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

Hepatitis C Clinical Trial

Official title:

A Phase 3b, Multi-Center, Randomized, Open-Label, Pragmatic Study of Glecaprevir/Pibrentasvir (G/P) +/- Ribavirin for GT1 Subjects With Chronic Hepatitis C Previously Treated With an NS5A Inhibitor + Sofosbuvir Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03092375
• Other study ID #: B16-439
• Secondary ID: OCR16260
• Status: Completed
• Phase: Phase 3
• Start date: April 20, 2017
• Est. completion date: February 6, 2020

Study information

• Verified date: February 2020
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 177
• Est. completion date: February 6, 2020
• Est. primary completion date: December 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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.

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.

Related Conditions & MeSH terms

• HCV
• Hepatitis
• Hepatitis C

Intervention

Drug:
• Glecaprevir/Pibrentasvir (G/P) 300mg/120mg
daily
• Ribavirin 200Mg Tablet
Weight-based 1000-1200 mg

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Atlanta Gastro Associates	Atlanta	Georgia
United States	Atlanta Medical Center	Atlanta	Georgia
United States	The Johns Hopkins Hospital/John G. Bartlett Specialty Practice	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Digestive Disease Associates, PA	Catonsville	Maryland
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	The Ohio State University	Columbus	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	UF Hepatology Research at CTRB	Gainesville	Florida
United States	Southern Therapy and Advanced Research	Jackson	Mississippi
United States	UF Health Jacksonville-Gastroenterology Emerson	Jacksonville	Florida
United States	Northwell Health - Sandra Atlaas Bass Center for Liver Diseases	Manhasset	New York
United States	Schiff Center for Liver Diseases/University of Miami	Miami	Florida
United States	Univ. of Minnesota Health Clinics and Surgery Center, Inc.	Minneapolis	Minnesota
United States	Columbia University Medical Center	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	Weill Cornell Medicine, Hepatology	New York	New York
United States	Integris Baptist Medical Center	Oklahoma City	Oklahoma
United States	Orlando Immunology Center	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	University of Pennsylvania-Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Bon Secours Liver Institute of Virginia	Richmond	Virginia
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Health Research Institute	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
University of Florida	AbbVie, University of North Carolina, Chapel Hill

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up to 28 weeks
Primary	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	Up to 28 weeks
Primary	Tolerability of G/P +/-RBV	Number of subjects who discontinued G/P due to adverse events	Up to 16 weeks
Secondary	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.	Up to 28 weeks
Secondary	Difference in Relapse Between Arms A & B in Non-cirrhotic Subjects	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)	Up to 28 weeks
Secondary	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	Up to 28 weeks
Secondary	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	Up to 28 weeks
Secondary	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	28 weeks