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

Hepatitis C Clinical Trial

Official title:

A Phase IIa, Randomized, Double-blind (Participant 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 Participants With Chronic Hepatitis C Virus Genotype 1

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01180790
• Other study ID #: ACH625-003
• Secondary ID: 2010-022092-65
• Status: Completed
• Phase: Phase 2
• Start date: September 2010
• Est. completion date: April 2013

Study information

• Verified date: August 2023
• Source: Alexion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 122
• Est. completion date: April 2013
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• ACH-0141625 (Sovaprevir)
200 mg oral capsule once daily
• ACH-0141625 (Sovaprevir)
400 mg oral capsule once daily
• ACH-0141625 (Sovaprevir)
800 mg oral capsule once daily
• Placebo
Powder in capsule once daily
• Pegylated Interferon alpha-2a
180 micrograms (ug) once a week by subcutaneous injection
• Ribavirin
400 mg or 600 mg (morning [AM]) and 600 mg (evening [PM]) capsules taken orally twice daily

Locations

Country	Name	City	State
Belgium	Clinical Trial Site	Edegem	Antwerp
Belgium	Clinical Trial Site	Gent	Oost-Vlaanderen
Belgium	Clinical Trial Site	Haine-Saint-Paul	Hainaut
United States	Clinical Trial Site	Arlington	Texas
United States	Clinical Trial Site	Bradenton	Florida
United States	Clinical Trial Site	Chicago	Illinois
United States	Clinical Trial Site	Las Vegas	Nevada
United States	Clinical Trial Site	Los Angeles	California
United States	Clinical Trial Site	Los Angeles	California
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Newport News	Virginia
United States	Clinical Trial Site	Norfolk	Virginia
United States	Clinical Trial Site	Orlando	Florida
United States	Clinical Trial Site	Overland Park	Kansas
United States	Clinical Trial Site	Philadelphia	Pennsylvania
United States	Clinical Trial Site	Saint Louis	Missouri
United States	Clinical Trial Site	San Antonio	Texas
United States	Clinical Trial Site	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Alexion	Achillion, a wholly owned subsidiary of Alexion

Countries where clinical trial is conducted

United States,  Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Segment 1: Safety	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.	4 weeks
Primary	Segment 1: Rapid Viral Response At Week 4 (RVR4)	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).	4 weeks
Primary	Segment 2: Safety	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.	12 weeks
Primary	Segment 2: Complete Early Virologic Response (cEVR)	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.	Week 12
Secondary	Segment 1: cEVR	For Segment 1, the percentage of participants in the virology population who achieved cEVR, defined as undetectable HCV RNA at Week 12.	12 weeks
Secondary	Segment 2: RVR4	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.	4 weeks
Secondary	Segment 1 And Segment 2: End Of Treatment Response	The percentage of virology population participants who were reported as undetectable HCV RNA at the completion of treatment.	Week 48 (Segment 1); Week 24 (Segment 2)
Secondary	Segment 1 And Segment 2: Sustained Virologic Response 12 Weeks (3 Months Post-dosing) (SVR12)	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.	3 months post-dosing
Secondary	Segment 1 And Segment 2: Sustained Virologic Response 24 Weeks (6 Months Post-dosing) (SVR24)	The percentage of virology population participants who achieved SVR, defined as HCV RNA less than the LOQ, 6 months post-dosing.	6 months post-dosing
Secondary	Segment 1 And Segment 2: HCV RNA Change From Baseline	The mean change from baseline in log10 HCV RNA level by visit for the virology population	Week 4
Secondary	Segment 1 And Segment 2: HCV RNA Change From Baseline	Change from baseline in log10 HCV RNA level by visit.	Week 12