Trial Outcomes & Findings for Multi-Center, Randomized, Open-Label Study of G/P +/- RBV for NS5A + SOF Previously Treated GT1 HCV Subjects (NCT NCT03092375)

Last Updated: 2020-02-26

Results Overview

Number of non-cirrhotic treatment-experienced HCV genotype 1 with a NS5Ai inhibitor + SOF +/-RBV participants with undetectable HCV RNA (HCV RNA \<Lower Limit of Quantification -LLOQ) 12 weeks after completing G/P 300 mg/100 mg daily for 12 weeks (Arm A) vs. 16 weeks of G/P 300 mg/100 mg daily (Arm B)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

177 participants

Primary outcome timeframe

Up to 28 weeks

Results posted on

2020-02-26

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A: G/P 300 mg/120 mg QD for 12 Wks Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks. Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm B: G/P 300 mg/120 mg QD for 16 Wks Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily Ribavirin 200Mg Tablet: Weight-based 1000-1200 mg	Arm D: G/P 300 mg/120 mg QD for 16 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily
Overall Study STARTED	78	49	21	29
Overall Study COMPLETED	78	48	20	29
Overall Study NOT COMPLETED	0	1	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: G/P 300 mg/120 mg QD for 12 Wks Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks. Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm B: G/P 300 mg/120 mg QD for 16 Wks Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily Ribavirin 200Mg Tablet: Weight-based 1000-1200 mg	Arm D: G/P 300 mg/120 mg QD for 16 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily
Overall Study Lack of Efficacy	0	1	1	0

Baseline Characteristics

Multi-Center, Randomized, Open-Label Study of G/P +/- RBV for NS5A + SOF Previously Treated GT1 HCV Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: G/P 300 mg/120 mg QD for 12 Wks n=78 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks. Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm B: G/P 300 mg/120 mg QD for 16 Wks n=49 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks n=21 Participants Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily Ribavirin 200Mg Tablet: Weight-based 1000-1200 mg	Arm D: G/P 300 mg/120 mg QD for 16 Wks n=29 Participants Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Total n=177 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	53 Participants n=5 Participants	31 Participants n=7 Participants	16 Participants n=5 Participants	16 Participants n=4 Participants	116 Participants n=21 Participants
Age, Categorical >=65 years	25 Participants n=5 Participants	18 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants	61 Participants n=21 Participants
Age, Continuous	60.99 years n=5 Participants	61.37 years n=7 Participants	59.10 years n=5 Participants	62.59 years n=4 Participants	61.3 years n=21 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	9 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	34 Participants n=21 Participants
Sex: Female, Male Male	64 Participants n=5 Participants	40 Participants n=7 Participants	16 Participants n=5 Participants	23 Participants n=4 Participants	143 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	32 Participants n=5 Participants	25 Participants n=7 Participants	8 Participants n=5 Participants	12 Participants n=4 Participants	77 Participants n=21 Participants
Race (NIH/OMB) White	44 Participants n=5 Participants	23 Participants n=7 Participants	12 Participants n=5 Participants	17 Participants n=4 Participants	96 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Region of Enrollment United States	78 participants n=5 Participants	49 participants n=7 Participants	21 participants n=5 Participants	29 participants n=4 Participants	180 participants n=21 Participants
HCV Genotype, non-1b	60 Participants n=5 Participants	39 Participants n=7 Participants	17 Participants n=5 Participants	26 Participants n=4 Participants	142 Participants n=21 Participants
HCV RNA	6.4 LOG10 IU/mL n=5 Participants	6.4 LOG10 IU/mL n=7 Participants	6.3 LOG10 IU/mL n=5 Participants	6.4 LOG10 IU/mL n=4 Participants	6.4 LOG10 IU/mL n=21 Participants
PLATELET	204.50 10E3 cells/uL n=5 Participants	193 10E3 cells/uL n=7 Participants	125 10E3 cells/uL n=5 Participants	134 10E3 cells/uL n=4 Participants	178 10E3 cells/uL n=21 Participants
ALT	41 u/L n=5 Participants	38 u/L n=7 Participants	59 u/L n=5 Participants	70 u/L n=4 Participants	45 u/L n=21 Participants
APRI	.46 Index n=5 Participants	.45 Index n=7 Participants	1.23 Index n=5 Participants	1.47 Index n=4 Participants	.57 Index n=21 Participants
Estimated GFR	88.36 ml/min/1.73M2 n=5 Participants	86.08 ml/min/1.73M2 n=7 Participants	94.99 ml/min/1.73M2 n=5 Participants	96.61 ml/min/1.73M2 n=4 Participants	90.41 ml/min/1.73M2 n=21 Participants
HIV	5 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	9 Participants n=21 Participants
Albumin	4.10 g/dL n=5 Participants	4.10 g/dL n=7 Participants	4.10 g/dL n=5 Participants	3.90 g/dL n=4 Participants	4.10 g/dL n=21 Participants

