Safety, Tolerability and Antiviral Activity of ACH-0141625 or Placebo in Combination With Peginterferon and Ribavirin in HCV Positive Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Achillion Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01180790
First received: August 11, 2010
Last updated: September 8, 2014
Last verified: September 2014

August 11, 2010
September 8, 2014
September 2010
March 2012   (final data collection date for primary outcome measure)
  • Segment 1: Safety [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    Segment 1: Percentage of subjects with the following: adverse events, abnormal laboratory safety tests, dose reductions, interruptions, and discontinuations. Criteria for abnormal laboratory safety tests: treatment-emergent worsening DAIDs graded laboratory tests.
  • Segment 1 : Rapid Viral Response at Week 4 (RVR4) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    The primary efficacy endpoint for Segment 1 of the study was the percentage of subjects in each treatment group achieving RVR at Week 4 (HCV RNA< or equal to LOQ at the Week 4 visit).
  • Segment 2: Safety [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Segment 2: Percentage of Subjects 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.
  • Segment 2: Complete Early Virologic Response (cEVR) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    The primary efficacy endpoint for Segment 2 of the study was the percentage of subjects achieving cEVR (complete early virologic response), defined as undetectable HCV RNA at Week 12.
  • Safety [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    Adverse events, serious adverse events, physical exam findings, clinical laboratory results, vital sign assessments and ECG assessments
  • Rapid Viral Response at 4 weeks [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    Adverse events, serious adverse events, physical exam findings, clinical laboratory assessments, vital signs assessments and ECG findings.
Complete list of historical versions of study NCT01180790 on ClinicalTrials.gov Archive Site
  • Segment 1: Complete Early Virologic Response (cEVR) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    For Segment 1, the percentage of subjects in the virology population that achieved cEVR (complete early virologic response), defined as undetectable HCV RNA at Week 12.
  • Segment 2: RVR4 (Rapid Viral Response at 4 Weeks) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    For Segment 2, the percentage of subjects in the virology population that achieved RVR4, defined as HCV RNA< or equal to LOQ at the Week 4 visit.
  • Segment 1 and Segment 2: End of Treatment Response [ Time Frame: Week 48 (Segment 1); Week 24 (Segment 2) ] [ Designated as safety issue: No ]
    The percentage of the Virology Population subjects that were reported as undetectable HCV RNA at the completion of treatment.
  • Segment 1 and Segment 2: Sustained Virologic Response 12 Weeks ( Three Months Post Dosing) (SVR12) [ Time Frame: 3 months post dosing ] [ Designated as safety issue: No ]
    The percentage of the Virology Population subjects that achieved sustained virologic response, defined as HCV RNA < LOQ, at 12 weeks (three months) post dosing.
  • Segment 1 and Segment 2: Sustained Virologic Response ( Six Months Post Dosing) (SVR24) [ Time Frame: 6 months post dosing ] [ Designated as safety issue: No ]
    The percentage of the Virology Population subjects that achieved sustained virologic response, defined as HCV RNA < LOQ, six months post dosing.
  • Segment 1 and Segment 2: HCV RNA Change From Baseline [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    The mean change from baseline in log10 HCV RNA level by visit for the virology population
  • Segment 1 and Segment 2: HCV RNA Change From Baseline [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Change from baseline in log10 HCV RNA level by visit.
  • Early virologic response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Complete early virologic response [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • End of treatment response [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Sustained virologic response [ Time Frame: Week 60 ] [ Designated as safety issue: No ]
  • Sustained virologic response [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  • Time to undetectable HCV RNA [ Time Frame: 1 to 28 days ] [ Designated as safety issue: No ]
  • HCV RNA change from baseline [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  • HCV RNA change from baseline [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • HCV RNA change from baseline [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • HCV RNA change from baseline [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • HCV RNA change from baseline [ Time Frame: Week 60 ] [ Designated as safety issue: No ]
  • HCV RNA change from baseline [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Safety, Tolerability and Antiviral Activity of ACH-0141625 or Placebo in Combination With Peginterferon and Ribavirin in HCV Positive Subjects
A Phase IIa, Randomized, Double-blind (Subject 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 Subjects With Chronic Hepatitis C Virus Genotype 1

