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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)

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ClinicalTrials.gov Identifier: NCT03222583
Recruitment Status : Completed
First Posted : July 19, 2017
Results First Posted : December 23, 2019
Last Update Posted : December 23, 2019
Sponsor:
Information provided by (Responsible Party):
AbbVie

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hepatitis C Virus (HCV)
Interventions Drug: Placebo
Drug: Glecaprevir/Pibrentasvir
Enrollment 546
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 Details 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
Hide 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 [1] 0 182
Completed Open-label Period 0 181
Completed 358 177
Not Completed 5 6
Reason Not Completed
Withdrawal by Subject             3             3
Lost to Follow-up             1             0
Other             1             3
[1]
The open-label treatment period was only applicable for participants assigned to Arm B (placebo).
Arm/Group Title Arm A: Glecaprevir/Pibrentasvir Arm B: Placebo / Glecaprevir/Pibrentasvir Total
Hide 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 Number of Baseline Participants 362 183 545
Hide Baseline Analysis Population Description
The safety population included all participants who received at least 1 dose of study drug during the DB Treatment Period
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 362 participants 183 participants 545 participants
48.68  (12.96) 49.18  (13.55) 48.85  (13.15)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 362 participants 183 participants 545 participants
Female
180
  49.7%
97
  53.0%
277
  50.8%
Male
182
  50.3%
86
  47.0%
268
  49.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Asian Number Analyzed 362 participants 183 participants 545 participants
362
 100.0%
183
 100.0%
545
 100.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 362 participants 183 participants 545 participants
South Korea
82
  22.7%
42
  23.0%
124
  22.8%
Singapore
21
   5.8%
11
   6.0%
32
   5.9%
China
259
  71.5%
130
  71.0%
389
  71.4%
HCV Genotype  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 362 participants 183 participants 545 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
   0.0%
1
   0.5%
1
   0.2%
Genotype 5
0
   0.0%
0
   0.0%
0
   0.0%
Genotype 6
18
   5.0%
12
   6.6%
30
   5.5%
Prior HCV Treatment History   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 362 participants 183 participants 545 participants
Treatment-naive
281
  77.6%
155
  84.7%
436
  80.0%
Treatment-experienced
81
  22.4%
28
  15.3%
109
  20.0%
[1]
Measure Description: Treatment-experienced includes treatment with interferon (IFN; alpha, beta or pegylated interferon [pegIFN]) with or without ribavirin (RBV), OR sofosbuvir with RBV with or without IFN.
Human Immunodeficiency Virus (HIV) Co-infection Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 362 participants 183 participants 545 participants
Hepatitis C infection only
362
 100.0%
183
 100.0%
545
 100.0%
HCV / HIV co-infection
0
   0.0%
0
   0.0%
0
   0.0%
HCV Ribonucleic Acid (RNA) Level  
Mean (Standard Deviation)
Unit of measure:  Log₁₀ IU/mL
Number Analyzed 362 participants 183 participants 545 participants
6.37  (0.72) 6.26  (0.79) 6.33  (0.74)
1.Primary Outcome
Title Percentage of HCV GT1 - GT6-Infected Participants in Arm A Who Achieved Sustained Virologic Response 12 Weeks Post Treatment (SVR12)
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 362
Measure Type: Number
Unit of Measure: percentage of participants
97.2
Hide 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%.
Method of Estimation Estimation Parameter Percentage of Participants with SVR12
Estimated Value 97.2
Confidence Interval (2-Sided) 95%
95.5 to 98.9
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of HCV GT1-Infected Participants in Arm A Who Achieved SVR12
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 179
Measure Type: Number
Unit of Measure: percentage of participants
99.4
Hide 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%.
Method of Estimation Estimation Parameter Percentage of Participants with SVR12
Estimated Value 99.4
Confidence Interval (2-Sided) 95%
98.3 to 100.0
Estimation Comments [Not Specified]
3.Primary Outcome
Title Percentage of HCV GT2-Infected Participants in Arm A Who Achieved SVR12
Hide 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.
