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
- Conditions
- Hepatitis C Virus (HCV)
- Interventions
- Drug: Glecaprevir/PibrentasvirDrug: Placebo
- Registration Number
- NCT03222583
- Lead Sponsor
- AbbVie
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 546
-
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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Glecaprevir/Pibrentasvir 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. Placebo / Glecaprevir/Pibrentasvir Placebo 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. Placebo / Glecaprevir/Pibrentasvir 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (48)
The Third Affiliated Hospital Of Sun Yat-Sen University /ID# 156900
🇨🇳Guangzhou, Guangdong, China
Xiangya Hospital Central South University /ID# 156901
🇨🇳Changsha, Hunan, China
Jiangsu Province People's Hospital /ID# 156861
🇨🇳Nanjing, Jiangsu, China
1st Aff Hosp Xinjiang Med Uni /ID# 156887
🇨🇳Urumqi, China
The First Hosp of Jilin Univ /ID# 156820
🇨🇳Changchun, Jilin, China
Nanfang Hospital of Southern Medical University /ID# 156860
🇨🇳Guangzhou, Guangdong, China
Peking University Peoples Hospit /ID# 156846
🇨🇳Beijing, Beijing, China
Guangzhou Eighth People's Hosp /ID# 156859
🇨🇳Guangzhou, Guangdong, China
The Second Hospital of Nanjing /ID# 156863
🇨🇳Nanjing, Jiangsu, China
Ruijin Hospital, Shanghai Jiaotong /ID# 157336
🇨🇳Shanghai, Shanghai, China
The Sixth People's Hospital of Shenyang /ID# 156849
🇨🇳Shenyang, Liaoning, China
West China Hospital /ID# 156830
🇨🇳Chengdu, Sichuan, China
1st Hospital of Peking Uni /ID# 156845
🇨🇳Beijing, China
Hainan General Hospital /ID# 156839
🇨🇳Haikou, Hainan, China
Beijing Youan Hosp, Cap Med Un /ID# 163430
🇨🇳Beijing, China
Jinan Infectious Diseases Hosp /ID# 156886
🇨🇳Jinan, Shandong, China
Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 156884
🇨🇳Wuhan, China
Tongji Hosp Tongji Med College /ID# 156885
🇨🇳Wuhan, China
Fourth Military Medical University Tangdu Hospital, PLA /ID# 156765
🇨🇳Xi'an, China
First Affiliated Hospital of Medical College of Xi'an Jiaotong University /ID# 163432
🇨🇳Xi'an, China
Pusan Nat Univ Yangsan Hosp /ID# 163334
🇰🇷Yangsan-si,, Gyeongsangnamdo, Korea, Republic of
Henan Provincial Peoples Hosp /ID# 157197
🇨🇳Zhengzhou, Henan, China
Inje University Busan Paik Hospital /ID# 163329
🇰🇷Busan, Gyeongsangbugdo, Korea, Republic of
Inha University Hospital /ID# 163320
🇰🇷Jung-gu, Incheon Gwang Yeogsi, Korea, Republic of
Cath Univ Seoul St Mary's Hosp /ID# 163341
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Korea Universtiy Guro Hospital /ID# 163380
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Seoul National University Hospital /ID# 163348
🇰🇷Seoul, Korea, Republic of
Seoul National Univ Bundang ho /ID# 163367
🇰🇷Seongnam, Gyeonggido, Korea, Republic of
Asan Medical Center /ID# 163336
🇰🇷Seoul, Korea, Republic of
Guangdong General Hospital /ID# 156822
🇨🇳Guangzhou, Guangdong, China
Beijing Friendship Hospital /ID# 156840
🇨🇳Beijing, China
Shanghai Changzheng Hospital /ID# 158072
🇨🇳Shanghai, Shanghai, China
302 Military Hospital Of China /ID# 156841
🇨🇳Beijing, China
Huashan Hospital of Fudan University /ID# 156904
🇨🇳Shanghai, Shanghai, China
Beijing Di Tan Hospital, Capital Medical University /ID# 156847
🇨🇳Beijing, China
Shanghai Public Health Cli Ctr /ID# 156832
🇨🇳Shanghai, Shanghai, China
Dalian Sixth Peoples Hospital /ID# 163433
🇨🇳Dalian, China
Chinese People's Liberation Army 81 Hospital /ID# 156862
🇨🇳Nanjing, China
Mengchao Hepatobiliary Hospita /ID# 156902
🇨🇳Fuzhou, China
1st Affiliated Hosp 3rd Milita /ID# 156831
🇨🇳Chongqing, China
Shengjing Hospital of China Medical University /ID# 156824
🇨🇳Shenyang, China
Tianjin Third Central Hospital /ID# 156816
🇨🇳Tianjin, China
Pusan National University Hosp /ID# 163371
🇰🇷Busan, Busan Gwang Yeogsi, Korea, Republic of
Yonsei University Health System, Severance Hospital /ID# 163339
🇰🇷Seodaemun-gu, Seoul Teugbyeolsi, Korea, Republic of
Samsung Medical Center /ID# 163364
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Changi General Hospital /ID# 163270
🇸🇬Singapore, Singapore
Singapore General Hospital /ID# 163271
🇸🇬Singapore, Singapore
National University Hospital ( /ID# 163272
🇸🇬Singapore, Singapore