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

Alexion Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Hepatitis C

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01180790

ACH625-003

2010-022092-65 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 122 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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122 participants in 7 patient groups, including a placebo group

Segment 1: 200 milligrams (mg) ACH-0141625

Experimental group

Description:

200 mg ACH-0141625 for 28 days plus pegylated interferon (Peg-IFN) alpha-2a and ribavirin (RBV) for 48 weeks

Treatment:

Drug: ACH-0141625 (Sovaprevir)

Drug: Pegylated Interferon alpha-2a

Drug: ACH-0141625 (Sovaprevir)

Drug: ACH-0141625 (Sovaprevir)

Drug: Ribavirin

Segment 1: 400 mg ACH-0141625

Experimental group

Description:

400 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks

Treatment:

Drug: ACH-0141625 (Sovaprevir)

Drug: Pegylated Interferon alpha-2a

Drug: ACH-0141625 (Sovaprevir)

Drug: ACH-0141625 (Sovaprevir)

Drug: Ribavirin

Segment 1: 800 mg ACH-0141625

Experimental group

Description:

800 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks

Treatment:

Drug: ACH-0141625 (Sovaprevir)

Drug: Pegylated Interferon alpha-2a

Drug: ACH-0141625 (Sovaprevir)

Drug: ACH-0141625 (Sovaprevir)

Drug: Ribavirin

Segment 1: Placebo

Placebo Comparator group

Description:

Placebo for 28 days plus Peg-IFN alpha-2a plus RBV for 48 weeks

Treatment:

Drug: Pegylated Interferon alpha-2a

Drug: Placebo

Drug: Ribavirin

Segment 2: 200 mg ACH-0141625

Experimental group

Description:

200 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks

Treatment:

Drug: ACH-0141625 (Sovaprevir)

Drug: Pegylated Interferon alpha-2a

Drug: ACH-0141625 (Sovaprevir)

Drug: ACH-0141625 (Sovaprevir)

Drug: Ribavirin

Segment 2 : 400 mg ACH-0141625

Experimental group

Description:

400 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks

Treatment:

Drug: ACH-0141625 (Sovaprevir)

Drug: Pegylated Interferon alpha-2a

Drug: ACH-0141625 (Sovaprevir)

Drug: ACH-0141625 (Sovaprevir)

Drug: Ribavirin

Segment 2 : 800 mg ACH-0141625

Experimental group

Description:

800 mg ACH-0141625 for 12 weeks plus Peg-IFN and RBV for up to a total of 24 or 48 weeks

Treatment:

Drug: ACH-0141625 (Sovaprevir)

Drug: Pegylated Interferon alpha-2a

Drug: ACH-0141625 (Sovaprevir)

Drug: ACH-0141625 (Sovaprevir)

Drug: Ribavirin