Chronic Hepatitis CPhase 2RESOLVENCT02745535
Safety, Tolerability and Efficacy of Sofosbuvir, Velpatasvir, and Voxilaprevir in Subjects With Previous DAA Experience
A Phase 2 study testing Sofosbuvir/Velpatasvir/Voxilaprevir in people with Chronic Hepatitis C, run by University of Maryland, Baltimore at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- Sofosbuvir/Velpatasvir/Voxilaprevir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 1 siteUnited States
- Study dates
- May 2016to 24 Oct 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- HIV coinfected participants must have HIV status of one of the following:
- HIV untreated for >8 weeks prior to screening, CD4 >500, no intention of initiating ARV therapy for the duration of the trial.
- HIV suppressed on a stable, protocol-approved ARV regimen for >4 weeks prior to screening.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Institute of Human Virology
Baltimore, Maryland, 21201
About this study
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.
Read the 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
- Conditions
- Chronic Hepatitis C
- Being tested
- Sofosbuvir/Velpatasvir/Voxilaprevir
- Keywords
- Hepatitis C relapse
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sofosbuvir/Velpatasvir/VoxilaprevirDrug
Also called SOF/VEL/VOX, GS-7977/GS-5816/GS-9857
| Study group | Role | What they receive |
|---|---|---|
| SOF/VEL/VOX | Experimental | Fixed dose combination of SOF/VEL/VOX (Sofosbuvir 400mg/Velpatasvir 100mg/ Voxilaprevir 100mg) dosed once daily for 12 weeks. Receives: Drug: Sofosbuvir/Velpatasvir/Voxilaprevir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: Post-treatment week 12
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: Post-treatment week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2016 (estimated)
- Study startMay 2016
- Primary completion24 Oct 2018
- Study completion24 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- Unity Health Care, Inc., Gilead Sciences
- Responsible party
- Principal investigator, Eleanor Wilson, University of Maryland, Baltimore
- Investigators
- Eleanor Wilson, MD, Principal investigator, University of Maryland Institute of Virology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02745535
- Sponsor's protocol ID
- HP-00067213
- Acronym
- RESOLVE
- Status last verified
- Mar 2022
- First submitted
- 11 Apr 2016
- Last updated
- 10 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: No individual participant data will be made available.
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Tolerability and Efficacy of Sofosbuvir, Velpatasvir, and Voxilaprevir in Subjects With Previous DAA Experience
- ClinicalTrials.gov ID
- NCT02745535
- Acronym / sponsor ID
- RESOLVE / HP-00067213
- Conditions
- Chronic Hepatitis C
- Keywords
- Hepatitis C relapse
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- Unity Health Care, Inc., Gilead Sciences
- Study start
- May 2016 (actual)
- Primary completion
- 24 Oct 2018 (actual)
- Study completion
- 24 Oct 2018 (actual)
- First posted
- 20 Apr 2016 (estimated)
- Results
- Posted 27 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SOF/VEL/VOX | Experimental | Drug: Sofosbuvir/Velpatasvir/VoxilaprevirFixed dose combination of SOF/VEL/VOX (Sofosbuvir 400mg/Velpatasvir 100mg/ Voxilaprevir 100mg) dosed once daily for 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sofosbuvir/Velpatasvir/VoxilaprevirAlso: SOF/VEL/VOX, GS-7977/GS-5816/GS-9857 | Drug | SOF/VEL/VOX |
Primary outcome
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
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.
3 secondary outcomes
Number of Participants Who Achieve End of Treatment Virologic Response (ETR) at Completion of Therapy.
Time frame: Week 12
Number of Participants Who Achieve Sustained Virologic Response (SVR) 4 Weeks After Completion of Therapy.
Time frame: Post-treatment week 4
Number of Participants Who Achieve Sustained Virologic Response (SVR) 24 Weeks After Completion of Therapy.
Time frame: Post-treatment week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. No individual participant data will be made available.
Related trials for Chronic Hepatitis C
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eleanor Wilson, MD principal investigator
University of Maryland Institute of Virology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sofosbuvir/Velpatasvir/Voxilaprevir in people with Chronic Hepatitis C, run by University of Maryland, Baltimore at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Grade 3 and 4 Adverse Events (time frame: up to 16 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2022.