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

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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

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.

Condition or disease Intervention/treatment Phase
Hepatitis C Virus Infection Drug: SOF/VEL Drug: RBV Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 268 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : July 2014
Actual Primary Completion Date : August 2015
Actual Study Completion Date : November 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Sofosbuvir

Arm Intervention/treatment
Experimental: SOF/VEL 12 weeks
Participants will receive SOF/VEL FDC for 12 weeks.
Drug: SOF/VEL
400/100 mg tablets administered orally once daily
Other Names:
  • GS-7977/GS-5816
  • Epclusa®

Experimental: SOF/VEL+RBV 12 weeks
Participants will receive SOF/VEL FDC plus RBV for 12 weeks.
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)

Experimental: SOF/VEL 24 weeks
Participants will receive SOF/VEL FDC for 24 weeks.
Drug: SOF/VEL
400/100 mg tablets administered orally once daily
Other Names:
  • GS-7977/GS-5816
  • Epclusa®




Primary Outcome Measures :
  1. 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.

  2. 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 Measures :
  1. 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.

  2. 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 ]
  3. 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 ]
  4. 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

  5. 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.

  6. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02201901


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Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Anu M Osinusi, MD, MPH Gilead Sciences

Publications of Results:
Other Publications:
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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02201901     History of Changes
Other Study ID Numbers: GS-US-342-1137
First Posted: July 28, 2014    Key Record Dates
Results First Posted: December 14, 2016
Last Update Posted: November 15, 2018
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
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
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

Keywords provided by Gilead Sciences:
Sofosbuvir
Velpatasvir
SOF/VEL
GS-5816
Hepatitis C
HCV
Cirrhosis
CPT-B

Additional relevant MeSH terms:
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Infection
Communicable Diseases
Hepatitis
Hepatitis C
Fibrosis
Liver Cirrhosis
Virus Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Flaviviridae Infections
RNA Virus Infections
Pathologic Processes
Sofosbuvir
Velpatasvir
Antiviral Agents
Anti-Infective Agents