PRIMARY outcome

Timeframe: Up to 28 weeks

Population: These analyses were completed on Modified ITT -Genotype Population defined as all treated subjects representing their actual study regimen and who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Arm A: G/P 300 mg/120 mg QD for 12 Wks n=78 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks. Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm B: G/P 300 mg/120 mg QD for 16 Wks n=49 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily Ribavirin 200Mg Tablet: Weight-based 1000-1200 mg	Arm D: G/P 300 mg/120 mg QD for 16 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily
SVR After G/P 12 Wks (Arm A) vs. G/P Given for 16 Weeks (Arm B) to Non-cirrhotic Treatment-experienced GT1 HCV Participants Virologic Response	70 Participants	46 Participants	—	—
SVR After G/P 12 Wks (Arm A) vs. G/P Given for 16 Weeks (Arm B) to Non-cirrhotic Treatment-experienced GT1 HCV Participants Virologic Failure	8 Participants	3 Participants	—	—

PRIMARY outcome

Timeframe: Up to 28 weeks

Population: Cirrhotic subjects achieving Virologic Response at Post-Treatment Week 12

Number of cirrhotic participants who are treatment experienced with a NS5A inhibitor + SOF +/RBV with undetectable HCV RNA 12 weeks after completing G/P plus RBV for 12 wks vs. G/P for 16 Wks

Outcome measures

Outcome measures
Measure	Arm A: G/P 300 mg/120 mg QD for 12 Wks n=21 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks. Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm B: G/P 300 mg/120 mg QD for 16 Wks n=29 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily Ribavirin 200Mg Tablet: Weight-based 1000-1200 mg	Arm D: G/P 300 mg/120 mg QD for 16 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily
Comparison of Cirrhotic Participants Achieving SVR 12 After G/P Plus RBV for 12 Wks vs. G/P for 16 Wks Virologic Response	18 Participants	28 Participants	—	—
Comparison of Cirrhotic Participants Achieving SVR 12 After G/P Plus RBV for 12 Wks vs. G/P for 16 Wks Virologic Failure	3 Participants	1 Participants	—	—

PRIMARY outcome

Timeframe: Up to 16 weeks

Number of subjects who discontinued G/P due to adverse events

Outcome measures

Outcome measures
Measure	Arm A: G/P 300 mg/120 mg QD for 12 Wks n=78 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks. Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm B: G/P 300 mg/120 mg QD for 16 Wks n=49 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks n=21 Participants Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily Ribavirin 200Mg Tablet: Weight-based 1000-1200 mg	Arm D: G/P 300 mg/120 mg QD for 16 Wks n=29 Participants Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily
Tolerability of G/P +/-RBV	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 28 weeks

Population: Analysis was performed the study population "as treated" further defined as mITT-all subjects representing their actual study regimen and who received at least one dose of study drug.

Difference in % of subjects with on-treatment virologic failure further defined as either 1)Breakthrough a)Confirmed HCV RNA ≥ 100 IU/mL after HCV RNA \< Lower Limit of Quantification (LLOQ) at some point during the Treatment Period or confirmed increase from nadir in HCV RNA (two consecutive measurements \> 1 log10 IU/mL above nadir) at any time point during the Treatment Period, or b) a single value indicating viral breakthrough (≥ 100 IU/mL or \> 1 log10 above nadir), followed by patient status of 'Lost to Follow-up', the latter not requiring confirmation by a proximate measurement) or 2) End of Treatment Failure defined as HCV RNA ≥ LLOQ at end of treatment and following at least 6 weeks of treatment.

