Safety, Tolerability and Antiviral Activity of ACH-0141625 or Placebo in Combination With Peginterferon and Ribavirin in HCV Positive Subjects
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| ClinicalTrials.gov Identifier: NCT01180790 |
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Recruitment Status :
Completed
First Posted : August 12, 2010
Results First Posted : September 10, 2014
Last Update Posted : September 10, 2014
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Sponsor:
Alexion Pharmaceuticals
Information provided by (Responsible Party):
Alexion Pharmaceuticals
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Brief Summary:
Evaluate safety, tolerability and antiviral response of ACH-0141625 compared to Standard of Care in HCV positive subjects.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hepatitis C | Drug: ACH-0141625 (Sovaprevir) Drug: Placebo Drug: Pegylated Interferon alpha-2a Drug: Ribavirin | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 122 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, 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 |
| Study Start Date : | September 2010 |
| Actual Primary Completion Date : | March 2012 |
| Actual Study Completion Date : | April 2013 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Ribavirin
| Arm | Intervention/treatment |
|---|---|
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Experimental: Segment 1: 200 mg ACH-0141625
200 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a and ribavirin for 48 weeks
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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:
|
|
Experimental: Segment 1: 400 mg ACH-0141625
400 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus ribavirin for 48 weeks
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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:
|
|
Experimental: Segment 1: 800 mg ACH-0141625
800 mg ACH-0141625 for 28 days plus Peg-IFN alpha-2a plus ribavirin for 48 weeks
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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:
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Placebo Comparator: Segment 1: Placebo
Placebo for 28 days plus Peg-IFN alpha-2a plus ribavirin for 48 weeks
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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:
|
|
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
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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:
|
|
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:
|
|
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:
|
Primary Outcome Measures :
- Segment 1: Safety [ Time Frame: 4 weeks ]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 ]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 ]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 ]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 ]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 ]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) ]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 ]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 ]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 ]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 ]Change from baseline in log10 HCV RNA level by visit.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| 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)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01180790
Locations
Show 18 study locations
Sponsors and Collaborators
Alexion Pharmaceuticals
Investigators
| Study Director: | Hetal Kocinsky, MD | Alexion Pharmaceuticals |
| Responsible Party: | Alexion Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT01180790 |
| Other Study ID Numbers: |
ACH625-003 2010-022092-65 ( EudraCT Number ) |
| First Posted: | August 12, 2010 Key Record Dates |
| Results First Posted: | September 10, 2014 |
| Last Update Posted: | September 10, 2014 |
| Last Verified: | September 2014 |
Keywords provided by Alexion Pharmaceuticals:
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HCV Hepatitis C Genotype 1 |
Additional relevant MeSH terms:
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Hepatitis A Hepatitis C Hepatitis Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Flaviviridae Infections Interferons |
Ribavirin Interferon-alpha Interferon alpha-2 Peginterferon alfa-2a Antineoplastic Agents Antiviral Agents Anti-Infective Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Immunologic Factors Physiological Effects of Drugs |