HCV CoinfectionPhase 4deLIVERNCT02938013
deLIVER: Direct Acting Antiviral Effects on the Liver
A Phase 4 study testing Sofosbuvir/Velpatasvir/Voxilaprevir [SOF/VEL/VOX] and Sofosbuvir/Velpatasvir (SOF/VEL) in people with HCV Coinfection and Liver Disease, run by Johns Hopkins University at 1 site in United States.
Trial summary
Open-label, partially-randomized plasma and liver sampling study to assess hepatitis C virus (HCV) kinetics during treatment with two (Sofosbuvir/Velpatasvir) or three (Sofosbuvir/Velpatasvir/Voxilaprevir) direct acting antivirals (DAAs) Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HCV Coinfection, Liver Disease, HIV
- What is being tested?
- Sofosbuvir/Velpatasvir/Voxilaprevir [SOF/VEL/VOX] and Sofosbuvir/Velpatasvir (SOF/VEL)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2017to 30 Sep 2020
- Phase
- Phase 4
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
- Breastfeeding.
- Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
- Acute or serious illness requiring systemic treatment and/or hospitalization within 42 days prior to study entry.
- Active hepatitis B infection (positive HBsAg) within 42 days prior to study entry.
- History of decompensated liver disease (including but not limited to encephalopathy, variceal bleeding, or ascites) prior to study entry.
Show all 25Show fewer
- Any cause of liver disease other than chronic HCV infection, including but not limited to the following:
- Hemochromatosis
- Alpha-1 antitrypsin deficiency
- Wilson's disease
- Autoimmune hepatitis
- Alcoholic liver disease
- Drug-related liver disease
- Uncontrolled or active depression or other psychiatric disorder within 24 weeks prior to study entry that in the opinion of the investigator might preclude adherence to study requirements.
- Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
- Serious illness including uncontrolled seizure disorders, active coronary artery disease within 24 weeks prior to study entry, or other chronic medical conditions that in the opinion of the investigator might preclude completion of the protocol.
- Presence of active or acute AIDS-defining opportunistic infections within 12 weeks prior to study entry.
- Active or history of malignancy within 2 years prior to study entry other than basal cell carcinoma of the skin and/or cutaneous Kaposi's sarcoma (KS) and/or cervical or anal dysplasia or carcinoma in situ.
- 13. Infection with any HCV genotype other than genotype 1a, or mixed genotype infection any time prior to study entry.
- 14. History of major organ transplantation with an existing functional graft any time prior to study entry.
- 15. History of acquired or hereditary bleeding disorder (e.g., hemophilia, warfarin use) or any other cause of or tendency toward excessive bleeding time prior to study entry.
- 16. Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug 17. Difficulty with blood collection and/or poor venous access for the purposes of phlebotomy 18. Planning to take any of the following medications or supplements from Day -7 to the end of treatment:
- Proton pump inhibitors (patients may switch to H2 blockers up to Day -7)
- Inducers of P-gp (including, but not limited to, dexamethasone, morphine, ritonavir, saquinavir, tipranavir)
- Moderate to potent inducers of CYP2B6, CYP2C8, or CYP3A4 (including, but not limited to, efavirenz, etavirine, modafinil, rifampin, St. John's Wort, carbamazepine, phenytoin) 19. History of taking any dose of amiodarone within 6 months (180 days) of Day 0
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins Hospital : The John G. Bartlett Specialty Practice
Baltimore, Maryland, 21287
About this study
Open-label, partially-randomized plasma and liver sampling study to assess hepatitis C virus (HCV) kinetics during treatment with two (Sofosbuvir/Velpatasvir) or three (Sofosbuvir/Velpatasvir/Voxilaprevir) direct acting antivirals (DAAs)
Read the detailed description
Primary Objective: The primary objective is to estimate the 1-week change in the proportion of HCV-infected hepatocytes in participants with HCV monoinfection and HIV/HCV coinfection on therapy with two or three DAAs with different mechanisms of action using single cell laser microdissection (scLCM).
