Clinical trial NCT02278419: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C
Keywords: Hepatitis C
Simeprevir
Sofosbuvir
Healthy
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2014-10-30
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response at Week 12 After End of Treatment (SVR12)
timeFrame: 12 weeks after end of treatment (EOT) (EOT; Week 8 for Group A1, Week 12 for Group A2 and Group B)
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response at Week 4 After End of Treatment (SVR4)
timeFrame: 4 weeks after EOT (EOT; Week 8 for Group A1, Week 12 for Group A2 and Group B)
measure: Percentage of Participants With Sustained Virologic Response at Week 24 After End of Treatment (SVR24)
timeFrame: 24 weeks after EOT (EOT; Week 8 for Group A1, Week 12 for Group A2 and Group B)
measure: Percentage of Participants With on-treatment Failure
timeFrame: EOT (EOT; Week 8 for Group A1, Week 12 for Group A2 and Group B)
measure: Percentage of Participants With Viral Relapse
timeFrame: EOT (Week 8 for Group A1, Week 12 for Group A2 and Group B), Weeks 4, 12 and 24 after end of treatment
measure: Percentage of Participants With On-treatment Response
timeFrame: Week 1, 2, 4, 8 and EOT for all groups, Week 12 for Group A2 and Group B
measure: Percentage of Participants With Viral Breakthrough
timeFrame: Week 1 up to Week 8 in Group A1, Week 1 up to Week 12 in Group A2 and Group B
Other outcomes:
Locations:
city: Cairo
country: Egypt
city: Menoufiya
country: Egypt
Study officials:
affiliation: Janssen-Cilag International NV
name: Janssen-Cilag International NV Clinical Trial
role: STUDY_DIRECTOR
References:
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.