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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02201901
Recruitment Status : Completed
First Posted : July 28, 2014
Results First Posted : December 14, 2016
Last Update Posted : November 15, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE July 24, 2014
First Posted Date  ICMJE July 28, 2014
Results First Submitted Date  ICMJE August 24, 2016
Results First Posted Date  ICMJE December 14, 2016
Last Update Posted Date November 15, 2018
Study Start Date  ICMJE July 2014
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 24, 2016)
  • Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
    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 [ Time Frame: Up to 24 weeks plus 30 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 24, 2014)
  • Proportion of participants with sustained virologic response 12 weeks after discontinuation of therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
    SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
  • Incidence of adverse events leading to permanent discontinuation of study drug(s) [ Time Frame: Up to 24 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2016)
  • Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ]
    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 [ Time Frame: 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 [ Time Frame: Baseline; Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 ]
  • Percentage of Participants With Virologic Failure [ Time Frame: Up to Posttreatment Week 24 ]
    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 [ Time Frame: Baseline to Posttreatment Week 24 ]
    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 [ Time Frame: Baseline to Posttreatment Week 24 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2014)
  • Proportion of participants with sustained virologic response 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ]
    SVR4 and SVR24 are defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
  • Proportion of participants with HCV RNA < LLOQ on treatment [ Time Frame: Up to 8 weeks ]
  • Model for end-stage liver disease (MELD) and CPT score changes from baseline [ Time Frame: Up to Posttreatment Week 24 ]
  • HCV RNA change from baseline [ Time Frame: Up to 8 weeks ]
  • Proportion of participants with virologic failure [ Time Frame: Up to Posttreatment Week 24 ]
    Virologic failure is 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sofosbuvir/Velpatasvir Fixed-Dose Combination in Adults With Chronic HCV Infection and Child-Pugh Class B Cirrhosis
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatitis C Virus Infection
Intervention  ICMJE
  • Drug: SOF/VEL
    400/100 mg tablets administered orally once daily
    Other Names:
    • GS-7977/GS-5816
    • Epclusa®
  • Drug: RBV
    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)
Study Arms  ICMJE
  • Experimental: SOF/VEL 12 weeks
    Participants will receive SOF/VEL FDC for 12 weeks.
    Intervention: Drug: SOF/VEL
  • Experimental: SOF/VEL+RBV 12 weeks
    Participants will receive SOF/VEL FDC plus RBV for 12 weeks.
    Interventions:
    • Drug: SOF/VEL
    • Drug: RBV
  • Experimental: SOF/VEL 24 weeks
    Participants will receive SOF/VEL FDC for 24 weeks.
    Intervention: Drug: SOF/VEL
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 2, 2015)
268
Original Estimated Enrollment  ICMJE
 (submitted: July 24, 2014)
225
Actual Study Completion Date  ICMJE November 2015
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02201901
Other Study ID Numbers  ICMJE GS-US-342-1137
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: http://www.gilead.com/research/disclosure-and-transparency
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Anu M Osinusi, MD, MPH Gilead Sciences
PRS Account Gilead Sciences
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP