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

February 17, 2020 updated by: University of Florida

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

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.

Study Overview

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 Type

Interventional

Enrollment (Actual)

177

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Palo Alto, California, United States, 94305
        • Stanford University
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • MedStar Health Research Institute
      • Washington, District of Columbia, United States, 20007
        • Georgetown University Hospital
    • Florida
      • Gainesville, Florida, United States, 32610
        • UF Hepatology Research at CTRB
      • Jacksonville, Florida, United States, 32207
        • UF Health Jacksonville-Gastroenterology Emerson
      • Miami, Florida, United States, 33136
        • Schiff Center for Liver Diseases/University of Miami
      • Orlando, Florida, United States, 32803
        • Orlando Immunology Center
    • Georgia
      • Atlanta, Georgia, United States, 303012
        • Atlanta Medical Center
      • Atlanta, Georgia, United States, 30308
        • Atlanta Gastro Associates
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • The Johns Hopkins Hospital/John G. Bartlett Specialty Practice
      • Catonsville, Maryland, United States, 21228
        • Digestive Disease Associates, PA
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-5601
        • University of Michigan
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Univ. of Minnesota Health Clinics and Surgery Center, Inc.
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • Southern Therapy and Advanced Research
    • New York
      • Manhasset, New York, United States, 11030
        • Northwell Health - Sandra Atlaas Bass Center for Liver Diseases
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10016
        • NYU Langone Medical Center
      • New York, New York, United States, 10021
        • Weill Cornell Medicine, Hepatology
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • INTEGRIS Baptist Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania-Perelman Center for Advanced Medicine
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Virginia
      • Richmond, Virginia, United States, 23226
        • Bon Secours Liver Institute of Virginia
      • Richmond, Virginia, United States, 23298-0341
        • Virginia Commonwealth University
    • Washington
      • Seattle, Washington, United States, 98101
        • Virginia Mason Medical Center
      • Seattle, Washington, United States, 98104
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
daily
Other Names:
  • Glecaprevir/Pibrentasvir
  • GLE/PIB (Glecaprevir/Pibrentasvir)
Experimental: 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)
daily
Other Names:
  • Glecaprevir/Pibrentasvir
  • GLE/PIB (Glecaprevir/Pibrentasvir)
Experimental: 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)
daily
Other Names:
  • Glecaprevir/Pibrentasvir
  • GLE/PIB (Glecaprevir/Pibrentasvir)
Weight-based 1000-1200 mg
Other Names:
  • Ribasphere 200Mg Tablet
Experimental: 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)
daily
Other Names:
  • Glecaprevir/Pibrentasvir
  • GLE/PIB (Glecaprevir/Pibrentasvir)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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)
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
Time Frame: 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
Up to 28 weeks
Tolerability of G/P +/-RBV
Time Frame: Up to 16 weeks
Number of subjects who discontinued G/P due to adverse events
Up to 16 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: David R Nelson, MD, University of Florida

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 20, 2017

Primary Completion (Actual)

December 28, 2018

Study Completion (Actual)

February 6, 2020

Study Registration Dates

First Submitted

March 21, 2017

First Submitted That Met QC Criteria

March 21, 2017

First Posted (Actual)

March 27, 2017

Study Record Updates

Last Update Posted (Actual)

February 26, 2020

Last Update Submitted That Met QC Criteria

February 17, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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