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

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ClinicalTrials.gov Identifier: NCT02745535
Recruitment Status : Completed
First Posted : April 20, 2016
Results First Posted : March 27, 2019
Last Update Posted : March 27, 2019
Sponsor:
Collaborators:
Unity Health Care, Inc.
Gilead Sciences
Information provided by (Responsible Party):
Eleanor Wilson, University of Maryland

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.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis C Drug: Sofosbuvir/Velpatasvir/Voxilaprevir Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety, Tolerability and Efficacy of Sofosbuvir, Velpatasvir, and Voxilaprevir in Subjects With Previous DAA Experience
Actual Study Start Date : May 2016
Actual Primary Completion Date : October 24, 2018
Actual Study Completion Date : October 24, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Sofosbuvir

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:
  • SOF/VEL/VOX
  • GS-7977/GS-5816/GS-9857




Primary Outcome Measures :
  1. Number of Participants With Grade 3 and 4 Adverse Events [ Time Frame: up to 16 weeks ]
    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

  2. Number of Participants Who Achieve Sustained Virologic Response (SVR) 12 Weeks After Completion of Therapy (SVR12) [ Time Frame: Post-treatment week 12 ]
    Intention to treat (ITT) analysis. Sustained Virologic Response as measure by an undetectable HCV RNA level 12 weeks after completion of therapy.


Secondary Outcome Measures :
  1. Number of Participants Who Achieve End of Treatment Virologic Response (ETR) at Completion of Therapy. [ Time Frame: Week 12 ]
    Per protocol analysis. End of Treatment Virologic Response as measure by an undetectable HCV RNA level completion of therapy.

  2. Number of Participants Who Achieve Sustained Virologic Response (SVR) 4 Weeks After Completion of Therapy. [ Time Frame: Post-treatment week 4 ]
    Per protocol analysis. Sustained Virologic Response as measure by an undetectable HCV RNA level 4 weeks after completion of therapy.

  3. Number of Participants Who Achieve Sustained Virologic Response (SVR) 24 Weeks After Completion of Therapy. [ Time Frame: Post-treatment week 24 ]
    Per protocol analysis. Sustained Virologic Response as measure by an undetectable HCV RNA level 24 weeks after completion of therapy.



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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:

  • 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.

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): NCT02745535


Locations
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United States, Maryland
Institute of Human Virology
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
University of Maryland
Unity Health Care, Inc.
Gilead Sciences
Investigators
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Principal Investigator: Eleanor Wilson, MD University of Maryland Institute of Virology
  Study Documents (Full-Text)

Documents provided by Eleanor Wilson, University of Maryland:

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Responsible Party: Eleanor Wilson, Assistant Professor, University of Maryland
ClinicalTrials.gov Identifier: NCT02745535     History of Changes
Other Study ID Numbers: HP-00067213
First Posted: April 20, 2016    Key Record Dates
Results First Posted: March 27, 2019
Last Update Posted: March 27, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No individual participant data will be made available.

Keywords provided by Eleanor Wilson, University of Maryland:
Hepatitis C relapse

Additional relevant MeSH terms:
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Hepatitis
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Sofosbuvir
Velpatasvir
Sofosbuvir-velpatasvir drug combination
Antiviral Agents
Anti-Infective Agents