Clinical trial NCT02723084: A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Japanese Adults With Genotype 2 Chronic Hepatitis C Virus Infection
Official title: A Randomized, Open-Label, Active Comparator, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Japanese Adults With Genotype 2 Chronic Hepatitis C Virus Infection (CERTAIN-2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Hepatitis C Virus
Hepatitis C Virus
Keywords: Hepatitis C Virus
Non-cirrhotic
Hepatitis C Genotype 2
Chronic Hepatitis C Virus
Hepatitis C
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2016-03-30
Enrollment: 136
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 study is to evaluate the efficacy and safety of ABT-493/ABT-530 in comparison to sofosbuvir plus ribavirin for 12 weeks in Hepatitis C Virus (HCV) Genotype 2 (GT2) infected participants.

Detailed description: This was a randomized, open-label, active-control, multicenter study to evaluate efficacy, safety, and pharmacokinetics of ABT-493/ABT-530 in chronic HCV GT2-infected direct-acting antiviral agent (DAA) treatment-naïve Japanese adult participants without cirrhosis. The participants were randomized in a 2:1 ratio to ABT-493/ABT-530 for 8 weeks (Arm A) and sofosbuvir plus ribavirin for 12 weeks (Arm B).

Eligibility criteria: Inclusion Criteria:

* Females were postmenopausal for at least 2 years prior to screening; 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 indicating HCV GT-2 infection without co-infection of any other genotype.
* Participant has positive anti-HCV antibody (Ab) and plasma HCV RNA viral load greater than or equal to 1000 IU/mL at Screening Visit.
* Chronic HCV infection defined as one of the following:

  * Positive for anti-HCV Ab and/or HCV RNA at least 6 months before Screening; or
  * A liver biopsy consistent with chronic HCV infection.
* Participant must be HCV treatment-naïve (i.e., patient has not received a single dose of any approved or investigational DAA) and non-cirrhotic. Prior HCV treatment using IFNs with or without ribavirin is acceptable. Previous HCV Interferon (IFN) based treatment must have been completed greater than or equal to 2 months prior to screening.

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.
* 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.
* Positive test result at Screening for hepatitis B surface antigen (HBsAg) or anti human immunodeficiency virus antibody (HIV Ab).
* Requirement for and inability to safely discontinue contraindicated medications or supplements at least 2 weeks or 10 half-lives (whichever is longer) prior to the first dose of any study drug.
* Clinically significant abnormalities, other than HCV-infection, based upon the results of a medical history, physical examination, vital signs, laboratory profile, and a 12-lead electrocardiogram (ECG) that make the participant an unsuitable candidate for this study in the opinion of the investigator, including, but not limited to:

  * Uncontrolled diabetes as defined by a glycated hemoglobin (hemoglobin A1C) level \> 8.5% at the Screening Visit.
  * Active or suspected malignancy or history of malignancy (other than basal cell skin cancer or cervical carcinoma in situ) in the past 5 years, or any history of hepatocellular carcinoma (HCC).
  * Uncontrolled cardiac, respiratory, gastrointestinal, hematologic, neurologic, psychiatric, or other medical disease or disorder, which is unrelated to the existing HCV infection.
* Any cause of liver disease other than chronic HCV-infection, including but not limited to the following:

  * Hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's disease, autoimmune hepatitis, alcoholic liver disease, or steatohepatitis considered to be the primary cause of the liver disease rather than concomitant/incidental with HCV infection.

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Non-inferiority of Arm A to Arm B
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 With With On-treatment Virologic Failure
timeFrame: Treatment Weeks 1, 2, 4, 8 (end of treatment for arm A), and 12 (end of treatment for arm B) 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., MD
role: STUDY_DIRECTOR
References:
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.
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.