A Study to Evaluate the Efficacy and Safety of Glecaprevir/Pibrentasvir (ABT-493/ABT-530) in Treatment-Naive and Treatment-Experienced, Non-Cirrhotic Asian Adults With Chronic Hepatitis C Virus Genotype (GT) 1 to GT6 Infection With or Without Human Immunodeficiency Virus Co-Infection

Randomization was stratified by geographic region (China, South Korea, Singapore), genotype (GT1, GT2, combined GT3 - 6), and HCV/HIV co-infection status (co-infected, not co-infected). In China, eligible participants were randomized to Arm A or Arm B (defined below) in the following ratios: 2:1 for GT1, 2:1 for GT2, and 2:1 for combined GT3-6. In South Korea and Singapore, eligible participants were randomized to Arm A or Arm B in the following ratios: 2:1 for GT1 and 2:1 for GT2.

All Primary and Secondary Outcome Measures were pre-specified to be analyzed only in Arm A.

• Placebo (Drug): Matching placebo tablet for oral administration
• Glecaprevir/Pibrentasvir (Drug), also known as ABT-493/ABT-530, MAVYRET™: Coformulated tablet for oral administration

Primary outcomes

• Percentage of HCV GT1 - GT6-Infected Participants in Arm A Who Achieved Sustained Virologic Response 12 Weeks Post Treatment (SVR12) [12 weeks after the last actual dose of study drug, Week 20 or Week 28 depending on the treatment regimen.]: Sustained virologic response 12 weeks post-treatment (SVR12) was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; less than 15 IU/mL) 12 weeks after the last dose of study drug.
• Percentage of HCV GT1-Infected Participants in Arm A Who Achieved SVR12 [12 weeks after last actual dose of study drug, Week 20 or Week 28 depending on the treatment regimen]: SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last dose of study drug.
• Percentage of HCV GT2-Infected Participants in Arm A Who Achieved SVR12 [12 weeks after the last dose of study drug, Week 20 or Week 28 depending on the treatment regimen.]: SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last actual dose of study drug.

Secondary outcomes

• Percentage of Participants in Arm A With On-treatment Virologic Failure [8 or 16 weeks depending on the treatment regimen]: On-treatment virologic failure was defined as meeting one of the following: * confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements > 1 log₁₀ IU/mL above nadir) at any time point during the treatment period; or * confirmed HCV RNA greater than or equal to 100 IU/mL after HCV RNA < 15 IU/mL during the treatment period, or * HCV RNA ≥ 15 IU/mL at end of treatment with at least 6 weeks of treatment.
• Percentage of Participants in Arm A With Post-treatment Relapse [From the end of treatment (Weeks 8 or 16) through 12 weeks after the last dose of study drug (Weeks 20 or 28 depending on the treatment regimen).]: Post-treatment relapse was defined as confirmed HCV RNA greater than or equal to 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels < 15 IU/mL at the end of treatment, excluding re-infection.
• Percentage of HCV/HIV Co-infected Participants in Arm A Who Achieved SVR12 [12 weeks after the last actual dose of study drug, Week 20 or 28 depending on the treatment regimen]: SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last dose of study drug.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Must be of Asian descent
* Screening laboratory result indicating hepatitis C virus (HCV) genotype (GT) 1, 2, 3, 4, 5 or 6 infection.
* Positive anti-HCV antibody (Ab) and HCV ribonucleic acid (RNA) viral load ≥ 1000 IU/ mL at Screening Visit.
* Chronic HCV infection defined as one of the following:

  * Positive for anti-HCV Ab or HCV RNA at least 6 months before Screening; or
  * A liver biopsy consistent with chronic HCV infection
* HCV treatment-naïve to any approved or investigational HCV treatment or treatment-experienced with interferon (IFN) (alpha, beta or pegylated interferon\[pegIFN\] with or without ribavirin, OR sofosbuvir with RBV with or without IFN. Previous treatment must have been completed ≥ 8 weeks prior to screening.
* Participant must be documented as non-cirrhotic.
* Participants enrolled with human immunodeficiency virus (HIV)-1 and HCV co-infection must also meet the following criteria:

