Safety, Tolerability, and Efficacy of 12-weeks of Sovaprevir, ACH-3102, and Ribavirin in Treatment-naive GT-1 HCV Participants

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the safety, tolerability, and efficacy of 12 weeks of treatment with sovaprevir, ACH-0143102, and ribavirin (RBV) in genotype-1 (GT-1), treatment-naive, hepatitis C virus (HCV) participants.

Official Title
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A Phase 2a Trial to Evaluate the Safety, Tolerability, and Efficacy of 12 Weeks of Sovaprevir, ACH-0143102 and Ribavirin in Treatment-Naive Subjects With Chronic Hepatitis C Genotype-1 Viral Infection

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Sovaprevir
* Drug: ACH-3102
* Drug: Ribavirin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic HCV infection. HCV GT-1. HCV ribonucleic acid > 10,000 international units/milliliter at screening. Female participants must be willing to use 2 effective methods of contraception, one of which must be a barrier method, during the dosing period and 6 months after the last dose of RBV. Females of childbearing potential must have a negative pregnancy test at screening and baseline. Male participants must be willing to use an effective barrier method of contraception throughout the dosing period and for 6 months. Signed and dated written informed consent form. Willing to participate in all study activities and all study requirements (including effective contraception) during the study period. Treatment-naïve participants were defined as those participants who have never received pegylated interferon, RBV, or a direct-acting anti-viral agent for the treatment of chronic HCV infection. A liver biopsy within the last 3 years without evidence of cirrhosis. Exclusion Criteria: Body mass index > 36.0 kilograms/meter squared. Pregnant or nursing (lactating) female participants confirmed by a positive human chorionic gonadotropin laboratory test or contemplating pregnancy. Participation in any interventional clinical trial within 35 days prior to first study medication dose administration on Day 1. Known human immunodeficiency virus (HIV)-1 or HIV-2 infection/serology and/or positive hepatitis B surface antigen. Use of dietary supplements, grapefruit juice, herbal supplements, cytochrome P450 (CYP) 2C8 substrates, CYP3A4 inducers and inhibitors, P-glycoprotein inducers and substrates, organic-anion-transporting polypeptide inhibitors and substrates, and potent inducers of other CYP enzymes within 14 days prior to dosing through 7 days following completion of study medications. Clinically significant laboratory abnormality at screening (specified in protocol). Other forms of liver disease. History of severe or uncontrolled psychiatric disease. History of malignancy of any organ system, treated or untreated within the past 5 years. History of major organ transplantation. Use of bone marrow colony stimulating factor agents within 3 months prior to baseline. History of seizure disorder requiring ongoing medical therapy. History of known coagulopathy including hemophilia. History of hemoglobinopathy, including sickle cell anemia and thalassemia. History of immunologically mediated disease (specified in protocol). History of clinical evidence of significant chronic cardiac disease ( specified in protocol). Electrocardiogram with any clinically significant abnormality. Structural or functional cardiac abnormalities (specified in protocol). History of chronic obstructive pulmonary disease, emphysema, or other chronic lung disease. Participants currently abusing amphetamines, cocaine or opiates, or with ongoing alcohol abuse in the judgement of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sovaprevir 200 milligrams (mg), ACH-3102 150/50 mg, RBV 1000-1200 mg<br>Sovaprevir 200 mg once daily (qd) + ACH-3102 150 mg loading dose on Day 1, followed by 50 mg qd + RBV weight-based 1000-1200 mg qd for 12 weeks. | Drug: Sovaprevir<br>* Nonstructural protein 3/4A protease inhibitor.<br>* Other names: ACH-0141625;Drug: ACH-3102<br>* Nonstructural protein 5A inhibitor.<br>Drug: Ribavirin<br> <br> |
| Active Comparator: Sovaprevir 400 mg, ACH-3102 150/50 mg, RBV 1000 -1200 mg<br>Sovaprevir 400 mg qd + ACH-3102 150 mg loading dose on Day 1, followed by 50 mg qd + RBV weight-based 1000-1200 mg qd for 12 weeks. | Drug: Sovaprevir<br>* Nonstructural protein 3/4A protease inhibitor.<br>* Other names: ACH-0141625;Drug: ACH-3102<br>* Nonstructural protein 5A inhibitor.<br>Drug: Ribavirin<br> <br> |
| Placebo Comparator: Placebo<br>Placebo for sovaprevir capsule qd + placebo for ACH-3102 150 mg loading dose on Day 1, followed by placebo for 50 mg qd + placebo for weight-based RBV qd for 12 weeks. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence Of Sustained Virologic Response 4 Weeks (SVR4) After The Completion Of Treatment | Incidence of SVR4 after the completion of dosing, reported as hepatitis C virus (HCV) ribonucleic acid less than the lower limit of quantification, in participants who received active treatment (sovaprevir and ACH-0143102 in combination with RBV) as compared to those who received placebo. | Four weeks after the completion of treatment | 
| Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants | To determine the safety and tolerability of 12 weeks of sovaprevir/ACH-0143102/RBV treatment in participants with chronic genotype-1 (GT-1) HCV, the following criteria will be used: the number of participants with discontinuations due to adverse events (AEs), treatment-emergent Grade 3/Grade 4 (G3/G4) AEs, treatment-emergent G3/G4 laboratory abnormalities, and clinically significant electrocardiograms (ECGs). | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genotype 1, Hepatitis C, Liver Diseases, Hepatitis, Ribavirin, Antiviral Agents, Anti-infective Agents, Protease Inhibitors, NS5a Inhibitors, Viral, Chronic Hepatitis C