VOYAGE-1: 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

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03222583
• Collaborator: (none)
• Enrollment: 546
• Locations: 48
• Arms: 2
• Actual Duration (Months): 16.4
• Patients Per Site: 11.4
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Virus (HCV)	Drug: Placebo; Drug: Glecaprevir/Pibrentasvir	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 546 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Oct 4, 2017
• Actual Primary Completion Date: Oct 18, 2018
• Actual Study Completion Date: Feb 15, 2019

Arms and Interventions

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™

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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

1. 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.

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking University Peoples Hospit /ID# 156846	Beijing	Beijing	China	100044
2	Guangzhou Eighth People's Hosp /ID# 156859	Guangzhou	Guangdong	China	510060
3	Guangdong General Hospital /ID# 156822	Guangzhou	Guangdong	China	510080
4	Nanfang Hospital of Southern Medical University /ID# 156860	Guangzhou	Guangdong	China	510515
5	The Third Affiliated Hospital Of Sun Yat-Sen University /ID# 156900	Guangzhou	Guangdong	China	510630
6	Xiangya Hospital Central South University /ID# 156901	Changsha	Hunan	China	410008
7	The Second Hospital of Nanjing /ID# 156863	Nanjing	Jiangsu	China	210003
8	Jiangsu Province People's Hospital /ID# 156861	Nanjing	Jiangsu	China	210029
9	The First Hosp of Jilin Univ /ID# 156820	Changchun	Jilin	China	130021
10	The Sixth People's Hospital of Shenyang /ID# 156849	Shenyang	Liaoning	China	110006
11	Shanghai Changzheng Hospital /ID# 158072	Shanghai	Shanghai	China	200003
12	Ruijin Hospital, Shanghai Jiaotong /ID# 157336	Shanghai	Shanghai	China	200025
13	Huashan Hospital of Fudan University /ID# 156904	Shanghai	Shanghai	China	200040
14	Shanghai Public Health Cli Ctr /ID# 156832	Shanghai	Shanghai	China	201508
15	West China Hospital /ID# 156830	Chengdu	Sichuan	China	610041
16	Beijing Di Tan Hospital, Capital Medical University /ID# 156847	Beijing		China	100015
17	1st Hospital of Peking Uni /ID# 156845	Beijing		China	100034
18	302 Military Hospital Of China /ID# 156841	Beijing		China	100039
19	Beijing Friendship Hospital /ID# 156840	Beijing		China	100050
20	Beijing Youan Hosp, Cap Med Un /ID# 163430	Beijing		China	100069
21	1st Affiliated Hosp 3rd Milita /ID# 156831	Chongqing		China	400038
22	Dalian Sixth Peoples Hospital /ID# 163433	Dalian		China	116031
23	Mengchao Hepatobiliary Hospita /ID# 156902	Fuzhou		China	350025
24	Hainan General Hospital /ID# 156839	Haikou, Hainan		China	570311
25	Jinan Infectious Diseases Hosp /ID# 156886	Jinan, Shandong		China	250021
26	Chinese People's Liberation Army 81 Hospital /ID# 156862	Nanjing		China	210002
27	Shengjing Hospital of China Medical University /ID# 156824	Shenyang		China	110004
28	Tianjin Third Central Hospital /ID# 156816	Tianjin		China	300170
29	1st Aff Hosp Xinjiang Med Uni /ID# 156887	Urumqi		China	830054
30	Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 156884	Wuhan		China	430022
31	Tongji Hosp Tongji Med College /ID# 156885	Wuhan		China	430030
32	Fourth Military Medical University Tangdu Hospital, PLA /ID# 156765	Xi'an		China	710038
33	First Affiliated Hospital of Medical College of Xi'an Jiaotong University /ID# 163432	Xi'an		China	710061
34	Henan Provincial Peoples Hosp /ID# 157197	Zhengzhou, Henan		China	450000
35	Pusan National University Hosp /ID# 163371	Busan	Busan Gwang Yeogsi	Korea, Republic of	602-739
36	Seoul National Univ Bundang ho /ID# 163367	Seongnam	Gyeonggido	Korea, Republic of	13620
37	Inje University Busan Paik Hospital /ID# 163329	Busan	Gyeongsangbugdo	Korea, Republic of	47392
38	Pusan Nat Univ Yangsan Hosp /ID# 163334	Yangsan-si,	Gyeongsangnamdo	Korea, Republic of	50612
39	Inha University Hospital /ID# 163320	Jung-gu	Incheon Gwang Yeogsi	Korea, Republic of	22332
40	Yonsei University Health System, Severance Hospital /ID# 163339	Seodaemun-gu	Seoul Teugbyeolsi	Korea, Republic of	03722
41	Samsung Medical Center /ID# 163364	Seoul	Seoul Teugbyeolsi	Korea, Republic of	06351
42	Cath Univ Seoul St Mary's Hosp /ID# 163341	Seoul	Seoul Teugbyeolsi	Korea, Republic of	06591
43	Korea Universtiy Guro Hospital /ID# 163380	Seoul	Seoul Teugbyeolsi	Korea, Republic of	08308
44	Seoul National University Hospital /ID# 163348	Seoul		Korea, Republic of	03080
45	Asan Medical Center /ID# 163336	Seoul		Korea, Republic of	05505
46	National University Hospital ( /ID# 163272	Singapore		Singapore	119228
47	Singapore General Hospital /ID# 163271	Singapore		Singapore	169608
48	Changi General Hospital /ID# 163270	Singapore		Singapore	529889

