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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 : Completed
First Posted : March 27, 2017
Results First Posted : February 5, 2020
Last Update Posted : February 26, 2020
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 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 177 participants
Allocation: Randomized
Intervention Model: Parallel 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
Actual Primary Completion Date : December 28, 2018
Actual Study Completion Date : February 6, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Ribavirin

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)




Primary Outcome Measures :
  1. 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)

  2. 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

  3. Tolerability of G/P +/-RBV [ Time Frame: Up to 16 weeks ]
    Number of subjects who discontinued G/P due to adverse events


Secondary Outcome Measures :
  1. 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.

  2. 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)

  3. 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

  4. 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)

  5. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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


Locations
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Sponsors and Collaborators
University of Florida
University of North Carolina, Chapel Hill
AbbVie
Investigators
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Principal Investigator: David R Nelson, MD University of Florida
  Study Documents (Full-Text)

Documents provided by University of Florida:
Study Protocol  [PDF] November 20, 2018
Statistical Analysis Plan  [PDF] March 8, 2019

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT03092375    
Other Study ID Numbers: B16-439
OCR16260 ( Other Identifier: University of Florida )
First Posted: March 27, 2017    Key Record Dates
Results First Posted: February 5, 2020
Last Update Posted: February 26, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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