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
  Purpose

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


Condition Intervention Phase
Hepatitis C
Drug: ACH-0141625 (Sovaprevir)
Drug: Placebo
Drug: Pegylated Interferon alpha-2a
Drug: Ribavirin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Achillion Pharmaceuticals:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 122
Study Start Date: September 2010
Study Completion Date: April 2013
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Segment 1: 200 mg ACH-0141625
200 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a and ribavirin for 48 weeks
Drug: ACH-0141625 (Sovaprevir)
200 mg oral 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: 400 mg ACH-0141625
400 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus ribavirin for 48 weeks
Drug: ACH-0141625 (Sovaprevir)
400 mg oral 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: 800 mg ACH-0141625
800 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus ribavirin for 48 weeks
Drug: ACH-0141625 (Sovaprevir)
800 mg oral 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
Placebo Comparator: Segment 1: Placebo
Placebo for 28 days plus Peg-IFN alpha-2a plus ribavirin for 48 weeks
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 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
Drug: ACH-0141625 (Sovaprevir)
200 mg oral 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 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
Drug: ACH-0141625 (Sovaprevir)
400 mg oral 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 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
Drug: ACH-0141625 (Sovaprevir)
800 mg oral 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01180790

Locations
United States, California
Axis Clinical Trials
Los Angeles, California, United States, 90036
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Quest Clinical Research
San Francisco, California, United States, 94115
United States, Florida
Pointe West Infectious Disease
Brandenton, Florida, United States, 34209
Orlando Immunology Center
Orlando, Florida, United States, 32803
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Kansas
Vince and Associates Clinical Research
Overland Park, Kansas, United States, 66211
United States, Missouri
St. Louis University
St. Louis, Missouri, United States, 63104
United States, Nevada
Impact Clinical Trials
Las Vegas, Nevada, United States, 89106
United States, New York
Weill Medical College of Cornell University
New York, New York, United States, 10065
United States, Pennsylvania
Albert Einstein Medical Center
Philadelphia, Pennsylvania, United States, 19141
United States, Texas
North Texas Research Institute
Arlington, Texas, United States, 76012
Alamo Medical Research
San Antonio, Texas, United States, 78215
United States, Virginia
Bon Secours St. Mary's Hospital of Richmond
Newport News, Virginia, United States, 23602
Digestive and Liver Diseas Specialists
Norfolk, Virginia, United States, 23502
Belgium
Universitair Ziekenhuis Antwerpen
Edgem, Antwerp, Belgium, 2650
Centre Hospitalier de Jolimont-Lobbes
Haine-Saint-Paul, Hainaut, Belgium, 7100
Universitair Ziekenhuis Gent
Gent, Oost-Vlaanderen, Belgium, 9000
Sponsors and Collaborators
Achillion Pharmaceuticals
Investigators
Study Director: Hetal Kocinsky, MD Achillion Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Achillion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01180790     History of Changes
Other Study ID Numbers: ACH625-003, 2010-022092-65
Study First Received: August 11, 2010
Results First Received: July 29, 2014
Last Updated: September 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Achillion Pharmaceuticals:
HCV
Hepatitis C Genotype 1

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferons
Ribavirin
Interferon-alpha
Peginterferon alfa-2a
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 16, 2014