Trial Outcomes & Findings for Efficacy and Safety of 8-weeks of Glecaprevir/Pibrentasvir in Treatment-Naïve Adults With HCV Genotype 1-6 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) ≤1 (NCT NCT03212521)

Last Updated: 2019-09-04

Results Overview

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. The 95% confidence interval (95%CI) was calculated using the Wilson's score method. Efficacy was to be established if the lower bound of the 95%CI was greater than the threshold of 92.4%, based on the historical rate observed in glecaprevir/pibrentasvir registrational studies in treatment-naïve, non-cirrhotic patients (98.4%) minus a margin of 6%.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

230 participants

Primary outcome timeframe

12 weeks after the last actual dose of study drug, Week 20

Results posted on

2019-09-04

Participant Flow

Participants were enrolled at 40 sites in Bulgaria, Canada, France, Germany, Poland, Russian Federation, Spain, United Kingdom, and the United States (including Puerto Rico).

Participant milestones

Participant milestones
Measure	Glecaprevir/Pibrentasvir Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 weeks.
Overall Study STARTED	230
Overall Study COMPLETED	223
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Glecaprevir/Pibrentasvir Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 weeks.
Overall Study Adverse Event	1
Overall Study Lost to Follow-up	4
Overall Study Withdrawal by Subject	1
Overall Study Other	1

Baseline Characteristics

Efficacy and Safety of 8-weeks of Glecaprevir/Pibrentasvir in Treatment-Naïve Adults With HCV Genotype 1-6 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) ≤1

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glecaprevir/Pibrentasvir n=230 Participants Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 weeks.
Age, Continuous	48 years n=5 Participants
Sex: Female, Male Female	113 Participants n=5 Participants
Sex: Female, Male Male	117 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	205 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized White	207 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	13 Participants n=5 Participants
Race/Ethnicity, Customized Asian	10 Participants n=5 Participants
Hepatitis C Virus (HCV) Genotype Genotype 1	151 Participants n=5 Participants
Hepatitis C Virus (HCV) Genotype Genotype 2	33 Participants n=5 Participants
Hepatitis C Virus (HCV) Genotype Genotype 3	35 Participants n=5 Participants
Hepatitis C Virus (HCV) Genotype Genotype 4	9 Participants n=5 Participants
Hepatitis C Virus (HCV) Genotype Genotype 5	0 Participants n=5 Participants
Hepatitis C Virus (HCV) Genotype Genotype 6	2 Participants n=5 Participants
Aminotransferase/Platelet Ratio Index (APRI)	0.41 ratio n=5 Participants
HCV Ribonucleic Acid (RNA) Concentration	6.29 Log₁₀ IU/mL n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks after the last actual dose of study drug, Week 20

Population: The modified intention-to-treat (mITT) population includes all enrolled participants who received at least 1 dose of study drug, excluding participants who did not achieve SVR12 for reasons other than virologic failure, such as missing SVR12 data (5 participants) or premature study drug discontinuation (3 participants).

Outcome measures

Outcome measures
Measure	Glecaprevir/Pibrentasvir n=222 Participants Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 weeks.
Percentage of Participants in the Modified Intention-to-Treat Population With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)	100.0 percentage of participants Interval 98.3 to 100.0

SECONDARY outcome

Timeframe: 12 weeks after the last actual dose of study drug, Week 20

Population: The intention-to-treat (ITT) population included all enrolled participants who received at least 1 dose of study drug.

SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the LLOQ (15 IU/mL) 12 weeks after the last dose of study drug. The 95% confidence interval was calculated using the normal approximation to the binomial distribution. Efficacy was to be established if the lower bound of the 95%CI was greater than the threshold of 91.4%, based on the mITT threshold minus an expected 1% rate of non-virological SVR failures.

Outcome measures

Outcome measures
Measure	Glecaprevir/Pibrentasvir n=230 Participants Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 weeks.
Percentage of Participants in the Intention-to-Treat Population With SVR12	96.5 percentage of participants Interval 94.2 to 98.9

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: Intention-to-treat population

On-treatment virologic failure was defined as one of the following conditions: * confirmed HCV RNA ≥ 100 IU/mL after HCV RNA \< 15 IU/mL during the Treatment Period; or * 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 * HCV RNA ≥ 15 IU/mL at end of treatment with at least 6 weeks of treatment, where the HCV RNA value must be collected on or after Study Drug Day 36 and study drug duration ≥ 36 days.

Outcome measures

Outcome measures
Measure	Glecaprevir/Pibrentasvir n=230 Participants Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 weeks.
Percentage of Participants With On-treatment Virologic Failure	0.0 percentage of participants Interval 0.0 to 1.6

SECONDARY outcome

Timeframe: From the end of treatment (Week 8) through 12 weeks after the last dose of study drug (Week 20)

Population: Intention-to-treat population 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 ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels \< LLOQ at the end of treatment.

Outcome measures

Outcome measures
Measure	Glecaprevir/Pibrentasvir n=225 Participants Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 weeks.
Percentage of Participants With Post-treatment Relapse	0.0 percentage of participants Interval 0.0 to 1.7

Adverse Events

Glecaprevir/Pibrentasvir

Serious events: 4 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Glecaprevir/Pibrentasvir n=230 participants at risk Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 weeks.
Injury, poisoning and procedural complications JOINT DISLOCATION	0.43% 1/230 • Number of events 1 • From first dose of study drug through 30 days after the last dose of study drug; 12 weeks
Injury, poisoning and procedural complications LIMB TRAUMATIC AMPUTATION	0.43% 1/230 • Number of events 1 • From first dose of study drug through 30 days after the last dose of study drug; 12 weeks
Reproductive system and breast disorders UTERINE HAEMORRHAGE	0.43% 1/230 • Number of events 1 • From first dose of study drug through 30 days after the last dose of study drug; 12 weeks
Skin and subcutaneous tissue disorders ANGIOEDEMA	0.87% 2/230 • Number of events 2 • From first dose of study drug through 30 days after the last dose of study drug; 12 weeks

Other adverse events

Other adverse events
Measure	Glecaprevir/Pibrentasvir n=230 participants at risk Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 weeks.
General disorders FATIGUE	7.4% 17/230 • Number of events 17 • From first dose of study drug through 30 days after the last dose of study drug; 12 weeks
Nervous system disorders HEADACHE	12.6% 29/230 • Number of events 29 • From first dose of study drug through 30 days after the last dose of study drug; 12 weeks

Additional Information

Global Medical Services

AbbVie

Phone: 800-633-9110

Email: [email protected]

Results disclosure agreements

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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