Trial Outcomes & Findings for A Study of Glecaprevir (GLE)/Pibrentasvir (PIB) in Treatment-Naive Adults With Chronic Hepatitis C Virus (HCV) Genotype 1-6 Infection and Compensated Cirrhosis (NCT NCT03089944)

Results Overview

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. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% confidence interval (CI) for the percentage of participants with HCV GT1, GT2, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 94% in the PP population. Efficacy analyses were performed following a fixed-sequence testing procedure to control the type I error rate. The percentage of participants achieving SVR12 was summarized with a 2-sided 95% CI, calculated using the normal approximation to the binomial distribution. If the number of participants who failed to achieve SVR12 rate was less than 5, the Wilson's score method was used to calculate the CI.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

343 participants

Primary outcome timeframe

12 weeks after last dose of study drug

Results posted on

2020-07-13

Participant Flow

A total of 343 participants were enrolled and received ≥ 1 dose of study drug.

Participant milestones

Participant milestones
Measure	Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks GLE/PIB 300 mg/120 mg once daily (QD) for 8 weeks.
Overall Study STARTED	343
Overall Study COMPLETED	331
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks GLE/PIB 300 mg/120 mg once daily (QD) for 8 weeks.
Overall Study Lost to Follow-up	8
Overall Study Withdrew Consent	2
Overall Study Adverse Event	1
Overall Study Other	1

Baseline Characteristics

A Study of Glecaprevir (GLE)/Pibrentasvir (PIB) in Treatment-Naive Adults With Chronic Hepatitis C Virus (HCV) Genotype 1-6 Infection and Compensated Cirrhosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks n=343 Participants GLE/PIB 300 mg/120 mg once daily (QD) for 8 weeks.
Age, Continuous	57.61 years STANDARD_DEVIATION 10.58 • n=5 Participants
Sex: Female, Male Female	126 Participants n=5 Participants
Sex: Female, Male Male	217 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	300 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	28 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	28 Participants n=5 Participants
Race (NIH/OMB) White	285 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks after last dose of study drug

Population: Per Protocol (PP) Population: All participants who received at least one dose of study drug, with the exception of participants who experienced breakthrough, or prematurely discontinued treatment prior to Week 8, or had no HCV RNA value in the SVR12 visit window or later.

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. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% confidence interval (CI) for the percentage of participants with HCV GT1, GT2, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 94% in the PP population. Efficacy analyses were performed following a fixed-sequence testing procedure to control the type I error rate. The percentage of participants achieving SVR12 was summarized with a 2-sided 95% CI, calculated using the normal approximation to the binomial distribution. If the number of participants who failed to achieve SVR12 rate was less than 5, the Wilson's score method was used to calculate the CI.

Outcome measures

Outcome measures
Measure	Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks n=274 Participants GLE/PIB 300 mg/120 mg once daily (QD) for 8 weeks.
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Hepatitis C Virus (HCV) Genotype (GT) 1,2,4,5 and 6-infected Participants in the Per Protocol (PP) Population	100 percentage of participants Interval 98.6 to 100.0

PRIMARY outcome

Timeframe: 12 weeks after last dose of study drug

Population: Intent to treat (ITT) population: Participants who received at least one dose of study drug.

SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 93% in the ITT population. Primary efficacy analyses were performed following a fixed-sequence testing procedure to control the type I error rate. The percentage of participants achieving SVR12 was summarized with a 2-sided 95% CI, calculated using the normal approximation to the binomial distribution. If the number of participants who failed to achieve SVR12 rate was less than 5, the Wilson's score method was used to calculate the CI.

Outcome measures

Outcome measures
Measure	Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks n=280 Participants GLE/PIB 300 mg/120 mg once daily (QD) for 8 weeks.
Percentage of Participants With SVR12 in HCV GT 1,2,4,5 and 6-infected Participants in the Intent-To-Treat (ITT) Population	98.2 percentage of participants Interval 96.7 to 99.8

SECONDARY outcome

Timeframe: 12 weeks after last dose of study drug

Population: PP population

SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT3, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 94% in the PP population. These efficacy analyses were performed only if success was demonstrated for both primary efficacy analyses, following a fixed-sequence testing procedure.

Outcome measures

Outcome measures
Measure	Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks n=335 Participants GLE/PIB 300 mg/120 mg once daily (QD) for 8 weeks.
Percentage of Participants With SVR12 in HCV GT1-6-infected Participants in the PP Population	99.7 percentage of participants Interval 98.3 to 99.9

SECONDARY outcome

Timeframe: 12 weeks after the last dose of study drug

Population: ITT population

SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT3, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 93% in the ITT population. These efficacy analyses were performed only if success was demonstrated for both primary efficacy analyses, following a fixed-sequence testing procedure.

Outcome measures

Outcome measures
Measure	Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks n=343 Participants GLE/PIB 300 mg/120 mg once daily (QD) for 8 weeks.
Percentage of Participants With SVR12 in HCV GT1-6-infected Participants in the ITT Population	97.7 percentage of participants Interval 96.1 to 99.3

SECONDARY outcome

Timeframe: 8 weeks on treatment

Population: ITT population

On-treatment virologic failure was defined as confirmed HCV RNA ≥ 100 IU/mL after HCV RNA \< LLOQ during treatment; confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment.

