Back to resultsMulti-Center, Randomized, Open-Label Study of G/P +/- RBV for NS5A + SOF Previously Treated GT1 HCV Subjects
Primary Purpose
Hepatitis C, HCV
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Glecaprevir/Pibrentasvir (G/P) 300mg/120mg
Ribavirin 200Mg Tablet
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C focused on measuring HCV, Previously treated
Eligibility Criteria
Inclusion Criteria:
- Male or female at least 18 years of age at time of screening.
- A history of previous treatment with an NS5A-inhibitor plus sofosbuvir therapy ± RBV for chronic HCV genotype 1 infection.
- Treatment must have been completed at least 1 month prior to Screening Visit.
- 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:
- History of severe, life-threatening or other significant sensitivity to any drug.
- 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.
- 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.
- 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.
- HCV genotype performed during screening indicating co-infection with more than one HCV genotype.
- History or presence of liver decompensation.
Sites / Locations
- Stanford University
- University of California, San Francisco
- Georgetown University Hospital
- MedStar Health Research Institute
- UF Hepatology Research at CTRB
- UF Health Jacksonville-Gastroenterology Emerson
- Schiff Center for Liver Diseases/University of Miami
- Orlando Immunology Center
- Atlanta Medical Center
- Atlanta Gastro Associates
- Rush University Medical Center
- The Johns Hopkins Hospital/John G. Bartlett Specialty Practice
- Digestive Disease Associates, PA
- Massachusetts General Hospital
- University of Michigan
- Univ. of Minnesota Health Clinics and Surgery Center, Inc.
- Southern Therapy and Advanced Research
- Northwell Health - Sandra Atlaas Bass Center for Liver Diseases
- NYU Langone Medical Center
- Weill Cornell Medicine, Hepatology
- Columbia University Medical Center
- University of North Carolina at Chapel Hill
- Duke University Medical Center
- The Ohio State University
- Integris Baptist Medical Center
- University of Pennsylvania-Perelman Center for Advanced Medicine
- Medical University of South Carolina
- Bon Secours Liver Institute of Virginia
- Virginia Commonwealth University
- Virginia Mason Medical Center
- University of Washington
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Arm A: G/P 300 mg/120 mg QD for 12 Wks
Arm B: G/P 300 mg/120 mg QD for 16 Wks
Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks
Arm D: G/P 300 mg/120 mg QD for 16 Wks
Arm Description
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.
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)
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)
Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks)
Outcomes
Primary Outcome Measures
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 <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
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
Number of subjects who discontinued G/P due to adverse events
Secondary Outcome Measures
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.
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)
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
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<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
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
Full Information
NCT ID
NCT03092375
First Posted
March 21, 2017
Last Updated
February 17, 2020
Sponsor
University of Florida
Collaborators
University of North Carolina, Chapel Hill, AbbVie
1. Study Identification
Unique Protocol Identification Number
NCT03092375
Brief Title
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
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
April 20, 2017 (Actual)
Primary Completion Date
December 28, 2018 (Actual)
Study Completion Date
February 6, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
Collaborators
University of North Carolina, Chapel Hill, AbbVie
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, HCV
Keywords
HCV, Previously treated
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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:
Arm A: G/P 300 mg/120 mg Once a day for 12 weeks
Arm B: G/P 300 mg/120mg Once a day for 16 weeks
Subjects with compensated cirrhosis will be randomized 1:1 to:
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
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
177 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: G/P 300 mg/120 mg QD for 12 Wks
Arm Type
Experimental
Arm Description
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 Title
Arm B: G/P 300 mg/120 mg QD for 16 Wks
Arm Type
Experimental
Arm Description
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 Title
Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks
Arm Type
Experimental
Arm Description
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 Title
Arm D: G/P 300 mg/120 mg QD for 16 Wks
Arm Type
Experimental
Arm Description
Cirrhotic subjects will take Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily for 16 weeks (G/P 300 mg/120mg QD for 16 Wks)
Intervention Type
Drug
Intervention Name(s)
Glecaprevir/Pibrentasvir (G/P) 300mg/120mg
Other Intervention Name(s)
Glecaprevir/Pibrentasvir, GLE/PIB (Glecaprevir/Pibrentasvir)
Intervention Description
daily
Intervention Type
Drug
Intervention Name(s)
Ribavirin 200Mg Tablet
Other Intervention Name(s)
Ribasphere 200Mg Tablet
Intervention Description
Weight-based 1000-1200 mg
Primary Outcome Measure Information:
Title
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
Description
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)
Time Frame
Up to 28 weeks
Title
Comparison of Cirrhotic Participants Achieving SVR 12 After G/P Plus RBV for 12 Wks vs. G/P for 16 Wks
Description
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
Time Frame
Up to 28 weeks
Title
Tolerability of G/P +/-RBV
Description
Number of subjects who discontinued G/P due to adverse events
Time Frame
Up to 16 weeks
Secondary Outcome Measure Information:
Title
Difference in On-Treatment Virologic Failure Between Arms A & B (Non-cirrhotic Subjects)
Description
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.
Time Frame
Up to 28 weeks
Title
Difference in Relapse Between Arms A & B in Non-cirrhotic Subjects
Description
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)
Time Frame
Up to 28 weeks
Title
Difference in On-Treatment Virologic Failure Between Arms C and D in Cirrhotic Subjects
Description
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
Time Frame
Up to 28 weeks
Title
Difference in % of Relapse Between Cirrhotic Arms C & D
Description
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)
Time Frame
Up to 28 weeks
Title
Difference in SVR12 Rates for 12-wk vs 16 wk
Description
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
Time Frame
28 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female at least 18 years of age at time of screening.
A history of previous treatment with an NS5A-inhibitor plus sofosbuvir therapy ± RBV for chronic HCV genotype 1 infection.
Treatment must have been completed at least 1 month prior to Screening Visit.
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:
History of severe, life-threatening or other significant sensitivity to any drug.
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.
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.
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.
HCV genotype performed during screening indicating co-infection with more than one HCV genotype.
History or presence of liver decompensation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David R Nelson, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
MedStar Health Research Institute
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
UF Hepatology Research at CTRB
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
UF Health Jacksonville-Gastroenterology Emerson
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Schiff Center for Liver Diseases/University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Orlando Immunology Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Atlanta Medical Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
303012
Country
United States
Facility Name
Atlanta Gastro Associates
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
The Johns Hopkins Hospital/John G. Bartlett Specialty Practice
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Digestive Disease Associates, PA
City
Catonsville
State/Province
Maryland
ZIP/Postal Code
21228
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-5601
Country
United States
Facility Name
Univ. of Minnesota Health Clinics and Surgery Center, Inc.
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Southern Therapy and Advanced Research
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Northwell Health - Sandra Atlaas Bass Center for Liver Diseases
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
NYU Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Weill Cornell Medicine, Hepatology
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Integris Baptist Medical Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
University of Pennsylvania-Perelman Center for Advanced Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Bon Secours Liver Institute of Virginia
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23226
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0341
Country
United States
Facility Name
Virginia Mason Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98101
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34023351
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.
Results Reference
derived
PubMed Identifier
31401140
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.
Results Reference
derived
Learn more about this trial
Multi-Center, Randomized, Open-Label Study of G/P +/- RBV for NS5A + SOF Previously Treated GT1 HCV Subjects
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