Clinical trial NCT03222583: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C Virus (HCV)
Keywords: Chronic Hepatitis C Virus (HCV)
Genotype 1 to 6
Asian
non-cirrhotic
Human Immunodeficiency Virus
co-infection
Treatment-naïve
Treatment-experienced
interferon
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2017-07-19
Enrollment: 546
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: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of HCV GT1 - GT6-Infected Participants in Arm A Who Achieved Sustained Virologic Response 12 Weeks Post Treatment (SVR12)
timeFrame: 12 weeks after the last actual dose of study drug, Week 20 or Week 28 depending on the treatment regimen.
measure: Percentage of HCV GT1-Infected Participants in Arm A Who Achieved SVR12
timeFrame: 12 weeks after last actual dose of study drug, Week 20 or Week 28 depending on the treatment regimen
measure: Percentage of HCV GT2-Infected Participants in Arm A Who Achieved SVR12
timeFrame: 12 weeks after the last dose of study drug, Week 20 or Week 28 depending on the treatment regimen.
Secondary outcomes:
measure: Percentage of Participants in Arm A With On-treatment Virologic Failure
timeFrame: 8 or 16 weeks depending on the treatment regimen
measure: Percentage of Participants in Arm A With Post-treatment Relapse
timeFrame: 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).
measure: Percentage of HCV/HIV Co-infected Participants in Arm A Who Achieved SVR12
timeFrame: 12 weeks after the last actual dose of study drug, Week 20 or 28 depending on the treatment regimen
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Peoples Hospit /ID# 156846
state: Beijing
city: Guangzhou
country: China
facility: Guangzhou Eighth People's Hosp /ID# 156859
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong General Hospital /ID# 156822
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University /ID# 156860
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital Of Sun Yat-Sen University /ID# 156900
state: Guangdong
city: Changsha
country: China
facility: Xiangya Hospital Central South University /ID# 156901
state: Hunan
city: Nanjing
country: China
facility: The Second Hospital of Nanjing /ID# 156863
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province People's Hospital /ID# 156861
state: Jiangsu
city: Changchun
country: China
facility: The First Hosp of Jilin Univ /ID# 156820
state: Jilin
city: Shenyang
country: China
facility: The Sixth People's Hospital of Shenyang /ID# 156849
state: Liaoning
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital /ID# 158072
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong /ID# 157336
state: Shanghai
city: Shanghai
country: China
facility: Huashan Hospital of Fudan University /ID# 156904
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Public Health Cli Ctr /ID# 156832
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital /ID# 156830
state: Sichuan
city: Beijing
country: China
facility: Beijing Di Tan Hospital, Capital Medical University /ID# 156847
city: Beijing
country: China
facility: 1st Hospital of Peking Uni /ID# 156845
city: Beijing
country: China
facility: 302 Military Hospital Of China /ID# 156841
city: Beijing
country: China
facility: Beijing Friendship Hospital /ID# 156840
city: Beijing
country: China
facility: Beijing Youan Hosp, Cap Med Un /ID# 163430
city: Chongqing
country: China
facility: 1st Affiliated Hosp 3rd Milita /ID# 156831
city: Dalian
country: China
facility: Dalian Sixth Peoples Hospital /ID# 163433
city: Fuzhou
country: China
facility: Mengchao Hepatobiliary Hospita /ID# 156902
city: Haikou, Hainan
country: China
facility: Hainan General Hospital /ID# 156839
city: Jinan, Shandong
country: China
facility: Jinan Infectious Diseases Hosp /ID# 156886
city: Nanjing
country: China
facility: Chinese People's Liberation Army 81 Hospital /ID# 156862
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University /ID# 156824
city: Tianjin
country: China
facility: Tianjin Third Central Hospital /ID# 156816
city: Urumqi
country: China
facility: 1st Aff Hosp Xinjiang Med Uni /ID# 156887
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 156884
city: Wuhan
country: China
facility: Tongji Hosp Tongji Med College /ID# 156885
city: Xi'an
country: China
facility: Fourth Military Medical University Tangdu Hospital, PLA /ID# 156765
city: Xi'an
country: China
facility: First Affiliated Hospital of Medical College of Xi'an Jiaotong University /ID# 163432
city: Zhengzhou, Henan
country: China
facility: Henan Provincial Peoples Hosp /ID# 157197
city: Busan
country: Korea, Republic of
facility: Pusan National University Hosp /ID# 163371
state: Busan Gwang Yeogsi
city: Seongnam
country: Korea, Republic of
facility: Seoul National Univ Bundang ho /ID# 163367
state: Gyeonggido
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital /ID# 163329
state: Gyeongsangbugdo
city: Yangsan-si,
country: Korea, Republic of
facility: Pusan Nat Univ Yangsan Hosp /ID# 163334
state: Gyeongsangnamdo
city: Jung-gu
country: Korea, Republic of
facility: Inha University Hospital /ID# 163320
state: Incheon Gwang Yeogsi
city: Seodaemun-gu
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital /ID# 163339
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center /ID# 163364
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Cath Univ Seoul St Mary's Hosp /ID# 163341
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Korea Universtiy Guro Hospital /ID# 163380
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 163348
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 163336
city: Singapore
country: Singapore
facility: National University Hospital ( /ID# 163272
city: Singapore
country: Singapore
facility: Singapore General Hospital /ID# 163271
city: Singapore
country: Singapore
facility: Changi General Hospital /ID# 163270
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.