VOYAGE-2: Efficacy and Safety of Glecaprevir/Pibrentasvir (ABT-493/ABT-530) in Treatment-Naive and Treatment-Experienced Asian Adults With Chronic Hepatitis C Virus Genotype (GT) 1 to GT6 Infection With Compensated Cirrhosis and With or Without Human Immunodeficiency Virus Co-Infection

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03235349
• Collaborator: (none)
• Enrollment: 160
• Locations: 34
• Arm: 1
• Actual Duration (Months): 16.9
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 160 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Treatment-Naïve and Treatment-Experienced Asian Adults With Chronic Hepatitis C Virus Genotype (GT) 1 to GT6 Infection With Compensated Cirrhosis and With or Without Human Immunodeficiency Virus Co-Infection
• Actual Study Start Date: Sep 29, 2017
• Actual Primary Completion Date: Nov 15, 2018
• Actual Study Completion Date: Feb 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glecaprevir/Pibrentasvir Participants received oral glecaprevir/pibrentasvir 300 mg/120 mg once daily (QD) for 12 or 16 weeks. Participants received treatment for 12 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™

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) [12 weeks after the last actual dose of study drug, Week 24 or Week 28 depending on the treatment regimen.]

   SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; 15 IU/mL) 12 weeks after the last dose of study drug.

Secondary Outcome Measures

1. Percentage of Participants With On-treatment Virologic Failure [12 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 With Post-treatment Relapse [From the end of treatment (Week 12 or 16) through 12 weeks after the last dose of study drug (Weeks 24 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 Achieving SVR12 [12 weeks after the last actual dose of study drug, Week 24 or Week 28 depending on the treatment regimen]

   SVR12 was defined as plasma HCV RNA level less than LLOQ (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) greater than or equal to 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 (RBV) OR sofosbuvir with RBV with or without IFN. Previous treatment must have been completed >= 8 weeks prior to screening.

• Compensated cirrhosis defined as Child-Pugh score of ≤ 6 at Screening and no current or past clinical evidence of Child-Pugh B or C Classification or clinical history of liver decompensation including ascites noted on physical exam, bleeding varices, use of diuretics for ascites, or hepatic encephalopathy.

• Absence of hepatocellular carcinoma (HCC)