Outcome measures

Outcome measures
Measure	Arm A: G/P 300 mg/120 mg QD for 12 Wks n=78 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks. Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm B: G/P 300 mg/120 mg QD for 16 Wks n=49 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily Ribavirin 200Mg Tablet: Weight-based 1000-1200 mg	Arm D: G/P 300 mg/120 mg QD for 16 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily
Difference in On-Treatment Virologic Failure Between Arms A & B (Non-cirrhotic Subjects)	1 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: Up to 28 weeks

Population: Analysis performed on any subject with study drug duration of 77 days or greater for Arm A or 105 days or greater for Arm B

Difference in Post-treatment relapse (defined as confirmed HCV RNA\>= Lower limit of quantification (LLOQ) between end of treatment and 12 weeks after the last dose of study drug among subjects who completed treatment as planned with HCV RNA \< LLOQ at end of treatment, excluding subjects with subjects with reinfection)

Outcome measures

Outcome measures
Measure	Arm A: G/P 300 mg/120 mg QD for 12 Wks n=78 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks. Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm B: G/P 300 mg/120 mg QD for 16 Wks n=49 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily Ribavirin 200Mg Tablet: Weight-based 1000-1200 mg	Arm D: G/P 300 mg/120 mg QD for 16 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily
Difference in Relapse Between Arms A & B in Non-cirrhotic Subjects	5 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: Up to 28 weeks

Population: Analysis was performed the study population "as treated" further defined as mITT-all subjects representing their actual study regimen and who received at least one dose of study drug.

Difference in percentage of cirrhotic subjects experiencing on-treatment virologic failure (confirmed increase of \> 1 log10 IU/mL above nadir during treatment, confirmed HCV RNA ≥ 100 IU/mL after HCV RNA \< 15 IU/mL during treatment, or HCV RNA ≥ LLOQ at the end of treatment with at least 6 weeks of treatment) after 12 weeks of G/P with or without RBV for 12 weeks versus 16 weeks of G/P

Outcome measures

Outcome measures
Measure	Arm A: G/P 300 mg/120 mg QD for 12 Wks n=21 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks. Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm B: G/P 300 mg/120 mg QD for 16 Wks n=29 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily Ribavirin 200Mg Tablet: Weight-based 1000-1200 mg	Arm D: G/P 300 mg/120 mg QD for 16 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily
Difference in On-Treatment Virologic Failure Between Arms C and D in Cirrhotic Subjects	2 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Up to 28 weeks

Difference in the percentage of compensated cirrhotic subjects with post-treatment relapse (defined as confirmed HCV RNA\>=Lower limit of quantification (LLOQ) between end of treatment and 12 weeks after last dose of study drug among subjects who completed treatment as planned with HCV RNA\<LLOQ at end of treatment) after receiving 12 weeks G/P +/-Ribavirin (RBV) (Arm C) versus 16 weeks G/P (Arm D)

Outcome measures

Outcome measures
Measure	Arm A: G/P 300 mg/120 mg QD for 12 Wks n=21 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks. Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm B: G/P 300 mg/120 mg QD for 16 Wks n=20 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily Ribavirin 200Mg Tablet: Weight-based 1000-1200 mg	Arm D: G/P 300 mg/120 mg QD for 16 Wks Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily
Difference in % of Relapse Between Cirrhotic Arms C & D	1 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: 28 weeks

Population: Modified Intent to Treat Population (mITT) analysis (All subjects enroll in Main study receiving at least one dose of study drug and according to the treatment arm in which they were actually treated)

Difference in proportions of SVR 12 rates will be determined for 12-week vs. 16-week treatment durations using contrasts within a logistic regression model with cirrhosis status and HCV genotype (1b vs non-1b) as factors

