response is defined as the change from baseline in log10 hepatitis C virus ribonucleic acid.

Percentage of Participants With Viral Breakthrough

Viral breakthrough is defined as 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; 15 IU/mL.

Full Information

NCT ID

NCT02278419

First Posted

October 28, 2014

Last Updated

October 13, 2016

Sponsor

Janssen-Cilag International NV

1. Study Identification

Unique Protocol Identification Number

NCT02278419

Brief Title

An Efficacy and Safety Study of a 8 or 12-Week Treatment Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naive and Experienced Participants With Chronic Genotype 4 Hepatitis C Virus Infection

Official Title

A Phase 2a, Partly Randomized, Open-label Trial to Investigate the Efficacy and Safety of an 8 or 12-Week Treatment Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naive and Experienced Subjects With Chronic Genotype 4 Hepatitis C Infection

Study Type

Interventional

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Completed

Study Start Date

December 2014 (undefined)

Primary Completion Date

October 2015 (Actual)

Study Completion Date

October 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen-Cilag International NV

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of simeprevir in combination with sofosbuvir for 8 or 12 weeks versus a historical control, with respect to the percentage of participants with sustained virologic response at 12 weeks after end of treatment (SVR12) in the overall population.

Detailed Description

This is a partly randomized, open-label (identity of study drug will be known to volunteer and study staff), multicenter (when more than one hospital or medical school team work on a medical research study) study. The study will consist of a screening period of up to 4 weeks, an open-label treatment period of 8 weeks or 12 weeks, and a post-treatment follow-up period until 24 weeks after end of treatment (EOT). Participants without cirrhosis will be assigned to Group A wherein half of the participants will receive 8 week treatment in Group A1 and remaining participants will receive 12 week treatment in Group A2. Participants with cirrhosis, will be assigned to Group B to receive simeprevir in combination with sofosbuvir for 12 weeks. The duration of participation for each participant, including the screening period, will be approximately 36 or 40 weeks for 8 or 12 week treatment, respectively. Efficacy will be primarily assessed by percentage of participants with SVR12. Participants' safety will be evaluated throughout the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatitis C

Keywords

Hepatitis C, Simeprevir, Sofosbuvir, Healthy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

63 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group A1

Arm Type

Experimental

Arm Description

Participants without cirrhosis will receive simeprevir 150 milligram (mg) capsule along with sofosbuvir 400 mg tablet, orally, once daily for 8 weeks.

Arm Title

Group A2

Arm Type

Experimental

Arm Description

Participants without cirrhosis will receive simeprevir 150 mg capsule along with sofosbuvir 400 mg tablet, orally, once daily for 12 weeks.

Arm Title

Group B

Arm Type

Experimental

Arm Description

Participants with cirrhosis will receive simeprevir 150 mg capsule along with sofosbuvir 400 mg tablet, orally, once daily for 12 weeks.

Intervention Type

Drug

Intervention Name(s)

Simeprevir

Intervention Description

Simeprevir 150 mg capsule orally, once daily for 8 weeks in Group A1, 12 weeks in Group A2 and Group B.

Intervention Type

Drug

Intervention Name(s)

Sofosbuvir

Intervention Description

Sofosbuvir 400 mg tablet orally, once daily for 8 weeks in Group A1, 12 weeks in Group A2 and Group B.

Primary Outcome Measure Information:

Title

Percentage of Participants With Sustained Virologic Response at Week 12 After End of Treatment (SVR12)

Description

Time Frame

12 weeks after end of treatment (EOT) (EOT; Week 8 for Group A1, Week 12 for Group A2 and Group B)

Secondary Outcome Measure Information:

Title

Percentage of Participants With Sustained Virologic Response at Week 4 After End of Treatment (SVR4)

Description

SVR4 is defined as HCV RNA <LLOQ;15 IU/mL, at 4 weeks after EOT.

Time Frame

4 weeks after EOT (EOT; Week 8 for Group A1, Week 12 for Group A2 and Group B)

Title

Percentage of Participants With Sustained Virologic Response at Week 24 After End of Treatment (SVR24)

Description

SVR24 is defined as HCV RNA <LLOQ;15 IU/mL, at 24 weeks after EOT.