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+ % >= 29%), or

• 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# 156851	Beijing	Beijing	China	100044
2	Guangzhou Eighth People's Hosp /ID# 156865	Guangzhou	Guangdong	China	510060
3	Guangdong General Hospital /ID# 156827	Guangzhou	Guangdong	China	510080
4	Nanfang Hospital of Southern Medical University /ID# 156866	Guangzhou	Guangdong	China	510515
5	The Third Affiliated Hospital Of Sun Yat-Sen University /ID# 156905	Guangzhou	Guangdong	China	510630
6	The Second Hospital of Nanjing /ID# 156869	Nanjing	Jiangsu	China	210003
7	Jiangsu Province People's Hospital /ID# 156867	Nanjing	Jiangsu	China	210029
8	The First Hosp of Jilin Univ /ID# 156825	Changchun	Jilin	China	130021
9	The Sixth People's Hospital of Shenyang /ID# 156854	Shenyang	Liaoning	China	110006
10	Ruijin Hospital, Shanghai Jiaotong /ID# 157337	Shanghai	Shanghai	China	200025
11	Huashan Hospital of Fudan University /ID# 156909	Shanghai	Shanghai	China	200040
12	Shanghai Public Health Cli Ctr /ID# 156837	Shanghai	Shanghai	China	201508
13	West China Hospital /ID# 156835	Chengdu	Sichuan	China	610041
14	Beijing Di Tan Hospital, Capital Medical University /ID# 156852	Beijing		China	100015
15	1st Hospital of Peking Uni /ID# 156850	Beijing		China	100034
16	Beijing Friendship Hospital /ID# 156843	Beijing		China	100050
17	Beijing Youan Hosp, Cap Med Un /ID# 163418	Beijing		China	100069
18	2nd Affiliated Hosp Chongqing /ID# 156838	Chongqing		China	400010
19	Mengchao Hepatobiliary Hospita /ID# 156907	Fuzhou		China	350025
20	Chinese People's Liberation Army 81 Hospital /ID# 156868	Nanjing		China	210002
21	Shengjing Hospital of China Medical University /ID# 156829	Shenyang		China	110004
22	1st Aff Hosp Xinjiang Med Uni /ID# 156891	Urumqi		China	830054
23	Fourth Military Medical University Tangdu Hospital, PLA /ID# 156767	Xi'an		China	710038
24	First Affiliated Hospital of Medical College of Xi'an Jiaotong University /ID# 163420	Xi'an		China	710061
25	Henan Provincial Peoples Hosp /ID# 157371	Zhengzhou, Henan		China	450000
26	Pusan National University Hosp /ID# 163411	Busan	Busan Gwang Yeogsi	Korea, Republic of	602-739
27	Seoul National Univ Bundang ho /ID# 163408	Seongnam	Gyeonggido	Korea, Republic of	13620
28	Inje University Busan Paik Hospital /ID# 163384	Busan	Gyeongsangbugdo	Korea, Republic of	47392
29	Pusan Nat Univ Yangsan Hosp /ID# 163385	Yangsan-si,	Gyeongsangnamdo	Korea, Republic of	50612
30	Severance Hospital /ID# 163399	Seoul	Seoul Teugbyeolsi	Korea, Republic of	03722
31	Samsung Medical Center /ID# 163402	Seoul	Seoul Teugbyeolsi	Korea, Republic of	06351
32	Korea University Guro Hospital /ID# 163412	Seoul	Seoul Teugbyeolsi	Korea, Republic of	08308
33	Seoul National University Hospital /ID# 163401	Seoul		Korea, Republic of	03080
34	Asan Medical Center /ID# 163398	Seoul		Korea, Republic of	05505

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc., AbbVie

Study Documents (Full-Text)

• Study Protocol - Apr 3, 2017
• Statistical Analysis Plan - Jan 18, 2018

More Information

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT03235349
• Other Study ID Numbers: M15-593
• First Posted: Aug 1, 2017
• Last Update Posted: Nov 21, 2019
• Last Verified: Aug 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; Cirrhosis; Compensated Cirrhosis; Human Immunodeficiency Virus; co-infection; Treatment-naïve; treatment-experienced; interferon; Asian
• Additional relevant MeSH terms: Infections; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Acquired Immunodeficiency Syndrome; HIV Infections; Coinfection; Hepatitis; Hepatitis, Chronic; Liver Cirrhosis; Immunologic Deficiency Syndromes; Fibrosis

Study Results

Participant Flow

Recruitment Details	The study was conducted at 34 sites in China and South Korea. Eligible participants were chronic hepatitis C (HCV) genotype (GT)1-6-infected adults with compensated cirrhosis 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.

Arm/Group Title	Glecaprevir/Pibrentasvir
Arm/Group Description	Participants received oral glecaprevir/pibrentasvir 300 mg/120 mg once daily (QD) for 12 or 16 weeks. Participants received treatment for 12 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks.
Period Title: Overall Study
STARTED	160
COMPLETED	158
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Glecaprevir/Pibrentasvir
Arm/Group Description	Participants received oral glecaprevir/pibrentasvir 300 mg/120 mg once daily (QD) for 12 or 16 weeks. Participants received treatment for 12 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks.
Overall Participants	160
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.83 (11.27)
Age, Customized (Count of Participants)
< 65 years	120 75%
≥ 65 years	40 25%
Sex: Female, Male (Count of Participants)
Female	80 50%
Male	80 50%
Race/Ethnicity, Customized (Count of Participants)
Asian	160 100%
Region of Enrollment (Count of Participants)
South Korea	37 23.1%
China	123 76.9%
HCV Genotype (Count of Participants)
Genotype 1	85 53.1%
Genotype 2	53 33.1%
Genotype 3	14 8.8%
Genotype 4	1 0.6%
Genotype 5	0 0%
Genotype 6	7 4.4%
Prior HCV Treatment History (Count of Participants)
Treatment-naive	110 68.8%
Treatment-experienced	50 31.3%
HCV Ribonucleic Acid (RNA) Level (log₁₀ IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log₁₀ IU/mL]	6.16 (0.74)
Human Immunodeficiency Virus (HIV) Co-infection Status (Count of Participants)
Hepatitis C infection only	160 100%
HCV / HIV co-infection	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
Description	SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; 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 24 or Week 28 depending on the treatment regimen.