Outcome measures

Outcome measures
Measure	Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks n=343 Participants GLE/PIB 300 mg/120 mg once daily (QD) for 8 weeks.
Percentage of Participants With On-treatment Virologic Failure in the ITT Population	0 percentage of participants Interval 0.0 to 1.1

SECONDARY outcome

Timeframe: Up to 12 weeks after the last dose of study drug

Population: ITT population

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 as planned (defined as study drug duration ≥ 52 days for participants assigned to 8 weeks of treatment) and with HCV RNA levels \< LLOQ at the end of treatment excluding participants who had been reinfected.

Outcome measures

Outcome measures
Measure	Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks n=336 Participants GLE/PIB 300 mg/120 mg once daily (QD) for 8 weeks.
Percentage of Participants With Post-treatment Relapse	0.3 percentage of participants Interval 0.1 to 1.7

SECONDARY outcome

Timeframe: 12 weeks after the last dose of study drug

Population: PP population

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

Outcome measures

Outcome measures
Measure	Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks n=61 Participants GLE/PIB 300 mg/120 mg once daily (QD) for 8 weeks.
Percentage of HCV GT3-infected Participants Who Achieved SVR12 in the PP Population	98.4 percentage of participants Interval 91.3 to 99.7

SECONDARY outcome

Timeframe: 12 weeks after the last dose of study drug

Population: ITT population

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

Outcome measures

Outcome measures
Measure	Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks n=63 Participants GLE/PIB 300 mg/120 mg once daily (QD) for 8 weeks.
Percentage of HCV GT3-infected Participants Who Achieved SVR12 in the ITT Population	95.2 percentage of participants Interval 86.9 to 98.4

Adverse Events

Glecaprevir (GLE)/Pibrentasvir (PIB)

Serious events: 6 serious events

Other events: 82 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Glecaprevir (GLE)/Pibrentasvir (PIB) n=343 participants at risk GLE/PIB 300 mg/120 mg once daily (QD) for 8 weeks.
Cardiac disorders ATRIAL FIBRILLATION	0.29% 1/343 • Number of events 1 • Treatment emergent adverse events (TEAEs) were defined as any adverse event with an onset date that was on or after the first dose of study drug and no more than 30 days after the last dose of study drug.
Cardiac disorders CARDIAC FAILURE	0.29% 1/343 • Number of events 1 • Treatment emergent adverse events (TEAEs) were defined as any adverse event with an onset date that was on or after the first dose of study drug and no more than 30 days after the last dose of study drug.
Gastrointestinal disorders DUODENAL ULCER HAEMORRHAGE	0.29% 1/343 • Number of events 1 • Treatment emergent adverse events (TEAEs) were defined as any adverse event with an onset date that was on or after the first dose of study drug and no more than 30 days after the last dose of study drug.
General disorders OEDEMA PERIPHERAL	0.29% 1/343 • Number of events 1 • Treatment emergent adverse events (TEAEs) were defined as any adverse event with an onset date that was on or after the first dose of study drug and no more than 30 days after the last dose of study drug.
Infections and infestations BRONCHITIS	0.29% 1/343 • Number of events 1 • Treatment emergent adverse events (TEAEs) were defined as any adverse event with an onset date that was on or after the first dose of study drug and no more than 30 days after the last dose of study drug.
Infections and infestations PNEUMONIA	0.29% 1/343 • Number of events 1 • Treatment emergent adverse events (TEAEs) were defined as any adverse event with an onset date that was on or after the first dose of study drug and no more than 30 days after the last dose of study drug.
Infections and infestations PYELONEPHRITIS	0.29% 1/343 • Number of events 1 • Treatment emergent adverse events (TEAEs) were defined as any adverse event with an onset date that was on or after the first dose of study drug and no more than 30 days after the last dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) ADENOCARCINOMA GASTRIC	0.29% 1/343 • Number of events 1 • Treatment emergent adverse events (TEAEs) were defined as any adverse event with an onset date that was on or after the first dose of study drug and no more than 30 days after the last dose of study drug.

Other adverse events

Other adverse events
Measure	Glecaprevir (GLE)/Pibrentasvir (PIB) n=343 participants at risk GLE/PIB 300 mg/120 mg once daily (QD) for 8 weeks.
Gastrointestinal disorders NAUSEA	5.5% 19/343 • Number of events 19 • Treatment emergent adverse events (TEAEs) were defined as any adverse event with an onset date that was on or after the first dose of study drug and no more than 30 days after the last dose of study drug.
General disorders FATIGUE	8.7% 30/343 • Number of events 30 • Treatment emergent adverse events (TEAEs) were defined as any adverse event with an onset date that was on or after the first dose of study drug and no more than 30 days after the last dose of study drug.
Nervous system disorders HEADACHE	8.2% 28/343 • Number of events 28 • Treatment emergent adverse events (TEAEs) were defined as any adverse event with an onset date that was on or after the first dose of study drug and no more than 30 days after the last dose of study drug.
Skin and subcutaneous tissue disorders PRURITUS	8.5% 29/343 • Number of events 29 • Treatment emergent adverse events (TEAEs) were defined as any adverse event with an onset date that was on or after the first dose of study drug and no more than 30 days after the last dose of study drug.

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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