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 139
Measure Type: Number
Unit of Measure: percentage of participants
97.8
Hide 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%.
Method of Estimation Estimation Parameter Percentage of Participants with SVR12
Estimated Value 97.8
Confidence Interval (2-Sided) 95%
95.4 to 100.0
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants in Arm A With On-treatment Virologic Failure
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 362
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.6
(0.2 to 2.0)
5.Secondary Outcome
Title Percentage of Participants in Arm A With Post-treatment Relapse
Hide 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).
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 359
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1.7
(0.8 to 3.6)
6.Secondary Outcome
Title Percentage of HCV/HIV Co-infected Participants in Arm A Who Achieved SVR12
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
No HCV-HIV co-infected participants were enrolled in the study
Arm/Group Title Arm A: Glecaprevir/Pibrentasvir
Hide 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.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title DB Period: Arm A - Glecaprevir/Pibrentasvir DB Period: Arm B - Placebo OL Period: Arm B - Glecaprevir/Pibrentasvir
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/362 (0.00%)      0/183 (0.00%)      0/182 (0.00%)    
Hide 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 (0.83%)      4/183 (2.19%)      5/182 (2.75%)    
Eye disorders       
Retinal detachment  1  0/362 (0.00%)  0 0/183 (0.00%)  0 1/182 (0.55%)  1
Infections and infestations       
Appendicitis  1  0/362 (0.00%)  0 1/183 (0.55%)  1 0/182 (0.00%)  0
Bronchitis  1  0/362 (0.00%)  0 0/183 (0.00%)  0 1/182 (0.55%)  1
Lung infection  1  0/362 (0.00%)  0 0/183 (0.00%)  0 1/182 (0.55%)  1
Peritonitis  1  0/362 (0.00%)  0 1/183 (0.55%)  1 0/182 (0.00%)  0
Urinary tract infection  1  1/362 (0.28%)  1 0/183 (0.00%)  0 0/182 (0.00%)  0
Injury, poisoning and procedural complications       
Avulsion fracture  1  1/362 (0.28%)  1 0/183 (0.00%)  0 0/182 (0.00%)  0
Fall  1  1/362 (0.28%)  1 0/183 (0.00%)  0 0/182 (0.00%)  0
Hand fracture  1  1/362 (0.28%)  1 0/183 (0.00%)  0 0/182 (0.00%)  0
Joint dislocation  1  1/362 (0.28%)  1 0/183 (0.00%)  0 0/182 (0.00%)  0
Ligament rupture  1  0/362 (0.00%)  0 1/183 (0.55%)  1 0/182 (0.00%)  0
Skin abrasion  1  0/362 (0.00%)  0 0/183 (0.00%)  0 1/182 (0.55%)  1
Soft tissue injury  1  0/362 (0.00%)  0 0/183 (0.00%)  0 1/182 (0.55%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Papillary thyroid cancer  1  0/362 (0.00%)  0 2/183 (1.09%)  2 0/182 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Bronchiectasis  1  0/362 (0.00%)  0 0/183 (0.00%)  0 1/182 (0.55%)  1
Nasal cyst  1  0/362 (0.00%)  0 0/183 (0.00%)  0 1/182 (0.55%)  1
Vascular disorders       
Hypertension  1  1/362 (0.28%)  1 0/183 (0.00%)  0 0/182 (0.00%)  0
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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 (9.94%)      18/183 (9.84%)      22/182 (12.09%)    
Infections and infestations       
Upper respiratory tract infection  1  36/362 (9.94%)  36 18/183 (9.84%)  18 22/182 (12.09%)  22
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Medical Services
Organization: AbbVie
Phone: 800-633-9110
EMail: abbvieclinicaltrials@abbvie.com
Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT03222583    
Other Study ID Numbers: M15-592
First Submitted: July 17, 2017
First Posted: July 19, 2017
Results First Submitted: October 16, 2019
Results First Posted: December 23, 2019
Last Update Posted: December 23, 2019