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 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	Glecaprevir/Pibrentasvir
Arm/Group Description	Participants received oral glecaprevir/pibrentasvir 300 mg/120 mg once daily (QD) for 12 or 16 weeks. Participants received treatment for 12 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks.
Measure Participants	160
Number (95% Confidence Interval) [percentage of participants]	99.4 62.1%

2. Secondary Outcome

Title	Percentage of Participants 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	12 or 16 weeks depending on the treatment regimen

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	Glecaprevir/Pibrentasvir
Arm/Group Description	Participants received oral glecaprevir/pibrentasvir 300 mg/120 mg once daily (QD) for 12 or 16 weeks. Participants received treatment for 12 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks.
Measure Participants	160
Number (95% Confidence Interval) [percentage of participants]	0.0 0%

3. Secondary Outcome

Title	Percentage of Participants 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 (Week 12 or 16) through 12 weeks after the last dose of study drug (Weeks 24 or 28 depending on the treatment regimen).

Outcome Measure Data

Analysis Population Description

All enrolled participants 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	Glecaprevir/Pibrentasvir
Arm/Group Description	Participants received oral glecaprevir/pibrentasvir 300 mg/120 mg once daily (QD) for 12 or 16 weeks. Participants received treatment for 12 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks.
Measure Participants	159
Number (95% Confidence Interval) [percentage of participants]	0.6 0.4%

4. Secondary Outcome

Title	Percentage of HCV/HIV Co-infected Participants Achieving SVR12
Description	SVR12 was defined as plasma HCV RNA level less than LLOQ (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 24 or Week 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	Glecaprevir/Pibrentasvir
Arm/Group Description	Participants received oral glecaprevir/pibrentasvir 300 mg/120 mg once daily (QD) for 12 or 16 weeks. Participants received treatment for 12 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks.
Measure Participants	0

Adverse Events

Time Frame	From initiation of study drug through 30 days after last dose; up to 16 or 20 weeks depending on the treatment regimen.
Arm/Group Title	Glecaprevir/Pibrentasvir
Arm/Group Description	Participants received oral glecaprevir/pibrentasvir 300 mg/120 mg once daily (QD) for 12 or 16 weeks. Participants received treatment for 12 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks.
All Cause Mortality
	Glecaprevir/Pibrentasvir
	Affected / at Risk (%)	# Events
Total	1/160 (0.6%)
Serious Adverse Events
	Glecaprevir/Pibrentasvir
	Affected / at Risk (%)	# Events
Total	5/160 (3.1%)
Gastrointestinal disorders
UPPER GASTROINTESTINAL HAEMORRHAGE	1/160 (0.6%)	1
Hepatobiliary disorders
BILE DUCT STONE	1/160 (0.6%)	1
HEPATIC LESION	1/160 (0.6%)	1
Infections and infestations
LIVER ABSCESS	1/160 (0.6%)	1
Psychiatric disorders
DEPRESSION	1/160 (0.6%)	1
Other (Not Including Serious) Adverse Events
	Glecaprevir/Pibrentasvir
	Affected / at Risk (%)	# Events
Total	29/160 (18.1%)
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION	19/160 (11.9%)	19
URINARY TRACT INFECTION	10/160 (6.3%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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.