Safety, Tolerability and Efficacy of Sofosbuvir, Velpatasvir, and Voxilaprevir in Subjects With Previous DAA Experience (RESOLVE)

This study will evaluate the safety, tolerability, and efficacy of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in adults with chronic hepatitis C infection who have failed to eradicate hepatitis C despite previous combination directly acting antiviral therapy.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: Sofosbuvir/Velpatasvir/Voxilaprevir

Detailed Description

The treatment of chronic Hepatitis C with combination directly acting antiviral agents (DAAs) represents a dramatic improvement over previous therapies in safety, tolerability and efficacy, but these therapies are not universally effective. Some patients fail to achieve sustained virologic response (SVR) following therapy with combination DAAs, yet the ideal retreatment strategy for these patients has not yet been determined. As DAA medications become more widely available outside clinical trial settings, it is important to evaluate retreatment strategies in patients who fail combination DAA therapy, regardless of whether they had virologic failure, post-treatment relapse, or discontinued treatment prematurely.

The RESOLVE study will evaluate the safety, tolerability, and efficacy of treatment with a fixed dose combination of sofosbuvir (an approved NS5B inhibitor), velpatasvir (formerly GS-5816, a second generation NS5A inhibitor) and voxilaprevir (formerly GS-9857, an approved NS3/4A protease inhibitor) in HCV infected patients with early and advanced liver disease, including those with HIV or hepatitis B, who have failed previous combination DAA therapy. Patients with early stage and compensated cirrhosis will receive 12 weeks of therapy, and be followed for adverse events and SVR following completion of therapy.

RESOLVE will aid our understanding of the determinants of response to re-treatment with combination DAA therapy

• With and without cirrhosis
• In patients with HCV GT1 subtypes a and b
• In patients who previously failed DAA therapy
• With and without HIV or hepatitis B

RESOLVE will also examine factors associated with treatment response, including

• the viral and pharmacokinetics of patients receiving the combination of SOF/VEL/VOX, in patients with and without cirrhosis
• differential interferon sensitive gene responses
• host genetic and proteomic factors
• evolution of HCV quasispecies and resistance associated variants at baseline and in response to therapy
• changes in host HCV-specific immunity in patients with and without advanced liver disease

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Institute of Human Virology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Available for clinical follow-up through Week 44 after enrollment.
• Recurrent HCV GT-1
• Exposure to combination DAA therapy
• Able and willing to complete the informed consent process.
• Use of protocol specified methods of contraception
• Hepatitis B coinfected participants must have evidence of chronic infection and controlled on treatment

• HIV coinfected participants must have HIV status of one of the following:

  1. HIV untreated for >8 weeks prior to screening, CD4 >500, no intention of initiating ARV therapy for the duration of the trial.
  2. HIV suppressed on a stable, protocol-approved ARV regimen for >4 weeks prior to screening.

Exclusion Criteria:

• Combination DAA therapy was completed or discontinued less than 8 weeks prior to enrollment.
• Current or prior history of any clinically significant illness, organ transplantation, and/or concomitant medication that may interfere with the subject treatment, assessment of compliance with the protocol.
• Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, alfa-1 antitrypsin deficiency, cholangitis)
• Laboratory results outside acceptable ranges at screening.
• Female who is pregnant, breast-feeding or planning to become pregnant during study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SOF/VEL/VOX; Fixed dose combination of SOF/VEL/VOX (Sofosbuvir 400mg/Velpatasvir 100mg/ Voxilaprevir 100mg) dosed once daily for 12 weeks.	Drug: Sofosbuvir/Velpatasvir/Voxilaprevir; Other Names: GS-7977/GS-5816/GS-9857; SOF/VEL/VOX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Grade 3 and 4 Adverse Events	Number of participants with grade 3 and 4 adverse events during treatment with and/or within 30 of completion of SOF/VEL/VOX in HCV infected	up to 16 weeks
Number of Participants Who Achieve Sustained Virologic Response (SVR) 12 Weeks After Completion of Therapy (SVR12)	Intention to treat (ITT) analysis. Sustained Virologic Response as measure by an undetectable HCV RNA level 12 weeks after completion of therapy.	Post-treatment week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieve End of Treatment Virologic Response (ETR) at Completion of Therapy.	Per protocol analysis. End of Treatment Virologic Response as measure by an undetectable HCV RNA level completion of therapy.	Week 12
Number of Participants Who Achieve Sustained Virologic Response (SVR) 4 Weeks After Completion of Therapy.	Per protocol analysis. Sustained Virologic Response as measure by an undetectable HCV RNA level 4 weeks after completion of therapy.	Post-treatment week 4
Number of Participants Who Achieve Sustained Virologic Response (SVR) 24 Weeks After Completion of Therapy.	Per protocol analysis. Sustained Virologic Response as measure by an undetectable HCV RNA level 24 weeks after completion of therapy.	Post-treatment week 24

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: Gilead Sciences; Unity Health Care, Inc.
• Investigators: Principal Investigator: Eleanor Wilson, MD, University of Maryland Institute of Virology

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): October 24, 2018
• Study Completion (Actual): October 24, 2018

Study Registration Dates

• First Submitted: April 11, 2016
• First Submitted That Met QC Criteria: April 15, 2016
• First Posted (Estimate): April 20, 2016

Study Record Updates

• Last Update Posted (Actual): March 10, 2022
• Last Update Submitted That Met QC Criteria: March 8, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Hepatitis C relapse
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Hepatitis C; Hepatitis C, Chronic; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Sofosbuvir-velpatasvir drug combination; Velpatasvir
• Other Study ID Numbers: HP-00067213

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No individual participant data will be made available.