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

University of Maryland Baltimore (UMB)

Status and phase

Completed

Phase 2

Conditions

Chronic Hepatitis C

Treatments

Drug: Sofosbuvir/Velpatasvir/Voxilaprevir

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02745535

HP-00067213

Details and patient eligibility

About

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.

Full 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

Enrollment

77 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.