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc., AbbVie

Study Documents (Full-Text)

• Statistical Analysis Plan - Jan 15, 2018
• Study Protocol - Apr 3, 2017

More Information

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT03222583
• Other Study ID Numbers: M15-592
• First Posted: Jul 19, 2017
• Last Update Posted: Dec 23, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Keywords provided by AbbVie: Chronic Hepatitis C Virus (HCV); Genotype 1 to 6; Asian; non-cirrhotic; Human Immunodeficiency Virus; co-infection; Treatment-naïve; Treatment-experienced; interferon
• Additional relevant MeSH terms: Infections; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Acquired Immunodeficiency Syndrome; HIV Infections; Coinfection; Hepatitis; Hepatitis, Chronic; Immunologic Deficiency Syndromes

Study Results

Participant Flow

Recruitment Details	This study was conducted at 47 sites in China, South Korea, and Singapore. Eligible participants were non-cirrhotic chronic hepatitis C (HCV) genotype (GT)1-6-infected adults with or without HIV co-infection who were HCV treatment-naïve or treatment-experienced with regimens containing interferon (IFN), pegylated IFN, ribavirin, and/or sofosbuvir.
Pre-assignment Detail	Randomization was stratified by geographic region, genotype (GT1, GT2, combined GT3 - 6), and HCV/HIV co-infection status (co-infected, not co-infected). Participants were randomized to Arm A or Arm B in the following ratios: China: 2:1 for GT1, 2:1 for GT2, and 2:1 for combined GT3 - 6; South Korea and Singapore: 2:1 for GT1 and 2:1 for GT2.

Arm/Group Title	Arm A: Glecaprevir/Pibrentasvir	Arm B: Placebo / Glecaprevir/Pibrentasvir
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	363	183
Received Double-blind Treatment	362	183
Completed Double-blind Period	360	183
Entered Open-label Period	0	182
Completed Open-label Period	0	181
COMPLETED	358	177
NOT COMPLETED	5	6

Baseline Characteristics

Arm/Group Title	Arm A: Glecaprevir/Pibrentasvir	Arm B: Placebo / Glecaprevir/Pibrentasvir	Total
Arm/Group Description	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 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.	Total of all reporting groups
Overall Participants	362	183	545
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.68 (12.96)	49.18 (13.55)	48.85 (13.15)
Sex: Female, Male (Count of Participants)
Female	180 49.7%	97 53%	277 50.8%
Male	182 50.3%	86 47%	268 49.2%
Race/Ethnicity, Customized (Count of Participants)
Asian	362 100%	183 100%	545 100%
Region of Enrollment (Count of Participants)
South Korea	82 22.7%	42 23%	124 22.8%
Singapore	21 5.8%	11 6%	32 5.9%
China	259 71.5%	130 71%	389 71.4%
HCV Genotype (Count of Participants)
Genotype 1	179 49.4%	89 48.6%	268 49.2%
Genotype 2	139 38.4%	71 38.8%	210 38.5%
Genotype 3	26 7.2%	10 5.5%	36 6.6%
Genotype 4	0 0%	1 0.5%	1 0.2%
Genotype 5	0 0%	0 0%	0 0%
Genotype 6	18 5%	12 6.6%	30 5.5%
Prior HCV Treatment History (Count of Participants)
Treatment-naive	281 77.6%	155 84.7%	436 80%
Treatment-experienced	81 22.4%	28 15.3%	109 20%
Human Immunodeficiency Virus (HIV) Co-infection Status (Count of Participants)
Hepatitis C infection only	362 100%	183 100%	545 100%
HCV / HIV co-infection	0 0%	0 0%	0 0%
HCV Ribonucleic Acid (RNA) Level (log₁₀ IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log₁₀ IU/mL]	6.37 (0.72)	6.26 (0.79)	6.33 (0.74)

Outcome Measures

1. Primary Outcome

Title	Percentage of HCV GT1 - GT6-Infected Participants in Arm A Who Achieved Sustained Virologic Response 12 Weeks Post Treatment (SVR12)
Description	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.
Time Frame	12 weeks after the last actual dose of study drug, Week 20 or Week 28 depending on the treatment regimen.

