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

Phase 3

Completed

• Conditions: HCV; Hepatitis C
• Interventions: Drug: Glecaprevir/Pibrentasvir (G/P) 300mg/120mg; Drug: Ribavirin 200Mg Tablet

• Registration Number: NCT03092375
• Lead Sponsor: University of Florida

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2017-03-21
• Study First Submitted QC: 2017-03-21
• Study First Posted: 2017-03-27
• Study Start: 2017-04-20
• Primary Completion: 2018-12-28
• Results First Submitted: 2019-12-18
• Results First Submitted QC: 2020-01-21
• Status Verified: 2020-02
• Results First Posted: 2020-02-05
• Study Completion: 2020-02-06
• Last Update Submitted: 2020-02-17
• Last Update Posted: 2020-02-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 177

Inclusion Criteria

1. Male or female at least 18 years of age at time of screening.
2. A history of previous treatment with an NS5A-inhibitor plus sofosbuvir therapy ± RBV for chronic HCV genotype 1 infection.
3. Treatment must have been completed at least 1 month prior to Screening Visit.
4. Screening laboratory result indicating chronic HCV GT1 infection. Subjects must be able to understand and adhere to the study visit schedule and all other protocol requirements and must voluntarily sign and date an informed consent.

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Exclusion Criteria

1. History of severe, life-threatening or other significant sensitivity to any drug.
2. Female who is pregnant, planning to become pregnant during the study or breastfeeding; or male whose partner is pregnant or planning to become pregnant during the study.
3. Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol in the opinion of the investigator.
4. Positive test result at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab) in patient without known history of HIV infection.
5. HCV genotype performed during screening indicating co-infection with more than one HCV genotype.
6. History or presence of liver decompensation.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: G/P 300 mg/120 mg QD for 12 Wks	Glecaprevir/Pibrentasvir (G/P) 300mg/120mg	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.
Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks	Ribavirin 200Mg Tablet	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)
Arm B: G/P 300 mg/120 mg QD for 16 Wks	Glecaprevir/Pibrentasvir (G/P) 300mg/120mg	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)
Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks	Glecaprevir/Pibrentasvir (G/P) 300mg/120mg	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)
Arm D: G/P 300 mg/120 mg QD for 16 Wks	Glecaprevir/Pibrentasvir (G/P) 300mg/120mg	Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks)

Primary Outcome Measures

Name	Time	Method
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	Up to 28 weeks	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)
Comparison of Cirrhotic Participants Achieving SVR 12 After G/P Plus RBV for 12 Wks vs. G/P for 16 Wks	Up to 28 weeks	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
Tolerability of G/P +/-RBV	Up to 16 weeks	Number of subjects who discontinued G/P due to adverse events

Secondary Outcome Measures

Name	Time	Method
Difference in Relapse Between Arms A & B in Non-cirrhotic Subjects	Up to 28 weeks	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)
Difference in On-Treatment Virologic Failure Between Arms C and D in Cirrhotic Subjects	Up to 28 weeks	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
Difference in % of Relapse Between Cirrhotic Arms C & D	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)
Difference in SVR12 Rates for 12-wk vs 16 wk	28 weeks	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
Difference in On-Treatment Virologic Failure Between Arms A & B (Non-cirrhotic Subjects)	Up to 28 weeks	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.

Trial Locations

Locations (31)

MedStar Health Research Institute; 🇺🇸 Washington, District of Columbia, United States

UF Hepatology Research at CTRB; 🇺🇸 Gainesville, Florida, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

The Johns Hopkins Hospital/John G. Bartlett Specialty Practice; 🇺🇸 Baltimore, Maryland, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Northwell Health - Sandra Atlaas Bass Center for Liver Diseases; 🇺🇸 Manhasset, New York, United States

University of Pennsylvania-Perelman Center for Advanced Medicine; 🇺🇸 Philadelphia, Pennsylvania, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Univ. of Minnesota Health Clinics and Surgery Center, Inc.; 🇺🇸 Minneapolis, Minnesota, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

Georgetown University Hospital; 🇺🇸 Washington, District of Columbia, United States

Schiff Center for Liver Diseases/University of Miami; 🇺🇸 Miami, Florida, United States

UF Health Jacksonville-Gastroenterology Emerson; 🇺🇸 Jacksonville, Florida, United States

Atlanta Medical Center; 🇺🇸 Atlanta, Georgia, United States

Orlando Immunology Center; 🇺🇸 Orlando, Florida, United States

Atlanta Gastro Associates; 🇺🇸 Atlanta, Georgia, United States

Digestive Disease Associates, PA; 🇺🇸 Catonsville, Maryland, United States

Southern Therapy and Advanced Research; 🇺🇸 Jackson, Mississippi, United States

NYU Langone Medical Center; 🇺🇸 New York, New York, United States

Weill Cornell Medicine, Hepatology; 🇺🇸 New York, New York, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Integris Baptist Medical Center; 🇺🇸 Oklahoma City, Oklahoma, United States

The Ohio State University; 🇺🇸 Columbus, Ohio, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

Bon Secours Liver Institute of Virginia; 🇺🇸 Richmond, Virginia, United States

Virginia Mason Medical Center; 🇺🇸 Seattle, Washington, United States

University of Washington; 🇺🇸 Seattle, Washington, United States