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 (VOYAGE-1)

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Treatment-Naïve 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

This study will evaluate the efficacy and safety of glecaprevir/pibrentasvir (ABT-493/ABT-530) in non-cirrhotic chronic hepatitis C virus (HCV) genotype (GT)1 to GT6-infected Asian participants with or without human immunodeficiency virus (HIV) co-infection who are HCV treatment-naïve or treatment-experienced with interferon (IFN) with or without ribavirin (RBV), OR sofosbuvir with RBV with or without IFN.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus (HCV)
• Intervention / Treatment: Drug: Placebo; Drug: Glecaprevir/Pibrentasvir

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 546
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100015
    • Beijing Di Tan Hospital, Capital Medical University /ID# 156847
  • Beijing, China, 100034
    • 1st Hospital of Peking Uni /ID# 156845
  • Beijing, China, 100039
    • 302 Military Hospital Of China /ID# 156841
  • Beijing, China, 100050
    • Beijing Friendship Hospital /ID# 156840
  • Beijing, China, 100069
    • Beijing Youan Hosp, Cap Med Un /ID# 163430
  • Chongqing, China, 400038
    • 1st Affiliated Hosp 3rd Milita /ID# 156831
  • Dalian, China, 116031
    • Dalian Sixth Peoples Hospital /ID# 163433
  • Fuzhou, China, 350025
    • Mengchao Hepatobiliary Hospita /ID# 156902
  • Haikou, Hainan, China, 570311
    • Hainan General Hospital /ID# 156839
  • Jinan, Shandong, China, 250021
    • Jinan Infectious Diseases Hosp /ID# 156886
  • Nanjing, China, 210002
    • Chinese People's Liberation Army 81 Hospital /ID# 156862
  • Shenyang, China, 110004
    • Shengjing Hospital of China Medical University /ID# 156824
  • Tianjin, China, 300170
    • Tianjin Third Central Hospital /ID# 156816
  • Urumqi, China, 830054
    • 1st Aff Hosp Xinjiang Med Uni /ID# 156887
  • Wuhan, China, 430022
    • Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 156884
  • Wuhan, China, 430030
    • Tongji Hosp Tongji Med College /ID# 156885
  • Xi'an, China, 710038
    • Fourth Military Medical University Tangdu Hospital, PLA /ID# 156765
  • Xi'an, China, 710061
    • First Affiliated Hospital of Medical College of Xi'an Jiaotong University /ID# 163432
  • Zhengzhou, Henan, China, 450000
    • Henan Provincial Peoples Hosp /ID# 157197
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University Peoples Hospit /ID# 156846
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Guangzhou Eighth People's Hosp /ID# 156859
    • Guangzhou, Guangdong, China, 510080
      • Guangdong General Hospital /ID# 156822
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University /ID# 156860
    • Guangzhou, Guangdong, China, 510630
      • The Third Affiliated Hospital Of Sun Yat-Sen University /ID# 156900
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University /ID# 156901
  • Jiangsu
    • Nanjing, Jiangsu, China, 210003
      • The Second Hospital of Nanjing /ID# 156863
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province People's Hospital /ID# 156861
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hosp of Jilin Univ /ID# 156820
  • Liaoning
    • Shenyang, Liaoning, China, 110006
      • The Sixth People's Hospital of Shenyang /ID# 156849
  • Shanghai
    • Shanghai, Shanghai, China, 200003
      • Shanghai Changzheng Hospital /ID# 158072
    • Shanghai, Shanghai, China, 200025
      • Ruijin Hospital, Shanghai Jiaotong /ID# 157336
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital of Fudan University /ID# 156904
    • Shanghai, Shanghai, China, 201508
      • Shanghai Public Health Cli Ctr /ID# 156832
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital /ID# 156830
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital /ID# 163348
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center /ID# 163336
  • Busan Gwang Yeogsi
    • Busan, Busan Gwang Yeogsi, Korea, Republic of, 602-739
      • Pusan National University Hosp /ID# 163371
  • Gyeonggido
    • Seongnam, Gyeonggido, Korea, Republic of, 13620
      • Seoul National Univ Bundang ho /ID# 163367
  • Gyeongsangbugdo
    • Busan, Gyeongsangbugdo, Korea, Republic of, 47392
      • Inje University Busan Paik Hospital /ID# 163329
  • Gyeongsangnamdo
    • Yangsan-si,, Gyeongsangnamdo, Korea, Republic of, 50612
      • Pusan Nat Univ Yangsan Hosp /ID# 163334
  • Incheon Gwang Yeogsi
    • Jung-gu, Incheon Gwang Yeogsi, Korea, Republic of, 22332
      • Inha University Hospital /ID# 163320
  • Seoul Teugbyeolsi
    • Seodaemun-gu, Seoul Teugbyeolsi, Korea, Republic of, 03722
      • Yonsei University Health System, Severance Hospital /ID# 163339
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06351
      • Samsung Medical Center /ID# 163364
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06591
      • Cath Univ Seoul St Mary's Hosp /ID# 163341
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 08308
      • Korea Universtiy Guro Hospital /ID# 163380
• Singapore
  • Singapore, Singapore, 119228
    • National University Hospital ( /ID# 163272
  • Singapore, Singapore, 169608
    • Singapore General Hospital /ID# 163271
  • Singapore, Singapore, 529889
    • Changi General Hospital /ID# 163270