Outcome measures

Outcome measures
Measure	Arm A: G/P 300 mg/120 mg QD for 12 Wks n=78 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks. Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm B: G/P 300 mg/120 mg QD for 16 Wks n=49 Participants Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks n=21 Participants Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily Ribavirin 200Mg Tablet: Weight-based 1000-1200 mg	Arm D: G/P 300 mg/120 mg QD for 16 Wks n=29 Participants Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily
Difference in SVR12 Rates for 12-wk vs 16 wk	70 Participants	46 Participants	18 Participants	28 Participants

Adverse Events

Arm A: G/P 300 mg/120 mg QD for 12 Wks

Serious events: 4 serious events

Other events: 50 other events

Deaths: 1 deaths

Arm B: G/P 300 mg/120 mg QD for 16 Wks

Serious events: 2 serious events

Other events: 32 other events

Deaths: 0 deaths

Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Arm D: G/P 300 mg/120 mg QD for 16 Wks

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm A: G/P 300 mg/120 mg QD for 12 Wks n=78 participants at risk Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks. Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm B: G/P 300 mg/120 mg QD for 16 Wks n=49 participants at risk Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks n=21 participants at risk Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily Ribavirin 200Mg Tablet: Weight-based 1000-1200 mg	Arm D: G/P 300 mg/120 mg QD for 16 Wks n=29 participants at risk Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily
Gastrointestinal disorders Constipation	1.3% 1/78 • Number of events 1 • 142 days	0.00% 0/49 • 142 days	0.00% 0/21 • 142 days	0.00% 0/29 • 142 days
Gastrointestinal disorders Small Intestinal Obstruction	1.3% 1/78 • Number of events 1 • 142 days	0.00% 0/49 • 142 days	0.00% 0/21 • 142 days	0.00% 0/29 • 142 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular Carcinoma	1.3% 1/78 • Number of events 1 • 142 days	0.00% 0/49 • 142 days	0.00% 0/21 • 142 days	0.00% 0/29 • 142 days
Renal and urinary disorders Renal failure chronic	1.3% 1/78 • Number of events 1 • 142 days	0.00% 0/49 • 142 days	0.00% 0/21 • 142 days	0.00% 0/29 • 142 days
Respiratory, thoracic and mediastinal disorders Chronic Obstruction Pulmonary Disease	1.3% 1/78 • Number of events 1 • 142 days	0.00% 0/49 • 142 days	0.00% 0/21 • 142 days	0.00% 0/29 • 142 days
Infections and infestations Sepsis	0.00% 0/78 • 142 days	2.0% 1/49 • Number of events 1 • 142 days	4.8% 1/21 • Number of events 1 • 142 days	0.00% 0/29 • 142 days
Cardiac disorders Acute Myocardial Infarction	0.00% 0/78 • 142 days	2.0% 1/49 • Number of events 1 • 142 days	0.00% 0/21 • 142 days	0.00% 0/29 • 142 days
Renal and urinary disorders Pyelonephritis	0.00% 0/78 • 142 days	2.0% 1/49 • Number of events 1 • 142 days	0.00% 0/21 • 142 days	0.00% 0/29 • 142 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) HCC final outcome Death	1.3% 1/78 • Number of events 1 • 142 days	0.00% 0/49 • 142 days	0.00% 0/21 • 142 days	0.00% 0/29 • 142 days

