A Study to Investigate the Safety, Pharmacokinetics, and Efficacy of Combination Treatment of AL-335, Odalasvir, and Simeprevir in Japanese Participants With Chronic Hepatitis C Genotype 1 or 2 Virus Infection, With or Without Compensated Cirrhosis Who Are Direct Acting Antiviral Treatment-naive

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and tolerability of a combination treatment of AL-335, odalasvir (ODV), and simeprevir (SMV) for 8 weeks in Japanese participants with genotype 1 or 2 chronic hepatitis C virus (HCV) infection without cirrhosis and for 12 weeks in direct-acting antiviral (DAA)-naive Japanese participants with genotype 1 or 2 chronic HCV infection with compensated cirrhosis.

Official Title
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A Phase 2a, Multicenter, Open-label Study to Investigate the Safety, Pharmacokinetics, and Efficacy of Combination Treatment of AL-335, Odalasvir, and Simeprevir in Japanese Subjects With Chronic Hepatitis C Genotype 1 or 2 Virus Infection, With or Without Compensated Cirrhosis Who Are Direct Acting Antiviral Treatment-naïve

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: AL-335
* Drug: Odalasvir (ODV)
* Drug: Simeprevir (SMV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic hepatitis C virus (HCV) infection All participants must have HCV genotype 1 or 2 infection, determined at screening HCV ribonucleic acid (RNA) plasma levels greater than or equal to (>=)10,000 international units per Milliliter (IU/mL), determined at screening Direct-acting antiviral (DAA)-naive participants, defined as not having received treatment with any approved or investigational DAA drug for chronic HCV infection; prior HCV therapy consisting of interferon (IFN, pegylated or nonpegylated) with or without ribavirin (RBV) is allowed Participants without cirrhosis or with compensated cirrhosis Exclusion Criteria: Infection with HCV genotype - 3, 4, 5, or 6 Co-infection with human immunodeficiency virus (HIV 1 or HIV 2 antibody positive) or hepatitis B virus (HBV) (hepatitis B surface antigen [HBsAg] positive) Prior treatment with any investigational or approved HCV DAA, either in combination with PegIFN or IFN free Any evidence of liver disease of non-HCV etiology. This includes, but is not limited to, acute hepatitis A infection (immunoglobulin M), drug or alcohol related liver disease, autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha 1 antitrypsin deficiency, primary biliary cirrhosis, or any other non-HCV liver disease that is considered clinically significant by the investigator Evidence of hepatic decompensation as assessed with Child-Pugh Class B or C or any of the following: history or current clinical evidence of ascites, bleeding varices, or hepatic encephalopathy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (Chronic Hepatitis C Without Cirrhosis)<br>Participants will receive 800 milligram (mg) AL-335 +odalasvir (ODV) 25 mg+simeprevir (SMV) 75 mg once daily for 8 weeks in Cohort 1. | Drug: AL-335<br>* Participants will receive AL-335 800 mg once daily for 8 weeks in cohort 1 and 12 weeks in cohort 2.<br>* Other names: JNJ-64146212;Drug: Odalasvir (ODV)<br>* Participants will receive ODV 25 mg once daily for 8 weeks in cohort 1 and 12 weeks in cohort 2.<br>* Other names: JNJ-64289901;Drug: Simeprevir (SMV)<br>* Participants will receive SMV 75 mg once daily for 8 weeks in cohort 1 and 12 weeks in cohort 2.<br>* Other names: TMC435;|
| Experimental: Cohort 2 (Chronic Hepatitis C With Compensated Cirrhosis)<br>Participants will receive AL-335 800 milligram (mg)+ODV 25 mg+SMV 75 mg once daily for 12 weeks in Cohort 2. Dosing in cohort 2 will be started according to decision of Data Review Committee (DRC). | Drug: AL-335<br>* Participants will receive AL-335 800 mg once daily for 8 weeks in cohort 1 and 12 weeks in cohort 2.<br>* Other names: JNJ-64146212;Drug: Odalasvir (ODV)<br>* Participants will receive ODV 25 mg once daily for 8 weeks in cohort 1 and 12 weeks in cohort 2.<br>* Other names: JNJ-64289901;Drug: Simeprevir (SMV)<br>* Participants will receive SMV 75 mg once daily for 8 weeks in cohort 1 and 12 weeks in cohort 2.<br>* Other names: TMC435;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | An adverse event was any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Approximately 38 weeks (Cohort 1) and 42 weeks (Cohort 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 4 Weeks (SVR4) After Actual End-of-Treatment | SVR4 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detected or not detected at 4 weeks after the actual End-of-treatment (EOT). | Week 4 (follow-up phase) | 
| Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) After Actual End-of-treatment | SVR12 was defined as HCV RNA < LLOQ (15 IU/mL) detected or not detected at 12 weeks after the actual EOT. | Week 12 (follow-up phase) | 
| Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) After Actual End-of-treatment | SVR 24 was defined as HCV RNA < LLOQ (15 IU/mL) detected or not detected at 24 weeks after the actual EOT. | Week 24 (follow-up phase) | 
| Percentage of Participants With Viral Relapse | Viral relapse was defined as participants who did not achieve SVR12, with HCV RNA < LLOQ (15 IU/mL) at the EOT and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow-up. | End of treatment up to Week 24 (follow up phase) | 
| Percentage of Participants With On-treatment Failure | On-treatment failure was defined as participants who did not achieve SVR12, with confirmed HCV RNA >= LLOQ (15 IU/mL) at the actual EOT. | EOT up to Week 12 (follow up phase) | 
| Percentage of Participants With On-treatment Virologic Response | Percentage of participants with On-treatment Virologic Response with HCV RNA < LLOQ (15 IU/mL), not detected at specified time points during treatment were reported. | Day 2, Day 3, Week 1, 2, 3, 4, 6, 8 (for Cohort 1), 10, and 12 (for Cohort 2 only) | 
| Time to Achieve HCV RNA Not Detected or HCV RNA <LLOQ | Time to Achieve HCV RNA not Detected or HCV RNA <LLOQ (15 IU/mL) was reported. | EOT up to Week 24 (follow up phase) |