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Sofosbuvir/Velpatasvir Fixed-Dose Combination in Adults With Chronic HCV Infection and Child-Pugh Class B Cirrhosis (ASTRAL-4)

Primary Purpose

Hepatitis C Virus Infection

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
SOF/VEL
RBV
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C Virus Infection focused on measuring Sofosbuvir, Velpatasvir, SOF/VEL, GS-5816, Hepatitis C, HCV, Cirrhosis, CPT-B

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

SOF/VEL 12 weeks

SOF/VEL+RBV 12 weeks

SOF/VEL 24 weeks

Arm Description

Participants will receive SOF/VEL FDC for 12 weeks.

Participants will receive SOF/VEL FDC plus RBV for 12 weeks.

Participants will receive SOF/VEL FDC for 24 weeks.

Outcomes

Primary Outcome Measures

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) 12 weeks following the last dose of study drug.
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event

Secondary Outcome Measures

Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
Percentage of Participants With Virologic Failure
Virologic failure was defined as On-treatment virologic failure HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie nonresponse) Relapse HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement
Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score
Model for End-Stage Liver Disease (MELD) scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40; higher scores/increased scores indicate greater severity of disease.
Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score
CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15; higher scores/increased scores indicate greater severity of disease.

Full Information

First Posted
July 24, 2014
Last Updated
October 19, 2018
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02201901
Brief Title
Sofosbuvir/Velpatasvir Fixed-Dose Combination in Adults With Chronic HCV Infection and Child-Pugh Class B Cirrhosis
Acronym
ASTRAL-4
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

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
July 2014 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Virus Infection
Keywords
Sofosbuvir, Velpatasvir, SOF/VEL, GS-5816, Hepatitis C, HCV, Cirrhosis, CPT-B

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
268 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SOF/VEL 12 weeks
Arm Type
Experimental
Arm Description
Participants will receive SOF/VEL FDC for 12 weeks.
Arm Title
SOF/VEL+RBV 12 weeks
Arm Type
Experimental
Arm Description
Participants will receive SOF/VEL FDC plus RBV for 12 weeks.
Arm Title
SOF/VEL 24 weeks
Arm Type
Experimental
Arm Description
Participants will receive SOF/VEL FDC for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
SOF/VEL
Other Intervention Name(s)
GS-7977/GS-5816, Epclusa®
Intervention Description
400/100 mg tablets administered orally once daily
Intervention Type
Drug
Intervention Name(s)
RBV
Intervention Description
Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Description
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
Time Frame
Posttreatment Week 12
Title
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time Frame
Up to 24 weeks plus 30 days
Secondary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
Description
SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
Time Frame
Posttreatment Weeks 4 and 24
Title
Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
Time Frame
Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
Title
Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
Time Frame
Baseline; Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
Title
Percentage of Participants With Virologic Failure
Description
Virologic failure was defined as On-treatment virologic failure HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie nonresponse) Relapse HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement
Time Frame
Up to Posttreatment Week 24
Title
Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score
Description
Model for End-Stage Liver Disease (MELD) scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40; higher scores/increased scores indicate greater severity of disease.
Time Frame
Baseline to Posttreatment Week 24
Title
Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score
Description
CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15; higher scores/increased scores indicate greater severity of disease.
Time Frame
Baseline to Posttreatment Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anu M Osinusi, MD, MPH
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Phoenix
State/Province
Arizona
Country
United States
City
La Jolla
State/Province
California
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
City
Los Angeles
State/Province
California
Country
United States
City
Pasadena
State/Province
California
Country
United States
City
San Francisco
State/Province
California
Country
United States
City
Aurora
State/Province
Colorado
Country
United States
City
Washington
State/Province
District of Columbia
Country
United States
City
Gainesville
State/Province
Florida
Country
United States
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32256
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
Tampa
State/Province
Florida
Country
United States
City
Marietta
State/Province
Georgia
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
City
Kansas City
State/Province
Kansas
Country
United States
City
Monroe
State/Province
Louisiana
ZIP/Postal Code
71280
Country
United States
City
New Orleans
State/Province
Louisiana
Country
United States
City
Baltimore
State/Province
Maryland
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Ann Arbor
State/Province
Michigan
Country
United States
City
Detroit
State/Province
Michigan
Country
United States
City
Rochester
State/Province
Minnesota
Country
United States
City
Jackson
State/Province
Mississippi
Country
United States
City
Saint Louis
State/Province
Missouri
Country
United States
City
Santa Fe
State/Province
New Mexico
ZIP/Postal Code
87505
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
City
Chapel Hill
State/Province
North Carolina
Country
United States
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
City
Durham
State/Province
North Carolina
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
City
Cleveland
State/Province
Ohio
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37211
Country
United States
City
Arlington
State/Province
Texas
ZIP/Postal Code
76012
Country
United States
City
Dallas
State/Province
Texas
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
Murray
State/Province
Utah
Country
United States
City
Fairfax
State/Province
Virginia
Country
United States
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
City
Richmond
State/Province
Virginia
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
San Juan
ZIP/Postal Code
00927
Country
Puerto Rico

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
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 URL
http://www.gilead.com/research/disclosure-and-transparency
Citations:
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.
Results Reference
background
PubMed Identifier
26569658
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.
Results Reference
result
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.
Results Reference
result
PubMed Identifier
28404069
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.
Results Reference
derived
PubMed Identifier
27847279
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.
Results Reference
derived

Learn more about this trial

Sofosbuvir/Velpatasvir Fixed-Dose Combination in Adults With Chronic HCV Infection and Child-Pugh Class B Cirrhosis

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