Other adverse events

Other adverse events
Measure	Arm A: G/P 300 mg/120 mg QD for 12 Wks n=78 participants at risk Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg (3 Glecaprevir/Pibrentasvir (G/P) 100mg/40mg Tablets once-daily by mouth) for 12 weeks. Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm B: G/P 300 mg/120 mg QD for 16 Wks n=49 participants at risk Non-cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once-daily by mouth for 16 weeks (G/P 300 mg/120 mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily	Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks n=21 participants at risk Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Ribavirin 200Mg Tablet (2-3 tablets) twice a day for 12 weeks (G/P 300 mg/120 mg QD + RBV 12 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily Ribavirin 200Mg Tablet: Weight-based 1000-1200 mg	Arm D: G/P 300 mg/120 mg QD for 16 Wks n=29 participants at risk Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks) Glecaprevir/Pibrentasvir (G/P) 300mg/120mg: daily
Infections and infestations Upper Respiratory Tract Infection	6.4% 5/78 • Number of events 5 • 142 days	0.00% 0/49 • 142 days	14.3% 3/21 • Number of events 3 • 142 days	6.9% 2/29 • Number of events 2 • 142 days
General disorders Arthralgia	5.1% 4/78 • Number of events 4 • 142 days	6.1% 3/49 • Number of events 3 • 142 days	9.5% 2/21 • Number of events 2 • 142 days	6.9% 2/29 • Number of events 2 • 142 days
General disorders Fatigue	16.7% 13/78 • Number of events 13 • 142 days	20.4% 10/49 • Number of events 10 • 142 days	47.6% 10/21 • Number of events 10 • 142 days	27.6% 8/29 • Number of events 8 • 142 days
Blood and lymphatic system disorders Anemia	0.00% 0/78 • 142 days	0.00% 0/49 • 142 days	23.8% 5/21 • Number of events 5 • 142 days	0.00% 0/29 • 142 days
Gastrointestinal disorders Nausea	9.0% 7/78 • Number of events 7 • 142 days	14.3% 7/49 • Number of events 7 • 142 days	9.5% 2/21 • Number of events 2 • 142 days	6.9% 2/29 • Number of events 2 • 142 days
Gastrointestinal disorders Abdominal Pain	0.00% 0/78 • 142 days	8.2% 4/49 • Number of events 4 • 142 days	0.00% 0/21 • 142 days	0.00% 0/29 • 142 days
Gastrointestinal disorders Dyspepsia	5.1% 4/78 • Number of events 4 • 142 days	0.00% 0/49 • 142 days	0.00% 0/21 • 142 days	0.00% 0/29 • 142 days
General disorders Influenza like illness	0.00% 0/78 • 142 days	0.00% 0/49 • 142 days	0.00% 0/21 • 142 days	6.9% 2/29 • Number of events 2 • 142 days
Infections and infestations Nasopharyngitis	0.00% 0/78 • 142 days	6.1% 3/49 • Number of events 3 • 142 days	0.00% 0/21 • 142 days	0.00% 0/29 • 142 days
Investigations Weight increased	0.00% 0/78 • 142 days	0.00% 0/49 • 142 days	9.5% 2/21 • Number of events 2 • 142 days	0.00% 0/29 • 142 days
Metabolism and nutrition disorders Decreased Appetite	0.00% 0/78 • 142 days	0.00% 0/49 • 142 days	9.5% 2/21 • Number of events 2 • 142 days	0.00% 0/29 • 142 days
Musculoskeletal and connective tissue disorders Arthralgia	5.1% 4/78 • Number of events 4 • 142 days	8.2% 4/49 • Number of events 4 • 142 days	9.5% 2/21 • Number of events 2 • 142 days	6.9% 2/29 • Number of events 2 • 142 days
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/78 • 142 days	0.00% 0/49 • 142 days	14.3% 3/21 • Number of events 3 • 142 days	0.00% 0/29 • 142 days
Nervous system disorders Headache	19.2% 15/78 • Number of events 17 • 142 days	18.4% 9/49 • Number of events 9 • 142 days	33.3% 7/21 • Number of events 7 • 142 days	20.7% 6/29 • Number of events 7 • 142 days
Nervous system disorders Dizziness	0.00% 0/78 • 142 days	0.00% 0/49 • 142 days	9.5% 2/21 • Number of events 2 • 142 days	0.00% 0/29 • 142 days
Psychiatric disorders Insomnia	0.00% 0/78 • 142 days	6.1% 3/49 • Number of events 3 • 142 days	0.00% 0/21 • 142 days	0.00% 0/29 • 142 days
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/78 • 142 days	0.00% 0/49 • 142 days	9.5% 2/21 • Number of events 2 • 142 days	0.00% 0/29 • 142 days
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/78 • 142 days	0.00% 0/49 • 142 days	0.00% 0/21 • 142 days	10.3% 3/29 • Number of events 3 • 142 days
Gastrointestinal disorders Diarrhea	0.00% 0/78 • 142 days	0.00% 0/49 • 142 days	9.5% 2/21 • Number of events 2 • 142 days	6.9% 2/29 • Number of events 2 • 142 days

Additional Information

Lauren Morelli

UF Hepatology Research at CTRB

Phone: 3522739508

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place