Clinical trial NCT02994056: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C Virus Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-12-15
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
timeFrame: Posttreatment Week 12
measure: Percentage of Participants Who Permanently Discontinued Study Drug (SOF/VEL or RBV) Due to an Adverse Event
timeFrame: First dose date up to Week 12
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4)
timeFrame: Posttreatment Week 4
measure: Percentage of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24)
timeFrame: Posttreatment Week 24
measure: Percentage of Participants With HCV RNA < LLOQ While on Study Treatment
timeFrame: Weeks 2, 4, 8, and 12
measure: Percentage of Participants With No Change, Improved, and Worsened Child-Pugh-Turcotte (CPT) Class
timeFrame: Baseline to Posttreatment Week 24
measure: Percentage of Participants With a Decrease, No Change, or Increase in Model for End Stage Liver Disease (MELD) Score
timeFrame: Baseline to Posttreatment Week 24
measure: Absolute HCV RNA Level Through Week 12
timeFrame: Baseline; Weeks 2, 4, 8, and 12
measure: Change From Baseline in HCV RNA
timeFrame: Baseline; Weeks 2, 4, 8, and 12
measure: Number of Participants With Virologic Failure
timeFrame: Baseline up to Posttreatment Week 24
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Tampa General Medical Group
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital; Clinical Research Unit
state: Illinois
city: Catonsville
country: United States
facility: Digestive Disease Associates, PA
state: Maryland
city: Jackson
country: United States
facility: Southern Therapy and Advanced Research LLC
state: Mississippi
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: San Antonio
country: United States
facility: American Research Corporation at Texas Liver Institute
state: Texas
city: Murray
country: United States
facility: Intermountain Liver Disease and Transplant Center
state: Utah
city: Richmond
country: United States
facility: Bon Secours St. Mary's Hospital of Richmond, Inc. d/b/a Bon Secours Liver Institute of Virginia
state: Virginia
city: Seattle
country: United States
facility: University of Washington/ Harborview Medical Center
state: Washington
city: Créteil
country: France
facility: Hopital Henri Mondor
city: Villejuif
country: France
facility: Hopital Paul Brousse
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.