A Study to Evaluate ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Japanese Adults With Chronic Hepatitis C Virus Infection

Phase 2

Completed

• Conditions: Chronic Hepatitis C Infection
• Interventions: Drug: ABT-450/ritonavir, ABT-267

• Registration Number: NCT01672983
• Lead Sponsor: AbbVie (prior sponsor, Abbott)

Brief Summary

This study evaluated the safety, tolerability, antiviral activity, and pharmacokinetics of ABT-450 (also known as paritaprevir) with ritonavir (ABT-450/r) and ABT-267 (also known as ombitasvir) in adult Japanese patients with chronic hepatitis C virus genotype 1b (HCV GT1b) or genotype 2 (HCV GT2) infection who were previous treated with pegylated interferon/ribavirin (pegIFN/RBV).

Detailed Description

This multicenter, randomized, open-label, parallel-arm, combination treatment study consisted of a Treatment and Post-treatment Phase, divided into 2 cohorts: 1) chronic HCV GT1b- infected, pegIFN/RBV treatment-exposed Japanese adults; and 2) HCV GT2-infected, pegIFN/RBV treatment-exposed Japanese adults. The Treatment Phase evaluated the antiviral activity, safety, and pharmacokinetics of a range of ABT-450/r and ABT-267 doses for 12 to 24 weeks. The Post-treatment Phase evaluated the evolution and persistence of viral resistance to ABT-267 and ABT-450.

Study Timeline

• Study Start: 2012-07
• Study First Submitted: 2012-07-27
• Study First Submitted QC: 2012-08-23
• Study First Posted: 2012-08-27
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Status Verified: 2015-10
• Results First Submitted: 2015-10-27
• Results First Submitted QC: 2015-10-27
• Results First Posted: 2015-11-26
• Last Update Submitted: 2018-04-30
• Last Update Posted: 2018-05-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

• Females must be practicing specific forms of birth control on study treatment, or be post-menopausal for more than 2 years or surgically sterile
• Chronic hepatitis C, genotype 1b (HCV-GT1b) or genotype 2 (HCV GT2) infection (HCV RNA level greater than 10,000 IU/mL at screening) previously treated with pegylated interferon/ribavirin (pegIFN/RBV).
• Subject's hepatitis C virus genotype is subgenotype 1b and subject was a null responder or partial responder, OR
• Subject's hepatitis C virus genotype is subgenotype 2 and subject was a null responder, partial responder, or relapser (Null responder: received at least 10 weeks of pegIFN/RBV for the treatment of HCV and failed to achieve a 2 log10 IU/mL reduction in HCV RNA at Week 12; Partial responders: received at least 20 weeks of pegIFN/RBV for the treatment of HCV and achieved ≥ 2 log10 IU/mL reduction in HCV RNA at Week 12, but failed to achieve HCV RNA undetectable (HCV RNA < lower limit of detection [< LLOD]) at the end of treatment; Relapsers: received at least 1 course of pegIFN/RBV for the treatment of HCV and was undetectable at the end of treatment, but HCV RNA was detectable within 24 weeks of treatment follow-up).

Exclusion Criteria

• Significant liver disease with any cause other than HCV as the primary cause
• Positive screen for drugs or alcohol.
• Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody.
• Use of contraindicated medications within 2 weeks of dosing
• Previous use of any investigational or commercially available anti-Hepatitis C virus agent other than pegIFN/RBV, including previous exposure to ABT-450 or ABT-267.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1	ABT-450/ritonavir, ABT-267	Participants with HCV GT1b received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 12 weeks.
Arm 4	ABT-450/ritonavir, ABT-267	Participants with HCV GT1b received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 24 weeks.
Arm 2	ABT-450/ritonavir, ABT-267	Participants with HCV GT1b received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 12 weeks.
Arm 3	ABT-450/ritonavir, ABT-267	Participants with HCV GT1b received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 24 weeks.
Arm 5	ABT-450/ritonavir, ABT-267	Participants with HCV GT2 received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 12 weeks.
Arm 6	ABT-450/ritonavir, ABT-267	Participants with HCV GT2 received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24)	24 weeks after last dose of study drug	The percentage of participants with SVR24 (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\] 24 weeks after the last dose of study drug). The LLOQ for the assay was 25 IU/mL.
Number of Participants With Adverse Events (AEs)	TEAEs: up to 16 weeks for the 12-week treatment groups and up to 28 weeks for the 24-week treatment groups; SAEs: up to 65 weeks for the 12-week treatment groups and up to 77 weeks for the 24-week treatment groups.	An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious adverse event (SAE) is an AE that results in death, is life-threatening, results in or prolongs hospitalization, results in congenital anomaly, persistent or significant disability/incapacity, spontaneous or elective abortion, or requires intervention to prevent a serious outcome. AEs were rated for severity as either Mild: transient and easily tolerated; Moderate: causes discomfort and interrupts usual activities; or Severe: causes considerable interference with usual activities, may be incapacitating or life-threatening. AEs related to study drug were assessed as being either probably or possibly related by the investigator. Treatment-emergent AEs (TEAEs) were collected from the first dose of study drug administration to 30 days after last dose; SAEs were collected from the time that informed consent was obtained to 30 days after last dose.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12)	12 weeks after last dose of study drug	The percentage of participants with SVR12 (plasma HCV RNA level \< LLOQ 12 weeks after the last dose of study drug). The LLOQ for the assay was 25 IU/mL.
Percentage of Participants With End of Treatment (EOT) Response	12 or 24 weeks after first dose of study drug	The percentage of participants with EOT response (plasma HCV RNA level \< LLOQ at week 12 for the 12-week duration arms and Week 24 for the 24-week duration arms12). The LLOQ for the assay was 25 IU/mL.