Safety, Tolerability, and Antiviral Activity of ACH-0141625 or Placebo in Combination With Peginterferon and Ribavirin in Hepatitis C Virus (HCV) Positive Participants

Study Overview
=================
Brief Summary
-----------------
Evaluate safety, tolerability, and antiviral response of ACH-0141625 compared to standard of care in hepatitis C virus (HCV)-positive participants.

Official Title
-----------------
A Phase IIa, Randomized, Double-blind (Participant and Investigator Blind, Sponsor Open), Placebo-controlled Trial to Evaluate the Safety, Tolerability, and Antiviral Activity of Oral ACH-0141625 in Combination With Pegylated Interferon Alpha-2a and Ribavirin in Two Segments, After 28 Days of Dosing and, Subsequently, After 12 Weeks of Dosing in Participants With Chronic Hepatitis C Virus Genotype 1

Conditions
-----------------
Hepatitis C

Intervention / Treatment
-----------------
* Drug: ACH-0141625 (Sovaprevir)
* Drug: ACH-0141625 (Sovaprevir)
* Drug: ACH-0141625 (Sovaprevir)
* Drug: Placebo
* Drug: Pegylated Interferon alpha-2a
* Drug: Ribavirin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females, aged 18 years and older Chronic hepatitis C genotype 1 (as specified in the protocol) Treatment naive Females who are post-menopausal and amenorrheic must have a follicle-stimulating hormone (FSH) at screening. Females of childbearing potential must have a negative pregnancy test at screening and baseline. Females must use a non-hormonal method of contraception and must agree not to get pregnant during the study and for 6 months following the discontinuation of standard of care (SOC). Fertile males must agree to use a condom and his female partner must agree to use 1 or more methods of contraception. Males must not donate sperm during the study and 3 months following the last exposure to RBV. Exclusion Criteria: Body mass index (BMI) >36 kilograms (kg)/square meter (m^2) Pregnant or nursing females or females of childbearing potential not willing to comply with contraceptive measures per protocol. Men whose female partners are pregnant or contemplating pregnancy. - Coinfection with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) Other significant diseases including liver disease History of drug or alcohol dependence or addiction within the past 6 months History of participation in a clinical trial with a protease inhibitor or previous treatment with a protease inhibitor, where at least 1 dose of the protease inhibitor was consumed. Use of herbal or homeopathic products, illicit drugs, cytochrome P450 (CYP) 3A4/5 substrates, inducers or inhibitors, hormonal methods of contraception, corticosteroids, immunosuppressive, or cytotoxic agents within 28 days of the first dose of study drug. Have a clinically significant laboratory abnormality at screening (as specified in the protocol). Segment 1: Participants with any history of decompensated liver disease defined as cirrhotic participants with a Child-Pugh score of > or = to 7. Segment 2: Participants who have had a liver biopsy that shows bridging fibrosis or cirrhosis. Nonalcoholic steatohepatitis if ballooning degeneration or Mallory bodies are present on liver biopsy. Participants who prematurely discontinued, interrupted, or dose reduced prior Peg-IFN and RBV therapy due to noncompliance or safety issues. Encephalopathy or altered mental status of any etiology. History of moderate, severe, or uncontrolled psychiatric disease (as specified in the protocol). History of malignancy of any organ system treated or untreated within the past 5 years. Use of colony stimulating factor agents within 90 days prior to baseline. History of seizure disorder. History of known coagulopathy including hemophilia. Clinically of significant findings on fundoscopic or retinal examination at screening History of immunologically mediate disease. History of clinical evidence of chronic cardiac disease (as specified in the protocol) Received concomitant systemic antibiotic, antifungals, or antivirals for the treatment of active infection within 14 days prior to the first dose of the study drug (as specified in the protocol)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Segment 1: 200 milligrams (mg) ACH-0141625<br>200 mg ACH-0141625 for 28 days plus pegylated interferon (Peg-IFN) alpha-2a and ribavirin (RBV) for 48 weeks | Drug: ACH-0141625 (Sovaprevir)<br>* 200 mg oral capsule once daily<br>Drug: Pegylated Interferon alpha-2a<br>* 180 micrograms (ug) once a week by subcutaneous injection<br>* Other names: Peg-INF;Drug: Ribavirin<br>* 400 mg or 600 mg (morning [AM]) and 600 mg (evening [PM]) capsules taken orally twice daily<br>* Other names: Copegus;|
| Experimental: Segment 1: 400 mg ACH-0141625<br>400 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks | Drug: ACH-0141625 (Sovaprevir)<br>* 400 mg oral capsule once daily<br>Drug: Pegylated Interferon alpha-2a<br>* 180 micrograms (ug) once a week by subcutaneous injection<br>* Other names: Peg-INF;Drug: Ribavirin<br>* 400 mg or 600 mg (morning [AM]) and 600 mg (evening [PM]) capsules taken orally twice daily<br>* Other names: Copegus;|