Secondary Objectives:
Estimate the change over the first week in plasma HCV RNA in subjects with HCV monoinfected and HIV/HCV coinfected participants on therapy with two or three DAAs
Estimate the 1 week change in the amount of HCV RNA per infected hepatocyte using scLCM on liver biopsy specimens, obtained just prior to treatment initiation (pre-treatment), and after the first week of DAA therapy.
Estimate the change in the proportion of HCV-infected hepatocytes that express interferon-stimulated genes (ISGs) within the first week of DAA therapy using scLCM.
Measure the change in expression of ISGs in non-parenchymal intrahepatic immune cells (Kupffer cells, plasmacytoid dendritic cells) within the first week of DAA therapy using scLCM.
Exploratory Objectives:
Estimate the 1 week change in expression of ISGs from peripheral blood mononucleated cells (PBMCs) within the first week of DAA+ribavirin (RBV) therapy using scLCM.
Compare sequence(s) of HCV protease, nonstructural protein 5A (NS5A), and nonstructural protein 5B (NS5B) depending on the peripheral sequence) of intrahepatic HCV RNA in single cells and bulk tissue, before and during week 1 of DAA+RBV therapy.
Estimate the week 1 change in the sizes and numbers of HCV-infected clusters on DAA therapy to test whether clearance of HCV-infected hepatocytes occurs in spatially random patterns or within specific clusters.
- Conditions
- HCV Coinfection, Liver Disease, HIV
- Being tested
- Sofosbuvir/Velpatasvir/Voxilaprevir [SOF/VEL/VOX], Sofosbuvir/Velpatasvir (SOF/VEL)
- Medical subject headings
- Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sofosbuvir/Velpatasvir/Voxilaprevir [SOF/VEL/VOX]Drug
antiviral therapy for HCV
Sofosbuvir/Velpatasvir (SOF/VEL)Drug
antiviral therapy for HCV
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Monoinfected: Sofosbuvir/Velpatasvir/Voxilaprevir SOF/VEL/VOX days 0-7 Paired liver biopsy at days 0 and 7 (cohort 1) or days 0 and 4 (cohort 2). SOF/VEL days 8 (week 2) through 84 (week 12). Post-treatment follow up through week 12. Receives: Drug: Sofosbuvir/Velpatasvir/Voxilaprevir [SOF/VEL/VOX] |
| Group B | Active comparator | Monoinfected: Sofosbuvir/Velpatasvir (SOF/VEL) days 0 through 7 and Paired liver biopsy at days 0 and 7 (cohort 1) or days 0 and 4 (cohort 2). SOF/VEL on day 8 (week 2) through 84 (week 12) . Post-Treatment follow up through week 12. Receives: Drug: Sofosbuvir/Velpatasvir (SOF/VEL) |
| Group C | Active comparator | HIV/HCV Co-infection: Sofosbuvir/Velpatasvir (SOF/VEL) days 0 through 7 and Paired liver biopsy at days 0 and 7 (cohort 1) or days 0 and 4 (cohort 2). SOF/VEL on day 8 (week 2) through 84 (week 12) . Post-Treatment follow up through week 12. Receives: Drug: Sofosbuvir/Velpatasvir (SOF/VEL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy
Estimate the total number of HCV-infected Hepatocytes (virus burden) for each participant between pre-treatment liver biopsy and post treatment liver biopsy samples using HCV Quantitative real time PCR.
Comparison of total number of HCV-infected Hepatocytes (virus burden) were reported between HCV mono infection and co infection groups.
Measured: Pre-treatment, Day 7
Secondary outcomes (3)
Reduction Over the First Week in Plasma HCV RNA
During one week after treatment with direct-acting antivirals, the decline from the baseline plasma HCV RNA levels observed for each individual participant using HCV Quantitative real time PCR.
The level of HCV RNA decline compared to those treated with Sofosbuvir/Velpatasvir (SOF/VEL) vs Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) and between HCV mono infection and HIV/HCV co infection groups.
Measured: Pre-treatment, up to 1 week
Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM).
Total number of hepatocytes that express interferon-stimulated genes (ISGs) were estimated using Quantitative real time PCR for each participant on pre-treatment and post treatment liver biopsy samples.
