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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: Placebo; Drug: Ribavirin; Drug: Sovaprevir; Drug: ACH-3102

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M6H3M1
      • Toronto Liver Centre
• United States
  • California
    • Bakersfield, California, United States, 93301
      • Franco Felizarta
    • La Mesa, California, United States, 91942
      • eStudy Site
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia
  • Tennessee
    • Nashville, Tennessee, United States, 78215
      • Nashville Gastrointestinal Specialists
  • Texas
    • Houston, Texas, United States, 77030
      • Liver Associates of Texas PA
    • San Antonio, Texas, United States, 78215
      • American Research Corporation
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • Medical Associates of Central Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sovaprevir 200 milligrams (mg), ACH-3102 150/50 mg, RBV 1000-1200 mg; 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: Ribavirin; Drug: Sovaprevir; Nonstructural protein 3/4A protease inhibitor.; Other Names: ACH-0141625; Drug: ACH-3102; Nonstructural protein 5A inhibitor.
Active Comparator: Sovaprevir 400 mg, ACH-3102 150/50 mg, RBV 1000 -1200 mg; 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: Ribavirin; Drug: Sovaprevir; Nonstructural protein 3/4A protease inhibitor.; Other Names: ACH-0141625; Drug: ACH-3102; Nonstructural protein 5A inhibitor.
Placebo Comparator: Placebo; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alexion
• Collaborators: Achillion, a wholly owned subsidiary of Alexion

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: April 18, 2013
• First Submitted That Met QC Criteria: May 7, 2013
• First Posted (Estimated): May 8, 2013

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Antiviral Agents; Chronic Hepatitis C; Hepatitis C; Hepatitis; Protease Inhibitors; Liver Diseases; Ribavirin; Genotype 1; Viral; Anti-infective Agents; NS5a Inhibitors
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Chronic Disease; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Odalasvir
• Other Study ID Numbers: ACH102-007