Efficacy and Safety of Combinations of AL-335, Odalasvir (ODV) and Simeprevir (SMV) in the Treatment of Chronic Hepatitis C Infection

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy (proportion of subjects with SVR12), safety, tolerability and pharmacokinetics of an 8- and 6-week treatment regimen of AL-335, odalasvir (ODV) and simeprevir (SMV) in chronic HCV genotype 1, 2, 4, 5 or 6 infected subjects without cirrhosis.

Detailed Description
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This is a Phase 2b multicenter study. The study will include a screening period of maximum 6 weeks, a treatment period of 6 or 8 weeks and a 24-weeks post-treatment follow-up period. The total study duration for each subject will be 36 to 38 weeks. This study investigates a 3 direct-acting antiviral agent (DAA) combination of AL-335 (HCV NS5B inhibitor), odalasvir (ODV) (a second generation HCV NS5A inhibitor) and simeprevir (SMV) (HCV NS3A4 protease inhibitor). The results of this study will enable the selection of treatment and duration to be further developed.

Official Title
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A Phase 2b, Multicenter, Randomized, Open-label Study to Investigate the Efficacy, Safety and Pharmacokinetics of Different Treatment Regimens of AL-335, Odalasvir, and Simeprevir in Treatment-naive and Treatment-experienced Subjects With Chronic Hepatitis C Virus Genotype 1, 2, 4, 5, and 6 Infection Without Cirrhosis

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: AL-335
* Drug: Odalasvir
* Drug: Simeprevir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals with chronic hepatitis C virus (HCV) genotype 1, 2, 4, 5 or 6 infection Documented as treatment naive or experienced with a prior regimen consisting of Interferon (IFN) +/-Ribavirin (RBV) regimen without achieving sustained viral response Absence of cirrhosis Screening laboratory values within defined thresholds Must use specific contraceptive methods if female of childbearing potential or sexually active male Exclusion Criteria: Co-infection with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) Prior exposure to an HCV direct-acting antiviral agent (DAA), either in combination with pegylated interferon (PegIFN) or IFN-free Current or prior history of clinical hepatic decompensation History of clinically significant illness or any other medical disorder including cardiovascular conditions that may interfere with individual's treatment, assessment or compliance with the protocol Pregnant or a nursing female

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>AL-335 (800 mg), odalasvir (25 mg) and simeprevir (75 mg) once daily during 6 weeks. | Drug: AL-335<br>* AL-335 800 mg (2*400) tablet will be administered once daily.<br>Drug: Odalasvir<br>* Odalasvir 25 mg tablet will be administered once daily.<br>Drug: Simeprevir<br>* Simeprevir 75 mg capsule will be administered once daily.<br>|
| Experimental: Group B<br>AL-335 (800 mg), odalasvir (25 mg) and simeprevir (75 mg) once daily during 8 weeks. | Drug: AL-335<br>* AL-335 800 mg (2*400) tablet will be administered once daily.<br>Drug: Odalasvir<br>* Odalasvir 25 mg tablet will be administered once daily.<br>Drug: Simeprevir<br>* Simeprevir 75 mg capsule will be administered once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12) | The SVR 12 was defined as 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. | Week 12 (Follow-Up Phase) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Treatment (SVR24) | The SVR24 was defined as HCV RNA <LLOQ (detectable or undetectable) 24 weeks after End of Treatment (EOT). | Week 24 (Follow-Up Phase) | 
| Number of Participants With Viral Relapse | Viral Relapse: Participants who did not achieve SVR12, with HCV RNA <LLOQ 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) | 
| Number of Participants With Late Viral Relapse | Late Viral Relapse: Participants who achieved SVR12 but had confirmed HCV RNA>=LLOQ afterwards during follow-up. | Up to Week 24 (Follow-up Phase) | 
| Percentage of Participants With On-treatment Failure | On-treatment failure: Participants who did not achieve SVR12 and with confirmed HCV RNA>=LLOQ at the End of Treatment (EOT). | EOT up to Week 12 (Follow up Phase) | 
| Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Treatment (EOT) | The SVR 4 was defined as participants were considered to have reached SVR4, if 4 weeks after the actual EOT, HCV RNA was <LLOQ (detectable or undetectable). | Week 4 (Follow-Up Phase) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AL-335, Hepatitis C, Chronic, Odalasvir, Simeprevir, ODV, SMV, ACH-3102, ACH-0143102, TMC435