Clinical trial NCT03092375: Multi-Center, Randomized, Open-Label Study of G/P +/- RBV for NS5A + SOF Previously Treated GT1 HCV Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C
HCV
Keywords: HCV
Previously treated
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: University of North Carolina, Chapel Hill
name: AbbVie
First posted: 2017-03-27
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Main Study Up to 225 subjects will be enrolled into 4 study arms A, B, C and D with Glecaprevir/Pibrentasvir (G/P) with or without Ribavirin (RBV).

About 75-90 non-cirrhotic subjects will be randomized in a 2:1 ratio to Arms A and B, and about 110-135 compensated cirrhotic subjects will be randomized in a 1:1 ratio to Arms C and D.

Non-cirrhotic subjects will be randomized 2:1 to:

1. Arm A: G/P 300 mg/120 mg Once a day for 12 weeks
2. Arm B: G/P 300 mg/120mg Once a day for 16 weeks

   Subjects with compensated cirrhosis will be randomized 1:1 to:
3. Arm C: G/P 300 mg/120 mg QD + weight-based RBV (Ribavirin) Twice a day (1000 mg or 1200 mg total daily dose) for 12 weeks
4. Arm D: G/P 300 mg/120 mg QD for 16 weeks Retreatment sub-study Up to 11 subjects who still have hepatitis C virus after being treated in the Main study will have the option to enter the Retreatment sub-study and receive G/P plus Sofosbuvir and with or without RBV.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Up to 28 weeks
measure: Comparison of Cirrhotic Participants Achieving SVR 12 After G/P Plus RBV for 12 Wks vs. G/P for 16 Wks
timeFrame: Up to 28 weeks
measure: Tolerability of G/P +/-RBV
timeFrame: Up to 16 weeks
Secondary outcomes:
measure: Difference in On-Treatment Virologic Failure Between Arms A & B (Non-cirrhotic Subjects)
timeFrame: Up to 28 weeks
measure: Difference in Relapse Between Arms A & B in Non-cirrhotic Subjects
timeFrame: Up to 28 weeks
measure: Difference in On-Treatment Virologic Failure Between Arms C and D in Cirrhotic Subjects
timeFrame: Up to 28 weeks
measure: Difference in % of Relapse Between Cirrhotic Arms C & D
timeFrame: Up to 28 weeks
measure: Difference in SVR12 Rates for 12-wk vs 16 wk
timeFrame: 28 weeks
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: MedStar Health Research Institute
state: District of Columbia
city: Gainesville
country: United States
facility: UF Hepatology Research at CTRB
state: Florida
city: Jacksonville
country: United States
facility: UF Health Jacksonville-Gastroenterology Emerson
state: Florida
city: Miami
country: United States
facility: Schiff Center for Liver Diseases/University of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Medical Center
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Gastro Associates
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital/John G. Bartlett Specialty Practice
state: Maryland
city: Catonsville
country: United States
facility: Digestive Disease Associates, PA
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Univ. of Minnesota Health Clinics and Surgery Center, Inc.
state: Minnesota
city: Jackson
country: United States
facility: Southern Therapy and Advanced Research
state: Mississippi
city: Manhasset
country: United States
facility: Northwell Health - Sandra Atlaas Bass Center for Liver Diseases
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine, Hepatology
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania-Perelman Center for Advanced Medicine
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Richmond
country: United States
facility: Bon Secours Liver Institute of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Florida
name: David R Nelson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang GP, Schnell GL, Kort JJ, Sidhu GS, Schuster L, Tripathi RL, Larsen L, Michael LC, Bergquist K, Magee A, Patel CB, Whitlock JA, Tamashiro R, Peter JA, Fried MW, Nelson DR. Linkage of resistance-associated substitutions in GT1 sofosbuvir + NS5A inhibitor failures treated with glecaprevir/pibrentasvir. J Hepatol. 2021 Oct;75(4):820-828. doi: 10.1016/j.jhep.2021.04.057. Epub 2021 May 21.
citation: Lok AS, Sulkowski MS, Kort JJ, Willner I, Reddy KR, Shiffman ML, Hassan MA, Pearlman BL, Hinestrosa F, Jacobson IM, Morelli G, Peter JA, Vainorius M, Michael LC, Fried MW, Wang GP, Lu W, Larsen L, Nelson DR. Efficacy of Glecaprevir and Pibrentasvir in Patients With Genotype 1 Hepatitis C Virus Infection With Treatment Failure After NS5A Inhibitor Plus Sofosbuvir Therapy. Gastroenterology. 2019 Dec;157(6):1506-1517.e1. doi: 10.1053/j.gastro.2019.08.008. Epub 2019 Aug 8.