Clinical trial NCT02201901: Sofosbuvir/Velpatasvir Fixed-Dose Combination in Adults With Chronic HCV Infection and Child-Pugh Class B Cirrhosis
Official title: A Phase 3, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5816 Fixed-Dose Combination in Subjects With Chronic HCV Infection and Child-Pugh Class B Cirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C Virus Infection
Keywords: Sofosbuvir
Velpatasvir
SOF/VEL
GS-5816
Hepatitis C
HCV
Cirrhosis
CPT-B
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-07-28
Enrollment: 268
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of sofosbuvir (SOF)/velpatasvir (VEL) fixed dose combination (FDC) with and without ribavirin (RBV) for 12 weeks and SOF/VEL FDC for 24 weeks in adults with chronic hepatitis C virus (HCV) infection and Child-Pugh-Turcotte (CPT) class B cirrhosis.


Eligibility criteria: Inclusion Criteria:

* Willing and able to provide written informed consent
* HCV RNA \> 10\^4 IU/mL at screening
* Chronic HCV infection (≥ 6 months)
* Confirmed CPT class B (7-9) at screening

Exclusion Criteria:

* Current or prior history of solid organ transplantation, significant pulmonary disease, significant cardiac disease, or porphyria
* Inability to exclude hepatocellular carcinoma (HCC) by imaging within 6 months of baseline/Day 1
* Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
* Screening ECG with clinically significant abnormalities
* Prior exposure to SOF or any other nucleotide analogue HCV nonstructural protein 5B (NS5B) inhibitor or any HCV NS5A inhibitor
* Laboratory results outside of acceptable ranges at screening

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 Any Study Drug Due to an Adverse Event
timeFrame: Up to 24 weeks plus 30 days
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
timeFrame: Posttreatment Weeks 4 and 24
measure: Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
timeFrame: Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
measure: Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
timeFrame: Baseline; Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
measure: Percentage of Participants With Virologic Failure
timeFrame: Up to Posttreatment Week 24
measure: Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score
timeFrame: Baseline to Posttreatment Week 24
measure: Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score
timeFrame: Baseline to Posttreatment Week 24
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Pasadena
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Gainesville
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Marietta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Kansas City
country: United States
state: Kansas
city: Monroe
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Rochester
country: United States
state: Minnesota
city: Jackson
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: Santa Fe
country: United States
state: New Mexico
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Providence
country: United States
state: Rhode Island
city: Germantown
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Murray
country: United States
state: Utah
city: Fairfax
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: San Juan
country: Puerto Rico
Study officials:
affiliation: Gilead Sciences
name: Anu M Osinusi, MD, MPH
role: STUDY_DIRECTOR
References:
citation: Charlton MR, O'Leary JG, Bzowej NH, Muir AJ, Korenblat KM, Fenkel JM, et al. Sofosbuvir/Velapatasvir Fixed Dose Combination for the Treatment of HCV in Patients with Decompensated Liver Disease: The Phase 3 ASTRAL-4 Study. Hepatology 2015; 62 (6): 1387A-1388A.
citation: Curry MP, O'Leary JG, Bzowej N, Muir AJ, Korenblat KM, Fenkel JM, Reddy KR, Lawitz E, Flamm SL, Schiano T, Teperman L, Fontana R, Schiff E, Fried M, Doehle B, An D, McNally J, Osinusi A, Brainard DM, McHutchison JG, Brown RS Jr, Charlton M; ASTRAL-4 Investigators. Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis. N Engl J Med. 2015 Dec 31;373(27):2618-28. doi: 10.1056/NEJMoa1512614. Epub 2015 Nov 16.
citation: Asselah T, Charlton M, Feld J, Foster GR, McNally J, Brainard DM, et al. The ASTRAL Studies: Evaluation of SOF/GS-5816 Single-Tablet Regimen for the Treatment of Genotype 1-6 HCV Infection [Poster P1332]. J Hepatol 2015; 62:S855-S6.
citation: Younossi ZM, Stepanova M, Charlton M, Curry MP, O'Leary JG, Brown RS, Hunt S. Patient-reported outcomes with sofosbuvir and velpatasvir with or without ribavirin for hepatitis C virus-related decompensated cirrhosis: an exploratory analysis from the randomised, open-label ASTRAL-4 phase 3 trial. Lancet Gastroenterol Hepatol. 2016 Oct;1(2):122-132. doi: 10.1016/S2468-1253(16)30009-7. Epub 2016 Aug 3.
citation: Younossi ZM, Stepanova M, Feld J, Zeuzem S, Sulkowski M, Foster GR, Mangia A, Charlton M, O'Leary JG, Curry MP, Nader F, Henry L, Hunt S. Sofosbuvir and Velpatasvir Combination Improves Patient-reported Outcomes for Patients With HCV Infection, Without or With Compensated or Decompensated Cirrhosis. Clin Gastroenterol Hepatol. 2017 Mar;15(3):421-430.e6. doi: 10.1016/j.cgh.2016.10.037. Epub 2016 Nov 12.