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

NCT ID: NCT03092375

Last Updated: 2020-02-26

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

177 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-04-20

Study Completion Date

2020-02-06

Brief Summary

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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

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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.

Conditions

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Hepatitis C HCV

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Glecaprevir/Pibrentasvir (G/P) 300mg/120mg

Intervention Type DRUG

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)

Group Type EXPERIMENTAL

Glecaprevir/Pibrentasvir (G/P) 300mg/120mg

Intervention Type DRUG

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)

Group Type EXPERIMENTAL

Glecaprevir/Pibrentasvir (G/P) 300mg/120mg

Intervention Type DRUG

daily

Ribavirin 200Mg Tablet

Intervention Type DRUG

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)

Group Type EXPERIMENTAL

Glecaprevir/Pibrentasvir (G/P) 300mg/120mg

Intervention Type DRUG

daily

Interventions

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Glecaprevir/Pibrentasvir (G/P) 300mg/120mg

daily

Intervention Type DRUG

Ribavirin 200Mg Tablet

Weight-based 1000-1200 mg

Intervention Type DRUG

Other Intervention Names

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Glecaprevir/Pibrentasvir GLE/PIB (Glecaprevir/Pibrentasvir) Ribasphere 200Mg Tablet

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of North Carolina, Chapel Hill

OTHER

Sponsor Role collaborator

AbbVie

INDUSTRY

Sponsor Role collaborator

University of Florida

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David R Nelson, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

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Stanford University

Palo Alto, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

MedStar Health Research Institute

Washington D.C., District of Columbia, United States

Site Status

UF Hepatology Research at CTRB

Gainesville, Florida, United States

Site Status

UF Health Jacksonville-Gastroenterology Emerson

Jacksonville, Florida, United States

Site Status

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, United States

Site Status

Orlando Immunology Center

Orlando, Florida, United States

Site Status

Atlanta Medical Center

Atlanta, Georgia, United States

Site Status

Atlanta Gastro Associates

Atlanta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

The Johns Hopkins Hospital/John G. Bartlett Specialty Practice

Baltimore, Maryland, United States

Site Status

Digestive Disease Associates, PA

Catonsville, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Univ. of Minnesota Health Clinics and Surgery Center, Inc.

Minneapolis, Minnesota, United States

Site Status

Southern Therapy and Advanced Research

Jackson, Mississippi, United States

Site Status

Northwell Health - Sandra Atlaas Bass Center for Liver Diseases

Manhasset, New York, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

Weill Cornell Medicine, Hepatology

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Integris Baptist Medical Center

Oklahoma City, Oklahoma, United States

Site Status

University of Pennsylvania-Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Bon Secours Liver Institute of Virginia

Richmond, Virginia, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Virginia Mason Medical Center

Seattle, Washington, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 34023351 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31401140 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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OCR16260

Identifier Type: OTHER

Identifier Source: secondary_id

B16-439

Identifier Type: -

Identifier Source: org_study_id

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