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

Phase 2

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Group A	AL-335	AL-335 (800 mg), odalasvir (25 mg) and simeprevir (75 mg) once daily during 6 weeks.
Group B	AL-335	AL-335 (800 mg), odalasvir (25 mg) and simeprevir (75 mg) once daily during 8 weeks.
Group A	Simeprevir	AL-335 (800 mg), odalasvir (25 mg) and simeprevir (75 mg) once daily during 6 weeks.
Group B	Odalasvir	AL-335 (800 mg), odalasvir (25 mg) and simeprevir (75 mg) once daily during 8 weeks.
Group B	Simeprevir	AL-335 (800 mg), odalasvir (25 mg) and simeprevir (75 mg) once daily during 8 weeks.
Group A	Odalasvir	AL-335 (800 mg), odalasvir (25 mg) and simeprevir (75 mg) once daily during 6 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)	Week 12 (Follow-Up Phase)	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Treatment (SVR24)	Week 24 (Follow-Up Phase)	The SVR24 was defined as HCV RNA \<LLOQ (detectable or undetectable) 24 weeks after End of Treatment (EOT).
Number of Participants With Viral Relapse	End of Treatment up to Week 24 (Follow up phase)	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.
Number of Participants With Late Viral Relapse	Up to Week 24 (Follow-up Phase)	Late Viral Relapse: Participants who achieved SVR12 but had confirmed HCV RNA\>=LLOQ afterwards during follow-up.
Percentage of Participants With On-treatment Failure	EOT up to Week 12 (Follow up Phase)	On-treatment failure: Participants who did not achieve SVR12 and with confirmed HCV RNA\>=LLOQ at the End of Treatment (EOT).
Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Treatment (EOT)	Week 4 (Follow-Up Phase)	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).