| Experimental: Segment 1: 800 mg ACH-0141625<br>800 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks | Drug: ACH-0141625 (Sovaprevir)<br>* 800 mg oral capsule once daily<br>Drug: Pegylated Interferon alpha-2a<br>* 180 micrograms (ug) once a week by subcutaneous injection<br>* Other names: Peg-INF;Drug: Ribavirin<br>* 400 mg or 600 mg (morning [AM]) and 600 mg (evening [PM]) capsules taken orally twice daily<br>* Other names: Copegus;|
| Placebo Comparator: Segment 1: Placebo<br>Placebo for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks | Drug: Placebo<br>* Powder in capsule once daily<br>Drug: Pegylated Interferon alpha-2a<br>* 180 micrograms (ug) once a week by subcutaneous injection<br>* Other names: Peg-INF;Drug: Ribavirin<br>* 400 mg or 600 mg (morning [AM]) and 600 mg (evening [PM]) capsules taken orally twice daily<br>* Other names: Copegus;|
| Experimental: Segment 2: 200 mg ACH-0141625<br>200 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks | Drug: ACH-0141625 (Sovaprevir)<br>* 200 mg oral capsule once daily<br>Drug: Pegylated Interferon alpha-2a<br>* 180 micrograms (ug) once a week by subcutaneous injection<br>* Other names: Peg-INF;Drug: Ribavirin<br>* 400 mg or 600 mg (morning [AM]) and 600 mg (evening [PM]) capsules taken orally twice daily<br>* Other names: Copegus;|
| Experimental: Segment 2 : 400 mg ACH-0141625<br>400 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks | Drug: ACH-0141625 (Sovaprevir)<br>* 400 mg oral capsule once daily<br>Drug: Pegylated Interferon alpha-2a<br>* 180 micrograms (ug) once a week by subcutaneous injection<br>* Other names: Peg-INF;Drug: Ribavirin<br>* 400 mg or 600 mg (morning [AM]) and 600 mg (evening [PM]) capsules taken orally twice daily<br>* Other names: Copegus;|
| Experimental: Segment 2 : 800 mg ACH-0141625<br>800 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks | Drug: ACH-0141625 (Sovaprevir)<br>* 800 mg oral capsule once daily<br>Drug: Pegylated Interferon alpha-2a<br>* 180 micrograms (ug) once a week by subcutaneous injection<br>* Other names: Peg-INF;Drug: Ribavirin<br>* 400 mg or 600 mg (morning [AM]) and 600 mg (evening [PM]) capsules taken orally twice daily<br>* Other names: Copegus;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Segment 1: Safety | Segment 1: Percentage of participants with the following: adverse events, abnormal laboratory safety tests, dose reductions, interruptions, and discontinuations. Criteria for abnormal laboratory safety tests: treatment-emergent worsening Division of AIDS (Acquired Immunodeficiency Syndrome) (DAIDs) graded laboratory tests. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | 4 weeks | 
| Segment 1: Rapid Viral Response At Week 4 (RVR4) | The primary efficacy endpoint for Segment 1 of the study was the percentage of participants in each treatment group achieving RVR4 (hepatitis C virus [HCV] ribonucleic acid (RNA) less than or equal to the limit of quantitation [LOQ] at the Week 4 visit). | 4 weeks | 
| Segment 2: Safety | Segment 2: Percentage of participants with the following: adverse events, abnormal laboratory safety tests and dose reductions, interruptions and discontinuations. Criteria for abnormal laboratory safety tests: treatment-emergent worsening DAIDs graded laboratory tests. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. | 12 weeks | 
| Segment 2: Complete Early Virologic Response (cEVR) | The primary efficacy endpoint for Segment 2 of the study was the percentage of participants achieving cEVR, defined as undetectable HCV RNA at Week 12. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Segment 1: cEVR | For Segment 1, the percentage of participants in the virology population who achieved cEVR, defined as undetectable HCV RNA at Week 12. | 12 weeks | 
| Segment 2: RVR4 | For Segment 2, the percentage of participants in the virology population who achieved RVR4, defined as HCV RNA less than or equal to the LOQ at the Week 4 visit. | 4 weeks | 
| Segment 1 And Segment 2: End Of Treatment Response | The percentage of virology population participants who were reported as undetectable HCV RNA at the completion of treatment. | Week 48 (Segment 1); Week 24 (Segment 2) | 
| Segment 1 And Segment 2: Sustained Virologic Response 12 Weeks (3 Months Post-dosing) (SVR12) | The percentage of virology population participants who achieved sustained virologic response (SVR), defined as HCV RNA less than the LOQ, at 12 weeks (3 months) post-dosing. | 3 months post-dosing | 
| Segment 1 And Segment 2: Sustained Virologic Response 24 Weeks (6 Months Post-dosing) (SVR24) | The percentage of virology population participants who achieved SVR, defined as HCV RNA less than the LOQ, 6 months post-dosing. | 6 months post-dosing | 
| Segment 1 And Segment 2: HCV RNA Change From Baseline | The mean change from baseline in log10 HCV RNA level by visit for the virology population | Week 4 | 
| Segment 1 And Segment 2: HCV RNA Change From Baseline | Change from baseline in log10 HCV RNA level by visit. | Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HCV, Hepatitis C Genotype 1