Comparison of total number of hepatocytes that express interferon-stimulated genes (ISGs) were reported between HCV mono infection and co infection groups.
Measured: Pre-treatment, up to 1 week
Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy.
The HCV RNA levels (viral burden) from each infected hepatocytes were measured using Quantitative Real-Time Polymerase Chain Reaction (PCR) from each participants at pre-treatment and post-treatment.
The level of HCV RNA (viral burden) decline were reported from intracellular hepatocytes and compared to those treated with Sofosbuvir/Velpatasvir (SOF/VEL) vs Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) and between HCV mono infection and HIV/HCV co infection groups.
Measured: Pre-treatment, after first week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2016 (estimated)
- Study startJan 2017
- Primary completion30 Sep 2019
- Study completion30 Sep 2020
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HCV CoinfectionStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Sulkowski, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02938013
- Sponsor's protocol ID
- IRB00110677
- Acronym
- deLIVER
- Status last verified
- Oct 2020
- First submitted
- 12 Oct 2016
- Last updated
- 24 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sachithanandham J, Leep-Lazar J, Quinn J, Bowden K, Balasubramaniam P, Ward K, Ribeiro RM, Sulkowski MS, Balagopal A. Direct-Acting Antivirals Quickly Eradicate Hepatitis C Virus From the Liver in People With Human Immunodeficiency Virus but Do Not Fully Reverse Immune Activation. J Infect Dis. 2025 Jun 2;231(5):1299-1308. doi: 10.1093/infdis/jiae598.
PubMed 39656808Sachithanandham J, Balagopal A, Leep-Lazar J, Quinn J, Bowden K, Ward K, Ribeiro RM, Sulkowski MS. Second-Phase Hepatitis C Plasma Viral Kinetics Directly Reflects Reduced Intrahepatic Burden of Hepatitis C Virus. J Infect Dis. 2023 Aug 11;228(3):311-320. doi: 10.1093/infdis/jiad025.
PubMed 36722133
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- deLIVER: Direct Acting Antiviral Effects on the Liver
- ClinicalTrials.gov ID
- NCT02938013
- Acronym / sponsor ID
- deLIVER / IRB00110677
- Conditions
- HCV Coinfection, Liver Disease, HIV
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Jan 2017 (actual)
- Primary completion
- 30 Sep 2019 (actual)
- Study completion
- 30 Sep 2020 (actual)
- First posted
- 19 Oct 2016 (estimated)
- Results
- Posted 16 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Open-label, partially-randomized plasma and liver sampling study to assess hepatitis C virus (HCV) kinetics during treatment with two (Sofosbuvir/Velpatasvir) or three (Sofosbuvir/Velpatasvir/Voxilaprevir) direct acting antivirals (DAAs)
Detailed description
Primary Objective: The primary objective is to estimate the 1-week change in the proportion of HCV-infected hepatocytes in participants with HCV monoinfection and HIV/HCV coinfection on therapy with two or three DAAs with different mechanisms of action using single cell laser microdissection (scLCM).
Secondary Objectives:
Estimate the change over the first week in plasma HCV RNA in subjects with HCV monoinfected and HIV/HCV coinfected participants on therapy with two or three DAAs
Estimate the 1 week change in the amount of HCV RNA per infected hepatocyte using scLCM on liver biopsy specimens, obtained just prior to treatment initiation (pre-treatment), and after the first week of DAA therapy.
Estimate the change in the proportion of HCV-infected hepatocytes that express interferon-stimulated genes (ISGs) within the first week of DAA therapy using scLCM.
Measure the change in expression of ISGs in non-parenchymal intrahepatic immune cells (Kupffer cells, plasmacytoid dendritic cells) within the first week of DAA therapy using scLCM.
Exploratory Objectives:
Estimate the 1 week change in expression of ISGs from peripheral blood mononucleated cells (PBMCs) within the first week of DAA+ribavirin (RBV) therapy using scLCM.
Compare sequence(s) of HCV protease, nonstructural protein 5A (NS5A), and nonstructural protein 5B (NS5B) depending on the peripheral sequence) of intrahepatic HCV RNA in single cells and bulk tissue, before and during week 1 of DAA+RBV therapy.