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glecaprevir/Pibrentasvir; Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 or 16 weeks during the double-blind (DB) treatment period. Participants received treatment for 8 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks.	Drug: Glecaprevir/Pibrentasvir; Coformulated tablet for oral administration; Other Names: ABT-493/ABT-530; MAVYRET™
Experimental: Placebo / Glecaprevir/Pibrentasvir; Participants received placebo to glecaprevir/pibrentasvir for 8 or 16 weeks during the DB treatment period followed by glecaprevir/pibrentasvir (300 mg/120 mg) once daily for 8 or 16 weeks during the open-label (OL) treatment period. In each period participants received treatment for 8 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks.	Drug: Placebo; Matching placebo tablet for oral administration; Drug: Glecaprevir/Pibrentasvir; Coformulated tablet for oral administration; Other Names: ABT-493/ABT-530; MAVYRET™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of HCV GT1 - GT6-Infected Participants in Arm A Who Achieved Sustained Virologic Response 12 Weeks Post Treatment (SVR12)	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.	12 weeks after the last actual dose of study drug, Week 20 or Week 28 depending on the treatment regimen.
Percentage of HCV GT1-Infected Participants in Arm A Who Achieved SVR12	SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last dose of study drug.	12 weeks after last actual dose of study drug, Week 20 or Week 28 depending on the treatment regimen
Percentage of HCV GT2-Infected Participants in Arm A Who Achieved SVR12	SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last actual dose of study drug.	12 weeks after the last dose of study drug, Week 20 or Week 28 depending on the treatment regimen.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants in Arm A With On-treatment Virologic Failure	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.	8 or 16 weeks depending on the treatment regimen
Percentage of Participants in Arm A With Post-treatment Relapse	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.	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).
Percentage of HCV/HIV Co-infected Participants in Arm A Who Achieved SVR12	SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last dose of study drug.	12 weeks after the last actual dose of study drug, Week 20 or 28 depending on the treatment regimen

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2017
• Primary Completion (Actual): October 18, 2018
• Study Completion (Actual): February 15, 2019

Study Registration Dates

• First Submitted: July 17, 2017
• First Submitted That Met QC Criteria: July 17, 2017
• First Posted (Actual): July 19, 2017

Study Record Updates

• Last Update Posted (Actual): December 23, 2019
• Last Update Submitted That Met QC Criteria: December 5, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: interferon; Human Immunodeficiency Virus; Asian; non-cirrhotic; Chronic Hepatitis C Virus (HCV); Genotype 1 to 6; co-infection; Treatment-naïve; Treatment-experienced
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Slow Virus Diseases; HIV Infections; Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Hepatitis C, Chronic; Coinfection
• Other Study ID Numbers: M15-592

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No