The study will enroll well-compensated cirrhotic as well as non-cirrhotic subjects treatment experienced with an NS5a Inhibitor + sofosbuvir and will include patients who did not complete the prescribed duration due to adverse event or any reason other than for non/poor compliance. Subjects will be randomized to 12 or 16 weeks of treatment.
The primary purpose of this study is to compare the efficacy and safety of glecaprevir and pibrentasvir (G/P) for 12 weeks to G/P for 16 weeks in non-cirrhotic NS5A (non-structural protein 5a)-inhibitor plus sofosbuvir ± RBV (Ribavirin) treatment-experienced adults with HCV genotype 1 (GT1) infection, and to compare the efficacy and safety of G/P with RBV for 12 weeks to G/P without RBV for 16 weeks in NS5A-inhibitor plus sofosbuvir (SOF) ± RBV treatment-experienced adults with compensated cirrhosis and GT1 infection.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
177
Weight-based 1000-1200 mg
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
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)
Time frame: Up to 28 weeks
Comparison of Cirrhotic Participants Achieving SVR 12 After G/P Plus RBV for 12 Wks vs. G/P for 16 Wks
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
Time frame: Up to 28 weeks
Tolerability of G/P +/-RBV
Number of subjects who discontinued G/P due to adverse events
Time frame: Up to 16 weeks
Difference in On-Treatment Virologic Failure Between Arms A & B (Non-cirrhotic Subjects)
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.
Time frame: Up to 28 weeks
Difference in Relapse Between Arms A & B in Non-cirrhotic Subjects
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Stanford University
Palo Alto, California, United States
University of California, San Francisco
San Francisco, California, United States
Georgetown University Hospital
Washington D.C., District of Columbia, United States
MedStar Health Research Institute
Washington D.C., District of Columbia, United States
UF Hepatology Research at CTRB
Gainesville, Florida, United States
UF Health Jacksonville-Gastroenterology Emerson
Jacksonville, Florida, United States
Schiff Center for Liver Diseases/University of Miami
Miami, Florida, United States
Orlando Immunology Center
Orlando, Florida, United States
Atlanta Medical Center
Atlanta, Georgia, United States
Atlanta Gastro Associates
Atlanta, Georgia, United States
...and 21 more locations
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)
Time frame: Up to 28 weeks
Difference in On-Treatment Virologic Failure Between Arms C and D in Cirrhotic Subjects
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
Time frame: Up to 28 weeks
Difference in % of Relapse Between Cirrhotic Arms C & D
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)
Time frame: Up to 28 weeks
Difference in SVR12 Rates for 12-wk vs 16 wk
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
Time frame: 28 weeks