  * Positive test result for human immunodeficiency virus antibody (HIV Ab) at Screening
  * Naïve to treatment with any antiretroviral therapy (ART) with a cluster of differentiation (CD)4+ count greater than or equal to 500 cells/mm³ (or CD4+ percent ≥ 29%)
  * On a stable, qualifying HIV-1 ART regimen with CD4+ count ≥ 200 cells/mm³ (or CD4+ % ≥ 14%) at Screening and plasma HIV-1 RNA below lower limit of quantification (LLOQ) by an approved plasma HIV-1 RNA quantitative assay at Screening and at least once during the 12 months prior to Screening.

Exclusion Criteria:

* Positive test result for Hepatitis B surface antigen (HbsAg) or positive test result for hepatitis B virus (HBV) deoxyribonucleic acid (DNA) if HBsAg is negative.
* Any cause of liver disease other than chronic HCV-infection.
* HCV genotype performed during screening indicating co-infection with more than one HCV genotype
* Clinically significant abnormalities, other than HCV infection or HCV/HIV co-infection
* Chronic human immunodeficiency virus, type 2 (HIV-2) infection

Additional Exclusion Criteria for participants with HCV/HIV Co-Infection:

* For participants on stable ART, taking anti-retroviral agent(s) other than those permitted
* Treatment for an acquired immunodeficiency syndrome (AIDS)-associated opportunistic infection within 12 months of Screening or prophylaxis for an AIDS-associated opportunistic infection within 6 months of screening
* Diagnosis of any clinical AIDS-defining event within 12 months prior to Screening.

Participant flow

Outcome results

• Percentage of HCV GT1 - GT6-Infected Participants in Arm A Who Achieved Sustained Virologic Response 12 Weeks Post Treatment (SVR12) (Primary), Number, percentage of participants: Arm A: Glecaprevir/Pibrentasvir 97.2
• Percentage of HCV GT1-Infected Participants in Arm A Who Achieved SVR12 (Primary), Number, percentage of participants: Arm A: Glecaprevir/Pibrentasvir 99.4
• Percentage of HCV GT2-Infected Participants in Arm A Who Achieved SVR12 (Primary), Number, percentage of participants: Arm A: Glecaprevir/Pibrentasvir 97.8
• Percentage of Participants in Arm A With On-treatment Virologic Failure (Secondary), Number, percentage of participants: Arm A: Glecaprevir/Pibrentasvir 0.6 (0.2 to 2.0)
• Percentage of Participants in Arm A With Post-treatment Relapse (Secondary), Number, percentage of participants: Arm A: Glecaprevir/Pibrentasvir 1.7 (0.8 to 3.6)
• Percentage of HCV/HIV Co-infected Participants in Arm A Who Achieved SVR12 (Secondary)

Adverse events

Time frame: Double-blind Treatment Period: From initiation of study drug through 30 days after last dose and prior to Day 1 of the open-label period, if applicable; up to 12 or 20 weeks depending on the treatment regimen. Open-label Treatment Period (Arm B only): From the first dose of study drug in the OL period up to 30 days after the last dose of OL study drug; up to 12 or 20 weeks depending on the treatment regimen.

Serious adverse events by term

Other adverse events by term

• Results publication: Wei L, Wang G, Alami NN, Xie W, Heo J, Xie Q, Zhang M, Kim YJ, Lim SG, Fredrick LM, Lu W, Liu W, Kalluri HV, Krishnan P, Tripathi R, Mobashery N, Burroughs M, Asatryan A, Jia J, Hou J. Glecaprevir-pibrentasvir to treat chronic hepatitis C virus infection in Asia: two multicentre, phase 3 studies- a randomised, double-blind study (VOYAGE-1) and an open-label, single-arm study (VOYAGE-2). Lancet Gastroenterol Hepatol. 2020 Sep;5(9):839-849. doi: 10.1016/S2468-1253(20)30086-8. Epub 2020 Jul 16. PMID 32682494

• Statistical Analysis Plan (PDF, 2018-01-15)
• Study Protocol (PDF, 2017-04-03)

• AbbVie Inc., Study director, AbbVie