Clinical trial NCT02745535: Safety, Tolerability and Efficacy of Sofosbuvir, Velpatasvir, and Voxilaprevir in Subjects With Previous DAA Experience
Official title: Safety, Tolerability and Efficacy of Sofosbuvir, Velpatasvir, and Voxilaprevir in Subjects With Previous DAA Experience
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis C
Keywords: Hepatitis C relapse
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Unity Health Care, Inc.
name: Gilead Sciences
First posted: 2016-04-20
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Grade 3 and 4 Adverse Events
timeFrame: up to 16 weeks
measure: Number of Participants Who Achieve Sustained Virologic Response (SVR) 12 Weeks After Completion of Therapy (SVR12)
timeFrame: Post-treatment week 12
Secondary outcomes:
measure: Number of Participants Who Achieve End of Treatment Virologic Response (ETR) at Completion of Therapy.
timeFrame: Week 12
measure: Number of Participants Who Achieve Sustained Virologic Response (SVR) 4 Weeks After Completion of Therapy.
timeFrame: Post-treatment week 4
measure: Number of Participants Who Achieve Sustained Virologic Response (SVR) 24 Weeks After Completion of Therapy.
timeFrame: Post-treatment week 24
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Institute of Human Virology
state: Maryland
Study officials:
affiliation: University of Maryland Institute of Virology
name: Eleanor Wilson, MD
role: PRINCIPAL_INVESTIGATOR
References: