Clinical trial NCT02707952: A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Japanese Adults With Chronic Hepatitis C Virus Infection
Official title: A Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Japanese Adults With Chronic Hepatitis C Virus Infection (CERTAIN-1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Hepatitis C Virus
Hepatitis C Virus
Keywords: Compensated cirrhosis
Non-cirrhotic
Renal impairment
Hepatitis C virus (HCV)
Hepatitis C
Chronic Hepatitis C
Hepatitis C Genotype 1
Hepatitis C Genotype 2
Hepatitis C Genotype 3
Hepatitis C Genotype 4
Hepatitis C Genotype 5
Hepatitis C Genotype 6
DAA-experienced
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-03-14
Enrollment: 295
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this phase 3, multicenter study is to evaluate the efficacy and safety of ABT-493/ABT-530 in Japanese adults with chronic Hepatitis C Virus (HCV)-infected, HCV direct-acting antiviral agent (DAA) treatment-naïve, and DAA treatment-experienced Japanese adult subjects.

Detailed description: The study consisted of two sub-studies that enrolled in parallel. Substudy 1 was randomized, open-label, and active-controlled, wherein HCV treatment-naïve or interferon (IFN)-experienced (i.e., DAA treatment-naïve), genotype (GT)1-infected participants without cirrhosis were enrolled. Substudy 2 was non-randomized, open label, and enrolled special populations of HCV-infected participants \[GT1- or GT2-infected subjects with compensated cirrhosis, HCV GT3-, 4-, 5- and 6-infected subjects (with compensated cirrhosis or without cirrhosis), HCV GT1- and GT2-infected subjects who had failed prior DAA treatments (with compensated cirrhosis or without cirrhosis), HCV GT1- or GT2-infected subjects with severe renal impairment (with compensated cirrhosis or without cirrhosis)\].

Eligibility criteria: Inclusion Criteria:

* Females were postmenopausal for at least 2 years; surgically sterile or had a vasectomized partner; or, if of childbearing potential and sexually active with a male partner, were currently using at least 1 effective method of birth control at the time of Screening and agreed to practice 1 effective method of birth control from Screening through 30 days after stopping study drug. Sexually active males were surgically sterile or, if sexually active with a female partner of childbearing potential, agreed to practice 1 effective form of birth control from Screening through 30 days after stopping study drug.
* Screening central laboratory result indicated HCV single genotype infection for the appropriate treatment arm, without co-infection of any other genotype.
* Chronic HCV infection is defined as one of the following:

  * Positive for anti-HCV antibody (Ab) and/or HCV RNA at least 6 months before Screening.
  * A liver biopsy consistent with chronic HCV infection.
* Agreed to voluntarily sign and date an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) prior to the initiation of any screening or study specific procedures.
* Participants who were able to understand and adhere to the study visit schedule and all other protocol requirements.
* Absence of hepatocellular carcinoma (HCC) as indicated by an ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI).

Exclusion Criteria:

* Females who were pregnant or planned to become pregnant, or breastfeeding or males whose partner was pregnant or planning to become pregnant during the study.
* Participants co-infected with hepatitis B virus or human immunodeficiency virus.
* Use of contraindicated medications or supplements within 2 weeks or 10 half-lives (if known), whichever was longer, prior to the first dose of any study drug.
* Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol in the opinion of the investigator.
* Any cause of liver disease other than chronic HCV infection.
* Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of decompensated liver disease.
* Consideration by the investigator, for any reason, that the participant is an unsuitable candidate to receive ABT-493/ABT-530.

Primary outcomes:
measure: Percentage of Participants in Arms A and B With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
timeFrame: 12 weeks after the last actual dose of study drug
Secondary outcomes:
measure: Percentage of Participants in Arm A With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
timeFrame: 12 weeks after the last actual dose of study drug
measure: Percentage of Participants for Each Sub-Population in Arms C and D With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
timeFrame: 12 weeks after the last actual dose of study drug
measure: Percentage of Participants With On-treatment Virologic Failure
timeFrame: Treatment Weeks 1, 2, 4, 8 (end of treatment for 8-week treatment arm), and 12 (end of treatment for 12-week treatment arm) or premature discontinuation from treatment
measure: Percentage of Participants With Post-Treatment Relapse
timeFrame: From the end of treatment through 12 weeks after the last dose of study drug
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: Chayama K, Suzuki F, Karino Y, Kawakami Y, Sato K, Atarashi T, Naganuma A, Watanabe T, Eguchi Y, Yoshiji H, Seike M, Takei Y, Kato K, Alves K, Burroughs M, Redman R, Pugatch DL, Pilot-Matias TJ, Krishnan P, Oberoi RK, Xie W, Kumada H. Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 1 hepatitis C virus infection with and without cirrhosis. J Gastroenterol. 2018 Apr;53(4):557-565. doi: 10.1007/s00535-017-1391-5. Epub 2017 Sep 25.
citation: Brown RS Jr, Collins MA, Strasser SI, Emmett A, Topp AS, Burroughs M, Ferreira R, Feld JJ. Efficacy and Safety of 8- or 12 Weeks of Glecaprevir/Pibrentasvir in Patients with Evidence of Portal Hypertension. Infect Dis Ther. 2022 Apr;11(2):913-924. doi: 10.1007/s40121-022-00599-8. Epub 2022 Feb 17.
citation: Naganuma A, Chayama K, Notsumata K, Gane E, Foster GR, Wyles D, Kwo P, Crown E, Bhagat A, Mensa FJ, Otani T, Larsen L, Burroughs M, Kumada H. Integrated analysis of 8-week glecaprevir/pibrentasvir in Japanese and overseas patients without cirrhosis and with hepatitis C virus genotype 1 or 2 infection. J Gastroenterol. 2019 Aug;54(8):752-761. doi: 10.1007/s00535-019-01569-7. Epub 2019 Mar 13.
citation: Krishnan P, Schnell G, Tripathi R, Beyer J, Reisch T, Dekhtyar T, Irvin M, Xie W, Fu B, Burroughs M, Redman R, Kumada H, Chayama K, Collins C, Pilot-Matias T. Integrated Resistance Analysis of CERTAIN-1 and CERTAIN-2 Studies in Hepatitis C Virus-Infected Patients Receiving Glecaprevir and Pibrentasvir in Japan. Antimicrob Agents Chemother. 2018 Jan 25;62(2):e02217-17. doi: 10.1128/AAC.02217-17. Print 2018 Feb.
citation: Yartel AK, Rein DB, Brown KA, Krauskopf K, Massoud OI, Jordan C, Kil N, Federman AD, Nerenz DR, Brady JE, Kruger DL, Smith BD. Hepatitis C virus testing for case identification in persons born during 1945-1965: Results from three randomized controlled trials. Hepatology. 2018 Feb;67(2):524-533. doi: 10.1002/hep.29548. Epub 2018 Jan 2.
citation: Toyoda H, Chayama K, Suzuki F, Sato K, Atarashi T, Watanabe T, Atsukawa M, Naganuma A, Notsumata K, Osaki Y, Nakamuta M, Takaguchi K, Saito S, Kato K, Pugatch D, Burroughs M, Redman R, Alves K, Pilot-Matias TJ, Oberoi RK, Fu B, Kumada H. Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 2 hepatitis C virus infection. Hepatology. 2018 Feb;67(2):505-513. doi: 10.1002/hep.29510. Epub 2017 Nov 24.