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

Hepatitis C Virus Infection Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02201901
• Other study ID #: GS-US-342-1137
• Status: Completed
• Phase: Phase 3
• Start date: July 2014
• Est. completion date: November 2015

Study information

• Verified date: October 2016
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 268
• Est. completion date: November 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Fibrosis
• Hepatitis
• Hepatitis C
• Hepatitis C Virus Infection
• Infection
• Liver Cirrhosis
• Virus Diseases

Intervention

Drug:
• SOF/VEL
400/100 mg tablets administered orally once daily
• 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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (3)

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.

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.

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 Inves — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Posttreatment Week 12
Primary	Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event		Up to 24 weeks plus 30 days
Secondary	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.	Posttreatment Weeks 4 and 24
Secondary	Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24		Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
Secondary	Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24		Baseline; Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24
Secondary	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	Up to Posttreatment Week 24
Secondary	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.	Baseline to Posttreatment Week 24
Secondary	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.	Baseline to Posttreatment Week 24