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

Phase 2

Completed

Conditions: Hepatitis C

Interventions: Drug: ACH-0141625 (Sovaprevir)
Drug: Placebo
Drug: Pegylated Interferon alpha-2a
Drug: Ribavirin

Registration Number: NCT01180790

Lead Sponsor: Alexion Pharmaceuticals, Inc.

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 122

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Segment 2 : 800 mg ACH-0141625	ACH-0141625 (Sovaprevir)	800 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
Segment 1: 800 mg ACH-0141625	ACH-0141625 (Sovaprevir)	800 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
Segment 2: 200 mg ACH-0141625	ACH-0141625 (Sovaprevir)	200 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
Segment 2 : 400 mg ACH-0141625	ACH-0141625 (Sovaprevir)	400 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
Segment 1: 200 milligrams (mg) ACH-0141625	ACH-0141625 (Sovaprevir)	200 mg ACH-0141625 for 28 days plus pegylated interferon (Peg-IFN) alpha-2a and ribavirin (RBV) for 48 weeks
Segment 1: 400 mg ACH-0141625	ACH-0141625 (Sovaprevir)	400 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
Segment 1: Placebo	Placebo	Placebo for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
Segment 1: 200 milligrams (mg) ACH-0141625	Pegylated Interferon alpha-2a	200 mg ACH-0141625 for 28 days plus pegylated interferon (Peg-IFN) alpha-2a and ribavirin (RBV) for 48 weeks
Segment 1: 200 milligrams (mg) ACH-0141625	Ribavirin	200 mg ACH-0141625 for 28 days plus pegylated interferon (Peg-IFN) alpha-2a and ribavirin (RBV) for 48 weeks
Segment 1: 400 mg ACH-0141625	Pegylated Interferon alpha-2a	400 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
Segment 1: 800 mg ACH-0141625	Ribavirin	800 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
Segment 1: 400 mg ACH-0141625	Ribavirin	400 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
Segment 1: 800 mg ACH-0141625	Pegylated Interferon alpha-2a	800 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
Segment 1: Placebo	Pegylated Interferon alpha-2a	Placebo for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
Segment 1: Placebo	Ribavirin	Placebo for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks
Segment 2: 200 mg ACH-0141625	Pegylated Interferon alpha-2a	200 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
Segment 2: 200 mg ACH-0141625	Ribavirin	200 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
Segment 2 : 400 mg ACH-0141625	Pegylated Interferon alpha-2a	400 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
Segment 2 : 800 mg ACH-0141625	Pegylated Interferon alpha-2a	800 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
Segment 2 : 400 mg ACH-0141625	Ribavirin	400 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks
Segment 2 : 800 mg ACH-0141625	Ribavirin	800 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks

Primary Outcome Measures

Name	Time	Method
Segment 2: Complete Early Virologic Response (cEVR)	Week 12	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.
Segment 1: Rapid Viral Response At Week 4 (RVR4)	4 weeks	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).
Segment 2: Safety	12 weeks	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.
Segment 1: Safety	4 weeks	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.

Secondary Outcome Measures

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