Time Frame

24 weeks after EOT (EOT; Week 8 for Group A1, Week 12 for Group A2 and Group B)

Title

Percentage of Participants With on-treatment Failure

Description

Participants will be considered on-treatment failures if they have (confirmed) detectable HCV RNA, that is <LLOQ;15 IU/mL, detectable or greater than or equal to (>=) LLOQ at EOT.

Time Frame

EOT (EOT; Week 8 for Group A1, Week 12 for Group A2 and Group B)

Title

Percentage of Participants With Viral Relapse

Description

Time Frame

EOT (Week 8 for Group A1, Week 12 for Group A2 and Group B), Weeks 4, 12 and 24 after end of treatment

Title

Percentage of Participants With On-treatment Response

Description

On-treatment virologic response is defined as the change from baseline in log10 hepatitis C virus ribonucleic acid.

Time Frame

Week 1, 2, 4, 8 and EOT for all groups, Week 12 for Group A2 and Group B

Title

Percentage of Participants With Viral Breakthrough

Description

Viral breakthrough is defined as 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; 15 IU/mL.

Time Frame

Week 1 up to Week 8 in Group A1, Week 1 up to Week 12 in Group A2 and Group B

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participant must have hepatitis C virus (HCV) genotype 4 infection (confirmed at screening) Participant must have HCV ribonucleic acid (RNA) greater than (>) 10,000 international unit per milliliter (IU/mL) at screening In participants with cirrhosis, a documented hepatic imaging procedure (ultrasound, computed tomography [CT] scan, or magnetic resonance imaging [MRI]) within 6 months before baseline (Day 1) to exclude hepatocellular carcinoma is required A woman of childbearing potential must have a negative serum (beta human chorionic gonadotropin at screening and a negative urine pregnancy test on Day 1 before first dose of study drug Females of childbearing potential or males with a female partner of childbearing potential must agree to use 2 highly effective contraceptive methods (one of which is a barrier method; eg, condom or diaphragm) from Day 1 (baseline) and continue until 30 days after the end of treatment (EOT) (or longer if dictated by local regulations), or not be heterosexually active, or be a vasectomized male subject or a female subject with a vasectomized partner, or be a female (subject or partner of male subject) of non-childbearing potential (ie, postmenopausal for at least 2 years or surgically sterile) Exclusion Criteria: Participant has evidence of clinical hepatic decompensation (history or current evidence of ascites, bleeding varices, or hepatic encephalopathy) Participant has any liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A, drug- or alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic steatohepatitis, primary biliary cirrhosis, or any other non-HCV liver disease considered clinically significant by the investigator Participant is infected/co-infected with non-genotype 4 HCV Participant has any other active clinically significant disease or clinically significant findings during screening of medical history, physical examination, laboratory testing or electrocardiogram (ECG) recordings that, in the investigator's opinion, would compromise the participant's safety or could interfere with the participant participating in and completing the study Participant has history of malignancy within 5 years of the screening visit (exceptions: skin carcinomas, carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator is considered cured with minimal risk of recurrence)

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

Cairo

Country

Egypt

City

Menoufiya

Country

Egypt

12. IPD Sharing Statement

Citations:

PubMed Identifier

27790789

Citation

El Raziky M, Gamil M, Ashour MK, Sameea EA, Doss W, Hamada Y, Van Dooren G, DeMasi R, Keim S, Lonjon-Domanec I, Hammad R, Hashim MS, Hassany M, Waked I. Simeprevir plus sofosbuvir for eight or 12 weeks in treatment-naive and treatment-experienced hepatitis C virus genotype 4 patients with or without cirrhosis. J Viral Hepat. 2017 Feb;24(2):102-110. doi: 10.1111/jvh.12625. Epub 2016 Oct 27.

Results Reference

derived

Links:

URL

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_7051&studyid=7813&filename=CR104970_CSR.pdf

Description

A Phase2a,Partly Randomized,Open-label Trial to Investigate the Efficacy and Safety of an 8 or 12 Week Treatment Regimen of Simeprevir in CombinationWith Sofosbuvir in Treatment-Naïve and Experienced Subjects With Chronic Genotype 4 HepatitisC Infection

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