Outcome Measure Data

Analysis Population Description

This endpoint was pre-specified to be analyzed in participants randomized to Arm A who received at least 1 dose of study drug during the DB Treatment Period. Backward imputation, where applicable, was used to impute missing data. Participants with missing data after backward imputation were counted as non-responders.

Arm/Group Title	Arm A: Glecaprevir/Pibrentasvir
Arm/Group Description	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.
Measure Participants	362
Number [percentage of participants]	97.2 26.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Glecaprevir/Pibrentasvir
	Comments	In order to control the Type I error rate, a fixed sequence testing procedure was used for the 3 ranked primary efficacy endpoints. Only if success had been demonstrated for the first primary endpoint was testing to proceed to the second primary endpoint. Similarly, only if success had been demonstrated for the second primary endpoint was testing to proceed to the third primary endpoint.
	Type of Statistical Test	Non-Inferiority
	Comments	The percentage of participants in Arm A with SVR12 was non-inferior to the historical SVR12 rate of 96% if the lower confidence bound (LCB) of the 2-sided 95% confidence interval (CI) for the percentage was > 90%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants with SVR12
	Estimated Value	97.2
	Confidence Interval	(2-Sided) 95%; 95.5 to 98.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of HCV GT1-Infected Participants in Arm A Who Achieved SVR12
Description	SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last dose of study drug.
Time Frame	12 weeks after last actual dose of study drug, Week 20 or Week 28 depending on the treatment regimen

Outcome Measure Data

Analysis Population Description

This endpoint was pre-specified to be analyzed in GT1-infected participants randomized to Arm A who received at least one dose of study drug. Backward imputation, where applicable, was used to impute missing data. Participants with missing data after backward imputation were counted as non-responders.

Arm/Group Title	Arm A: Glecaprevir/Pibrentasvir
Arm/Group Description	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.
Measure Participants	179
Number [percentage of participants]	99.4 27.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Glecaprevir/Pibrentasvir
	Comments	In order to control the Type I error rate, a fixed sequence testing procedure was used for the 3 ranked primary efficacy endpoints. Only if success had been demonstrated for the first primary endpoint was testing to proceed to the second primary endpoint. Similarly, only if success had been demonstrated for the second primary endpoint was testing to proceed to the third primary endpoint.
	Type of Statistical Test	Non-Inferiority
	Comments	The percentage of GT1-infected participants in Arm A with SVR12 was non-inferior to the historical SVR12 rate of 97% if the LCB of the 2-sided 95% CI for the percentage was > 91%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants with SVR12
	Estimated Value	99.4
	Confidence Interval	(2-Sided) 95%; 98.3 to 100.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Percentage of HCV GT2-Infected Participants in Arm A Who Achieved SVR12
Description	SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last actual dose of study drug.
Time Frame	12 weeks after the last dose of study drug, Week 20 or Week 28 depending on the treatment regimen.

Outcome Measure Data

Analysis Population Description

This endpoint was pre-specified to be analyzed in genotype 2-infected participants randomized to Arm A who received at least one dose of study drug. Backward imputation, where applicable, was used to impute missing data. Participants with missing data after backward imputation were counted as non-responders.

Arm/Group Title	Arm A: Glecaprevir/Pibrentasvir
Arm/Group Description	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.
Measure Participants	139
Number [percentage of participants]	97.8 27%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Glecaprevir/Pibrentasvir
	Comments	In order to control the Type I error rate, a fixed sequence testing procedure was used for the 3 ranked primary efficacy endpoints. Only if success had been demonstrated for the first primary endpoint was testing to proceed to the second primary endpoint. Similarly, only if success had been demonstrated for the second primary endpoint was testing to proceed to the third primary endpoint.
	Type of Statistical Test	Non-Inferiority
	Comments	The percentage of GT2-infected participants in Arm A with SVR12 was non-inferior to the historical SVR12 rate of 95% if the LCB of the 2-sided 95% CI for the percentage was > 89%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants with SVR12
	Estimated Value	97.8
	Confidence Interval	(2-Sided) 95%; 95.4 to 100.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants in Arm A With On-treatment Virologic Failure
Description	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.
Time Frame	8 or 16 weeks depending on the treatment regimen

Outcome Measure Data

Analysis Population Description

This endpoint was pre-specified to be analyzed in all participants randomized to Arm A who received at least 1 dose of study drug during the DB Treatment Period.

