Clinical trial NCT01672983: A Study to Evaluate ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Japanese Adults With Chronic Hepatitis C Virus Infection
Official title: A Phase 2 Study to Evaluate the Safety, Tolerability, Antiviral Activity, and Pharmacokinetics of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Japanese Adults With Chronic Hepatitis C Virus Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis C Infection
Keywords: Japanese
Hepatitis C
Genotype 2
Genotype 1b
paritaprevir
ombitasvir
ritonavir
VIEKIRAX Combination Tablets
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2012-08-27
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24)
timeFrame: 24 weeks after last dose of study drug
measure: Number of Participants With Adverse Events (AEs)
timeFrame: 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.
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12)
timeFrame: 12 weeks after last dose of study drug
measure: Percentage of Participants With End of Treatment (EOT) Response
timeFrame: 12 or 24 weeks after first dose of study drug
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: Takuma Matsuda, MS
role: STUDY_DIRECTOR
References:
citation: Chayama K, Notsumata K, Kurosaki M, Sato K, Rodrigues L Jr, Setze C, Badri P, Pilot-Matias T, Vilchez RA, Kumada H. Randomized trial of interferon- and ribavirin-free ombitasvir/paritaprevir/ritonavir in treatment-experienced hepatitis C virus-infected patients. Hepatology. 2015 May;61(5):1523-32. doi: 10.1002/hep.27705. Epub 2015 Mar 23.
citation: Schnell G, Tripathi R, Krishnan P, Beyer J, Reisch T, Irvin M, Dekhtyar T, Setze C, Rodrigues L Jr, Alves K, Burroughs M, Redman R, Chayama K, Kumada H, Collins C, Pilot-Matias T. Resistance characterization of hepatitis C virus genotype 2 from Japanese patients treated with ombitasvir and paritaprevir/ritonavir. J Med Virol. 2018 Jan;90(1):109-119. doi: 10.1002/jmv.24923. Epub 2017 Sep 22.