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

NCT03092375 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: B16-439OCR16260
• Study Type: interventional
• Target: 177
• Locations: 1 country
• Sites: 31

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.

Conditions

Hepatitis C; HCV

Keywords

HCV; Previously treated

Outcome Measures

Primary Outcomes (3)

• 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)

  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

  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

  Number of subjects who discontinued G/P due to adverse events

  Up to 16 weeks

Secondary Outcomes (5)

• Difference in On-Treatment Virologic Failure Between Arms A & B (Non-cirrhotic Subjects)

  Up to 28 weeks

• Difference in Relapse Between Arms A & B in Non-cirrhotic Subjects

  Up to 28 weeks

• Difference in On-Treatment Virologic Failure Between Arms C and D in Cirrhotic Subjects

  Up to 28 weeks

• Difference in % of Relapse Between Cirrhotic Arms C & D

  Up to 28 weeks

• Difference in SVR12 Rates for 12-wk vs 16 wk

  28 weeks

Study Arms (4)

Arm A: G/P 300 mg/120 mg QD for 12 Wks

EXPERIMENTAL

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

Arm B: G/P 300 mg/120 mg QD for 16 Wks

EXPERIMENTAL

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

Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks

EXPERIMENTAL

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; Drug: Ribavirin 200Mg Tablet

Arm D: G/P 300 mg/120 mg QD for 16 Wks

EXPERIMENTAL

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

Interventions

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

daily

Also known as: Glecaprevir/Pibrentasvir, GLE/PIB (Glecaprevir/Pibrentasvir)

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

Ribavirin 200Mg Tablet DRUG

Weight-based 1000-1200 mg

Also known as: Ribasphere 200Mg Tablet

Arm C: G/P 300 mg/120 mg QD + RBV 12 Wks

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Florida: lead
• University of North Carolina, Chapel Hill: collaborator
• AbbVie: collaborator

Study Sites (31)

Stanford University

Palo Alto, California, 94305, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

MedStar Health Research Institute

Washington D.C., District of Columbia, 20010, United States

Location

UF Hepatology Research at CTRB

Gainesville, Florida, 32610, United States

Location

UF Health Jacksonville-Gastroenterology Emerson

Jacksonville, Florida, 32207, United States

Location

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, 33136, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Atlanta Medical Center

Atlanta, Georgia, 303012, United States

Location

Atlanta Gastro Associates

Atlanta, Georgia, 30308, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

The Johns Hopkins Hospital/John G. Bartlett Specialty Practice

Baltimore, Maryland, 21287, United States

Location

Digestive Disease Associates, PA

Catonsville, Maryland, 21228, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-5601, United States

Location

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

Minneapolis, Minnesota, 55455, United States

Location

Southern Therapy and Advanced Research

Jackson, Mississippi, 39216, United States

Location

Northwell Health - Sandra Atlaas Bass Center for Liver Diseases

Manhasset, New York, 11030, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Weill Cornell Medicine, Hepatology

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Integris Baptist Medical Center

Oklahoma City, Oklahoma, 73112, United States

Location

University of Pennsylvania-Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Bon Secours Liver Institute of Virginia

Richmond, Virginia, 23226, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298-0341, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

University of Washington

Seattle, Washington, 98104, United States

Location

Related Publications (2)

• 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.

  PMID: 34023351 DERIVED

• 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.

  PMID: 31401140 DERIVED

MeSH Terms

Conditions

Hepatitis C

Interventions

glecaprevir; pibrentasvir; glecaprevir and pibrentasvir; Ribavirin; Tablets

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dosage Forms; Pharmaceutical Preparations

Limitations and Caveats

This study did not include a group that received 16 weeks of glecaprevir and pibrentasvir with ribavirin.

Results Point of Contact

• Title: Lauren Morelli
• Organization: UF Hepatology Research at CTRB

LAUREN.MORELLI@MEDICINE.UFL.EDU

3522739508

Study Officials

• David R Nelson, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 21, 2017
• First Posted: March 27, 2017
• Study Start: April 20, 2017
• Primary Completion: December 28, 2018
• Study Completion: February 6, 2020
• Last Updated: February 26, 2020
• Results First Posted: February 5, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (31)