Estimate the week 1 change in the sizes and numbers of HCV-infected clusters on DAA therapy to test whether clearance of HCV-infected hepatocytes occurs in spatially random patterns or within specific clusters.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: Sofosbuvir/Velpatasvir/Voxilaprevir [SOF/VEL/VOX]Monoinfected: Sofosbuvir/Velpatasvir/Voxilaprevir SOF/VEL/VOX days 0-7 Paired liver biopsy at days 0 and 7 (cohort 1) or days 0 and 4 (cohort 2). SOF/VEL days 8 (week 2) through 84 (week 12). Post-treatment follow up through week 12. |
| Group B | Active comparator | Drug: Sofosbuvir/Velpatasvir (SOF/VEL)Monoinfected: Sofosbuvir/Velpatasvir (SOF/VEL) days 0 through 7 and Paired liver biopsy at days 0 and 7 (cohort 1) or days 0 and 4 (cohort 2). SOF/VEL on day 8 (week 2) through 84 (week 12) . Post-Treatment follow up through week 12. |
| Group C | Active comparator | Drug: Sofosbuvir/Velpatasvir (SOF/VEL)HIV/HCV Co-infection: Sofosbuvir/Velpatasvir (SOF/VEL) days 0 through 7 and Paired liver biopsy at days 0 and 7 (cohort 1) or days 0 and 4 (cohort 2). SOF/VEL on day 8 (week 2) through 84 (week 12) . Post-Treatment follow up through week 12. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (25 listed)
- Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:
- Breastfeeding.
- Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.
- Acute or serious illness requiring systemic treatment and/or hospitalization within 42 days prior to study entry.
- Active hepatitis B infection (positive HBsAg) within 42 days prior to study entry.
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/Voxilaprevir [SOF/VEL/VOX]antiviral therapy for HCV | Drug | Group A |
| Sofosbuvir/Velpatasvir (SOF/VEL)antiviral therapy for HCV | Drug | Group B, Group C |
Primary outcome
Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy
Time frame: Pre-treatment, Day 7
Estimate the total number of HCV-infected Hepatocytes (virus burden) for each participant between pre-treatment liver biopsy and post treatment liver biopsy samples using HCV Quantitative real time PCR. Comparison of total number of HCV-infected Hepatocytes (virus burden) were reported between HCV mono infection and co infection groups.
3 secondary outcomes
Reduction Over the First Week in Plasma HCV RNA
Time frame: Pre-treatment, up to 1 week
Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM).
Time frame: Pre-treatment, up to 1 week
Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy.
Time frame: Pre-treatment, after first week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39656808Sachithanandham J, Leep-Lazar J, Quinn J, Bowden K, Balasubramaniam P, Ward K, Ribeiro RM, Sulkowski MS, Balagopal A. Direct-Acting Antivirals Quickly Eradicate Hepatitis C Virus From the Liver in People With Human Immunodeficiency Virus but Do Not Fully Reverse Immune Activation. J Infect Dis. 2025 Jun 2;231(5):1299-1308. doi: 10.1093/infdis/jiae598.
- Derived from this study: PubMed 36722133Sachithanandham J, Balagopal A, Leep-Lazar J, Quinn J, Bowden K, Ward K, Ribeiro RM, Sulkowski MS. Second-Phase Hepatitis C Plasma Viral Kinetics Directly Reflects Reduced Intrahepatic Burden of Hepatitis C Virus. J Infect Dis. 2023 Aug 11;228(3):311-320. doi: 10.1093/infdis/jiad025.
- Individual participant dataSharing planned: No
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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.
Mark Sulkowski, M.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sofosbuvir/Velpatasvir/Voxilaprevir [SOF/VEL/VOX] and Sofosbuvir/Velpatasvir (SOF/VEL) in people with HCV Coinfection and Liver Disease, run by Johns Hopkins University 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 0 inclusion and 25 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 24 Feb 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 16 Nov 2020). 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?
Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy (time frame: Pre-treatment, Day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02938013, which also lists 2 linked publications.
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 24 Feb 2022.