Evaluate safety, tolerability and antiviral response of ACH-0141625 compared to Standard of Care in HCV positive subjects.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Hepatitis C
  • Drug: ACH-0141625 (Sovaprevir)
    200 mg oral capsule once daily
  • Drug: ACH-0141625 (Sovaprevir)
    400 mg oral capsule once daily
  • Drug: ACH-0141625 (Sovaprevir)
    800 mg oral capsule once daily
  • Drug: Placebo
    Powder in capsule once daily
  • Drug: Pegylated Interferon alpha-2a
    180 ug once a week by subcutaneous injection
    Other Name: Peg-INF
  • Drug: Ribavirin
    400 mg or 600 mg (am) and 600 mg (pm) capsules taken orally twice daily
    Other Names:
    • Ribasphere
    • Copegus
  • Experimental: Segment 1: 200 mg ACH-0141625
    200 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a and ribavirin for 48 weeks
    Interventions:
    • Drug: ACH-0141625 (Sovaprevir)
    • Drug: Pegylated Interferon alpha-2a
    • Drug: Ribavirin
  • Experimental: Segment 1: 400 mg ACH-0141625
    400 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus ribavirin for 48 weeks
    Interventions:
    • Drug: ACH-0141625 (Sovaprevir)
    • Drug: Pegylated Interferon alpha-2a
    • Drug: Ribavirin
  • Experimental: Segment 1: 800 mg ACH-0141625
    800 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus ribavirin for 48 weeks
    Interventions:
    • Drug: ACH-0141625 (Sovaprevir)
    • Drug: Pegylated Interferon alpha-2a
    • Drug: Ribavirin
  • Placebo Comparator: Segment 1: Placebo
    Placebo for 28 days plus Peg-IFN alpha-2a plus ribavirin for 48 weeks
    Interventions:
    • Drug: Placebo
    • Drug: Pegylated Interferon alpha-2a
    • Drug: Ribavirin
  • Experimental: Segment 2: 200 mg ACH-0141625
    200 mg ACH-0141625 for 12 weeks plus Peg-IFN and ribavirin for up to a total of 24 or 48 weeks
    Interventions:
    • Drug: ACH-0141625 (Sovaprevir)
    • Drug: Pegylated Interferon alpha-2a
    • Drug: Ribavirin
  • Experimental: Segment 2 : 400 mg ACH-0141625
    400 mg ACH-0141625 for 12 weeks plus Peg-IFN and ribavirin for up to a total of 24 or 48 weeks
    Interventions:
    • Drug: ACH-0141625 (Sovaprevir)
    • Drug: Pegylated Interferon alpha-2a
    • Drug: Ribavirin
  • Experimental: Segment 2 : 800 mg ACH-0141625
    800 mg ACH-0141625 for 12 weeks plus Peg-IFN and ribavirin for up to a total of 24 or 48 weeks
    Interventions:
    • Drug: ACH-0141625 (Sovaprevir)
    • Drug: Pegylated Interferon alpha-2a
    • Drug: Ribavirin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
122
April 2013
March 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Males and females 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 FSH at screening. Females of child bearing 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 six months following the discontinuation of SOC.
  • Fertile males must agree to use a condom and his female partner must agree to use one or more methods of contraception. Males must not donate sperm during the study and three months following the last exposure to RBV.

Exclusion Criteria:

  • BMI >36 kg/m2
  • 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 HBV and/or HIV
  • Other significant disease 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 one 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 first dose of study drug.
  • Have a clinically significant laboratory abnormality at screening (as specified in protocol).
  • Segment 1: Subjects with any history of decompensated liver disease defined as cirrhotic subjects with a Child-Pugh score of > or = to 7. Segment 2: Subjects 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.
  • Subjects, who prematurely discontinued, interrupted or dose reduced prior Peg-IFN and Ribavirin 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 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 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 protocol)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium
 
NCT01180790
ACH625-003, 2010-022092-65
Not Provided
Achillion Pharmaceuticals
Achillion Pharmaceuticals
Not Provided
Study Director: Hetal Kocinsky, MD Achillion Pharmaceuticals
Achillion Pharmaceuticals
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP