Evaluate the Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed-Dose Combination and Ribavirin for 12 Weeks in Participants With Chronic HCV Infection and Child-Pugh-Turcotte Class C Cirrhosis

A Phase 2, Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed-Dose Combination and Ribavirin for 12 Weeks in Subjects With Chronic HCV Infection and Child-Pugh-Turcotte Class C Cirrhosis

The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of the treatment with sofosbuvir velpatasvir (SOF/VEL) fixed-dose combination (FDC) with ribavirin (RBV) for 12 weeks in participants with chronic hepatitis C virus (HCV) infection and Child-Pugh-Turcotte (CPT) Class C cirrhosis.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus Infection
• Intervention / Treatment: Drug: SOF/VEL; Drug: RBV

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Créteil, France, 94010
    • Hôpital Henri Mondor
  • Villejuif, France, 94800
    • Hôpital Paul Brousse
• United States
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Medical Group
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital; Clinical Research Unit
  • Maryland
    • Catonsville, Maryland, United States, 21228
      • Digestive Disease Associates, PA
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Southern Therapy and Advanced Research LLC
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Texas
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at Texas Liver Institute
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Liver Disease and Transplant Center
  • Virginia
    • Richmond, Virginia, United States, 23226
      • Bon Secours St. Mary's Hospital of Richmond, Inc. d/b/a Bon Secours Liver Institute of Virginia
  • Washington
    • Seattle, Washington, United States, 98105
      • University of Washington/ Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• A body mass index (BMI) of ≥ 18 kg/m^2
• Chronic HCV infection (≥ 6 months) as documented by either prior medical history or liver biopsy
• Quantifiable HCV RNA at screening

• Individuals may be non-transplanted or with recurrent HCV post-liver transplant.

  • If listed for liver transplant, then the projected date of transplant must be ≥12 weeks after Day1 of treatment
  • If post-liver transplant, then Day1 must be ≥ 6 months from date of transplant
• CPT score of 10 to 12, inclusive, as determined at screening
• Liver imaging within 6 months of Day 1 to exclude hepatocellular carcinoma (HCC)
• If treatment-experienced, the most recent HCV treatment must have been completed at least 8 weeks prior to Screening
• Females of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 prior to randomization
• Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Females must agree to refrain from egg donation and in vitro fertilization during treatment until at least 30 days after the last dose of SOF/VEL or 6 months after the last dose of RBV, whichever occurs last
• Lactating females must agree to discontinue nursing before the study drugs are administered
• Males must agree to refrain from sperm donation from the date of screening until at least 7 months after the last dose of RBV or 30 days after the last dose of SOF/VEL, whichever occurs last
• Adults must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments

Key Exclusion Criteria:

• Current or prior history of any of the following:

  • Clinically significant medical or psychiatric illness or individual is currently under evaluation for a potentially clinically significant illness
  • Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug
  • Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy
  • Significant pulmonary disease, significant cardiac disease or porphyria
  • Malignancy within the 5 years prior to screening, with the exception of specific cancers that have been cured by surgical resection (basal cell skin cancer, etc.). Adults under evaluation for possible malignancy are not eligible
  • Significant drug allergy (such as anaphylaxis or hepatotoxicity)
• Any history of organ transplant other than liver or kidney
• Chronic liver disease of a non-HCV etiology
• Inability to exclude HCC by imaging within 6 months of Day 1
• Alpha-fetoprotein (AFP) > 50 unless negative imaging for hepatic masses within the last 6 months or during screening
• Active spontaneous bacterial peritonitis at screening
• Infection requiring systemic antibiotics at the time of screening
• Evidence of fibrosing cholestatic hepatitis at screening
• Life threatening serious adverse event (SAE) during screening
• Active variceal bleeding within 6 months of screening
• Prior placement of a portosystemic shunt (such as TIPS)
• ECG with clinically significant abnormalities
• Laboratory parameters with clinically significant abnormalities
• Hepatitis B surface antigen positive at screening
• Infection with human immunodeficiency virus (HIV)
• Clinically-relevant alcohol or drug abuse within 12 months of screening. A positive drug screen will exclude individuals unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the Investigator
• Prior exposure to any HCV Non-structural Protein 5A (NS5A) inhibitor
• Current use of corticosteroids at any dose >10 mg of prednisone/day (or equivalent dose of corticosteroid)
• Use of any prohibited concomitant medications
• Use of granulocyte macrophage colony-stimulating factor (GM-CSF), epoetin alfa or other hematopoietic stimulating agents within 2 weeks of screening
• Male with pregnant female partner
• History of clinically significant hemoglobinopathy (eg, sickle cell disease, thalassemia)
• Contraindications to RBV therapy
• Known hypersensitivity to VEL, RBV, SOF, the metabolites, or formulation excipients
• Participation in a clinical study with an investigational drug or biologic within 3 months prior to Day 1

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SOF/VEL+ RBV; SOF/VEL FDC plus RBV for 12 weeks	Drug: SOF/VEL; 400/100 mg FDC tablet administered orally once daily; Other Names: Epclusa®; GS-7977/GS-5816; Drug: RBV; Tablets administered orally at 600 mg, if well tolerated then up to a maximum total daily dose of 1000 to 1200 mg (based on weight) divided twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.	Posttreatment Week 12
Percentage of Participants Who Permanently Discontinued Study Drug (SOF/VEL or RBV) Due to an Adverse Event		First dose date up to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4)	SVR4 was defined as HCV RNA < LLOQ 4 weeks after stopping study treatment.	Posttreatment Week 4
Percentage of Participants With a Decrease, No Change, or Increase in Model for End Stage Liver Disease (MELD) Score	MELD score is a chronic liver disease severity scoring system. Scores can range from 6 to 40, with higher scores indicating greater disease severity. "No change" was assigned for differences (posttreatment visits minus baseline score) of -1, 0 or 1; "Decrease" was assigned for differences that were less than or equal to -2; and "Increase" was assigned for values that were greater than or equal to 2.	Baseline to Posttreatment Week 24
Percentage of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24)	SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.	Posttreatment Week 24
Percentage of Participants With HCV RNA < LLOQ While on Study Treatment		Weeks 2, 4, 8, and 12
Percentage of Participants With No Change, Improved, and Worsened Child-Pugh-Turcotte (CPT) Class	CPT is a chronic liver disease classification system. Classes include CPT Class A, CPT Class B, and CPT Class C, in order of greater disease severity. Participants with improved CPT class was defined as having Class C at Baseline and Class B or A at Posttreatment Week 24 or Class B at Baseline and Class A at Posttreatment Week 24. Participants with worsened CPT class was defined as having Class A at Baseline and Class B or C at Posttreatment Week 24 or Class B at Baseline and Class C at Posttreatment Week 24. Participants with no change CPT class was defined as having CPT Class same between Baseline and Posttreatment Week 24.	Baseline to Posttreatment Week 24
Absolute HCV RNA Level Through Week 12		Baseline; Weeks 2, 4, 8, and 12
Change From Baseline in HCV RNA		Baseline; Weeks 2, 4, 8, and 12
Number of Participants With Virologic Failure	Virologic failure was defined as: On-treatment virologic failure:Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), orRebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), orNon-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment); Virologic relapse:Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit	Baseline up to Posttreatment Week 24

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Flamm S, Lawitz E, Borg B, Charlton M, Landis C, Reddy R, et al. High Efficacy and Improvement in CPT Class With Sofosbuvir/Velpatasvir Plus Ribavirin for 12 Weeks in Patients With CPT C Decompensated Cirrhosis [Poster THU-138]. EASL: The International Liver Congress; 2019 10-14 April; Vienna, Austria.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 23, 2017
• Primary Completion (ACTUAL): September 25, 2018
• Study Completion (ACTUAL): December 12, 2018

Study Registration Dates

• First Submitted: December 13, 2016
• First Submitted That Met QC Criteria: December 13, 2016
• First Posted (ESTIMATE): December 15, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 2, 2020
• Last Update Submitted That Met QC Criteria: February 18, 2020
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Infections; Communicable Diseases; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Sofosbuvir-velpatasvir drug combination; Velpatasvir
• Other Study ID Numbers: GS-US-342-4022; 2016-003066-10 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No