Arm/Group Title	Arm A: Glecaprevir/Pibrentasvir
Arm/Group Description	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.
Measure Participants	362
Number (95% Confidence Interval) [percentage of participants]	0.6 0.2%

5. Secondary Outcome

Title	Percentage of Participants in Arm A With Post-treatment Relapse
Description	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.
Time Frame	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).

Outcome Measure Data

Analysis Population Description

This endpoint was pre-specified to be analyzed in all participants randomized to Arm A who received at least one dose of study drug, with HCV RNA < 15 IU/mL at the end of treatment, at least one post-treatment HCV RNA value, and who completed the assigned treatment.

Arm/Group Title	Arm A: Glecaprevir/Pibrentasvir
Arm/Group Description	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.
Measure Participants	359
Number (95% Confidence Interval) [percentage of participants]	1.7 0.5%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

No HCV-HIV co-infected participants were enrolled in the study

Arm/Group Title	Arm A: Glecaprevir/Pibrentasvir
Arm/Group Description	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.
Measure Participants	0

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.
Arm/Group Title	DB Period: Arm A - Glecaprevir/Pibrentasvir		DB Period: Arm B - Placebo		OL Period: Arm B - Glecaprevir/Pibrentasvir
Arm/Group Description	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.		Participants received placebo to glecaprevir/pibrentasvir for 8 or 16 weeks during the 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.		Participants randomized to receive placebo in the DB treatment period received glecaprevir/pibrentasvir (300 mg/120 mg) once daily for 8 or 16 weeks during the open-label (OL) treatment period. Participants received treatment for 8 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks.
All Cause Mortality
	DB Period: Arm A - Glecaprevir/Pibrentasvir		DB Period: Arm B - Placebo		OL Period: Arm B - Glecaprevir/Pibrentasvir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/362 (0%)		0/183 (0%)		0/182 (0%)
Serious Adverse Events
	DB Period: Arm A - Glecaprevir/Pibrentasvir		DB Period: Arm B - Placebo		OL Period: Arm B - Glecaprevir/Pibrentasvir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/362 (0.8%)		4/183 (2.2%)		5/182 (2.7%)
Eye disorders
Retinal detachment	0/362 (0%)	0	0/183 (0%)	0	1/182 (0.5%)	1
Infections and infestations
Appendicitis	0/362 (0%)	0	1/183 (0.5%)	1	0/182 (0%)	0
Bronchitis	0/362 (0%)	0	0/183 (0%)	0	1/182 (0.5%)	1
Lung infection	0/362 (0%)	0	0/183 (0%)	0	1/182 (0.5%)	1
Peritonitis	0/362 (0%)	0	1/183 (0.5%)	1	0/182 (0%)	0
Urinary tract infection	1/362 (0.3%)	1	0/183 (0%)	0	0/182 (0%)	0
Injury, poisoning and procedural complications
Avulsion fracture	1/362 (0.3%)	1	0/183 (0%)	0	0/182 (0%)	0
Fall	1/362 (0.3%)	1	0/183 (0%)	0	0/182 (0%)	0
Hand fracture	1/362 (0.3%)	1	0/183 (0%)	0	0/182 (0%)	0
Joint dislocation	1/362 (0.3%)	1	0/183 (0%)	0	0/182 (0%)	0
Ligament rupture	0/362 (0%)	0	1/183 (0.5%)	1	0/182 (0%)	0
Skin abrasion	0/362 (0%)	0	0/183 (0%)	0	1/182 (0.5%)	1
Soft tissue injury	0/362 (0%)	0	0/183 (0%)	0	1/182 (0.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer	0/362 (0%)	0	2/183 (1.1%)	2	0/182 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchiectasis	0/362 (0%)	0	0/183 (0%)	0	1/182 (0.5%)	1
Nasal cyst	0/362 (0%)	0	0/183 (0%)	0	1/182 (0.5%)	1
Vascular disorders
Hypertension	1/362 (0.3%)	1	0/183 (0%)	0	0/182 (0%)	0
Other (Not Including Serious) Adverse Events
	DB Period: Arm A - Glecaprevir/Pibrentasvir		DB Period: Arm B - Placebo		OL Period: Arm B - Glecaprevir/Pibrentasvir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/362 (9.9%)		18/183 (9.8%)		22/182 (12.1%)
Infections and infestations
Upper respiratory tract infection	36/362 (9.9%)	36	18/183 (9.8%)	18	22/182 (12.1%)	22

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.