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

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ClinicalTrials.gov Identifier: NCT03092375
Recruitment Status : Enrolling by invitation
First Posted : March 27, 2017
Last Update Posted : December 3, 2018
Sponsor:
Collaborators:
University of North Carolina, Chapel Hill
AbbVie
Information provided by (Responsible Party):
University of Florida

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.

Condition or disease Intervention/treatment Phase
Hepatitis C HCV Drug: Glecaprevir/Pibrentasvir (G/P) 300mg/120mg Drug: Ribavirin 200Mg Tablet Drug: Sofosbuvir 400Mg Tab Phase 3

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  (Clinical Trial)
Actual Enrollment : 215 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 20, 2017
Estimated Primary Completion Date : January 1, 2019
Estimated Study Completion Date : August 31, 2019

Resource links provided by the National Library of Medicine


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.
Drug: Glecaprevir/Pibrentasvir (G/P) 300mg/120mg
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)
Drug: Glecaprevir/Pibrentasvir (G/P) 300mg/120mg
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)
Drug: Glecaprevir/Pibrentasvir (G/P) 300mg/120mg
daily
Other Names:
  • Glecaprevir/Pibrentasvir
  • GLE/PIB (Glecaprevir/Pibrentasvir)

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

Experimental: Retreatment sub-study
Subjects who experience virologic failure (HCV RNA positive after treatment in Main Study) will receive Glecaprevir/Pibrentasvir (G/P) 300mg/120mg once daily plus Sofosbuvir 400Mg Tab with or without Ribavirin 200Mg (RBV)
Drug: Glecaprevir/Pibrentasvir (G/P) 300mg/120mg
daily
Other Names:
  • Glecaprevir/Pibrentasvir
  • GLE/PIB (Glecaprevir/Pibrentasvir)

Drug: Ribavirin 200Mg Tablet
Weight-based 1000-1200 mg
Other Name: Ribasphere 200Mg Tablet

Drug: Sofosbuvir 400Mg Tab
Daily
Other Name: Sovaldi




Primary Outcome Measures :
  1. Compare percentage of non-cirrhotic participants achieving SVR 12 (Sustained Virologic Response at 12 weeks post treatment) after G/P 12 wks vs. G/P given for 16 weeks in non-cirrhotic tx-experienced GT1 HCV subjects [ Time Frame: Up to 28 weeks ]
    Percentage of participants with undetectable HCV RNA 12 weeks after completing 12 or 16 weeks of G/P will be compared

  2. Compare percentage 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 ]
    Percentage of participants with undetectable HCV RNA 12 weeks after completing 12 or 16 weeks of G/P will be compared


Secondary Outcome Measures :
  1. Difference in efficacy (SVR 12) of G/P +/- RBV for 12 weeks (Arms A + C) versus G/P for 16 weeks (Arms B + D) [ Time Frame: Up to 28 weeks ]
    Percentage of subjects with undetectable HCV RNA 12 weeks after treatment

  2. Difference in percentages of subjects with on-treatment virologic failure between 4 arms [ Time Frame: Up to 16 weeks ]
    Percentage of subjects with detectable HCV RNA during treatment in Arm A will be compared to Arm B and Arm C will be compared to Arm D

  3. Difference in percentages of subjects with post-treatment relapse between arms [ Time Frame: Up to 28 weeks ]
    Percentages of subjects with detectable HCV RNA following undetectable HCV RNA in Arm A vs. Arm B and Arm C vs. Arm D



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03092375


  Show 31 Study Locations
Sponsors and Collaborators
University of Florida
University of North Carolina, Chapel Hill
AbbVie
Investigators
Principal Investigator: David R Nelson, MD University of Florida

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT03092375     History of Changes
Other Study ID Numbers: B16-439
First Posted: March 27, 2017    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Florida:
HCV
Previously treated

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Ribavirin
Sofosbuvir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents