Trial Outcomes & Findings for 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 (NCT NCT03222583)

Last Updated: 2019-12-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

546 participants

Primary outcome timeframe

12 weeks after the last actual dose of study drug, Week 20 or Week 28 depending on the treatment regimen.

Results posted on

2019-12-23

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Arm A: 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.	Arm B: 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.
Overall Study STARTED	363	183
Overall Study Received Double-blind Treatment	362	183
Overall Study Completed Double-blind Period	360	183
Overall Study Entered Open-label Period	0	182
Overall Study Completed Open-label Period	0	181
Overall Study COMPLETED	358	177
Overall Study NOT COMPLETED	5	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: 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.	Arm B: 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.
Overall Study Withdrawal by Subject	3	3
Overall Study Lost to Follow-up	1	0
Overall Study Other	1	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Glecaprevir/Pibrentasvir n=362 Participants 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.	Arm B: Placebo / Glecaprevir/Pibrentasvir n=183 Participants 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 n=545 Participants Total of all reporting groups
Age, Continuous	48.68 years STANDARD_DEVIATION 12.96 • n=5 Participants	49.18 years STANDARD_DEVIATION 13.55 • n=7 Participants	48.85 years STANDARD_DEVIATION 13.15 • n=5 Participants
Sex: Female, Male Female	180 Participants n=5 Participants	97 Participants n=7 Participants	277 Participants n=5 Participants
Sex: Female, Male Male	182 Participants n=5 Participants	86 Participants n=7 Participants	268 Participants n=5 Participants
Race/Ethnicity, Customized Asian	362 Participants n=5 Participants	183 Participants n=7 Participants	545 Participants n=5 Participants
Region of Enrollment South Korea	82 Participants n=5 Participants	42 Participants n=7 Participants	124 Participants n=5 Participants
Region of Enrollment Singapore	21 Participants n=5 Participants	11 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment China	259 Participants n=5 Participants	130 Participants n=7 Participants	389 Participants n=5 Participants
HCV Genotype Genotype 1	179 Participants n=5 Participants	89 Participants n=7 Participants	268 Participants n=5 Participants
HCV Genotype Genotype 2	139 Participants n=5 Participants	71 Participants n=7 Participants	210 Participants n=5 Participants
HCV Genotype Genotype 3	26 Participants n=5 Participants	10 Participants n=7 Participants	36 Participants n=5 Participants
HCV Genotype Genotype 4	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
HCV Genotype Genotype 5	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
HCV Genotype Genotype 6	18 Participants n=5 Participants	12 Participants n=7 Participants	30 Participants n=5 Participants
Prior HCV Treatment History Treatment-naive	281 Participants n=5 Participants	155 Participants n=7 Participants	436 Participants n=5 Participants
Prior HCV Treatment History Treatment-experienced	81 Participants n=5 Participants	28 Participants n=7 Participants	109 Participants n=5 Participants
Human Immunodeficiency Virus (HIV) Co-infection Status Hepatitis C infection only	362 Participants n=5 Participants	183 Participants n=7 Participants	545 Participants n=5 Participants
Human Immunodeficiency Virus (HIV) Co-infection Status HCV / HIV co-infection	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
HCV Ribonucleic Acid (RNA) Level	6.37 log₁₀ IU/mL STANDARD_DEVIATION 0.72 • n=5 Participants	6.26 log₁₀ IU/mL STANDARD_DEVIATION 0.79 • n=7 Participants	6.33 log₁₀ IU/mL STANDARD_DEVIATION 0.74 • n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks after the last actual dose of study drug, Week 20 or Week 28 depending on the treatment regimen.

Population: 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.

Outcome measures

Outcome measures
Measure	Arm A: Glecaprevir/Pibrentasvir n=362 Participants 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.
Percentage of HCV GT1 - GT6-Infected Participants in Arm A Who Achieved Sustained Virologic Response 12 Weeks Post Treatment (SVR12)	97.2 percentage of participants

PRIMARY outcome

Timeframe: 12 weeks after last actual dose of study drug, Week 20 or Week 28 depending on the treatment regimen

Population: 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.

SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Arm A: Glecaprevir/Pibrentasvir n=179 Participants 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.
Percentage of HCV GT1-Infected Participants in Arm A Who Achieved SVR12	99.4 percentage of participants

PRIMARY outcome

Timeframe: 12 weeks after the last dose of study drug, Week 20 or Week 28 depending on the treatment regimen.

Population: 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.

SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last actual dose of study drug.

Outcome measures

Outcome measures
Measure	Arm A: Glecaprevir/Pibrentasvir n=139 Participants 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.
Percentage of HCV GT2-Infected Participants in Arm A Who Achieved SVR12	97.8 percentage of participants

SECONDARY outcome

Timeframe: 8 or 16 weeks depending on the treatment regimen

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Arm A: Glecaprevir/Pibrentasvir n=362 Participants 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.
Percentage of Participants in Arm A With On-treatment Virologic Failure	0.6 percentage of participants Interval 0.2 to 2.0

SECONDARY outcome

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).

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Arm A: Glecaprevir/Pibrentasvir n=359 Participants 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.
Percentage of Participants in Arm A With Post-treatment Relapse	1.7 percentage of participants Interval 0.8 to 3.6

SECONDARY outcome

Timeframe: 12 weeks after the last actual dose of study drug, Week 20 or 28 depending on the treatment regimen

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

SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last dose of study drug.

Outcome measures

Outcome data not reported

Adverse Events

DB Period: Arm A - Glecaprevir/Pibrentasvir

Serious events: 3 serious events

Other events: 36 other events

Deaths: 0 deaths

DB Period: Arm B - Placebo

Serious events: 4 serious events

Other events: 18 other events

Deaths: 0 deaths

OL Period: Arm B - Glecaprevir/Pibrentasvir

Serious events: 5 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	DB Period: Arm A - Glecaprevir/Pibrentasvir n=362 participants at risk 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.	DB Period: Arm B - Placebo n=183 participants at risk 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.	OL Period: Arm B - Glecaprevir/Pibrentasvir n=182 participants at risk 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.
Infections and infestations Upper respiratory tract infection	9.9% 36/362 • Number of events 36 • 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.	9.8% 18/183 • Number of events 18 • 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.	12.1% 22/182 • Number of events 22 • 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.

Additional Information

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Email: [email protected]

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Principal investigator is a sponsor employee 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.
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