Hepatitis CPhase 4NCT02902120
HCV Treatment Immune Response With Grazoprevir/Elbasvir Before or After Renal Transplant
A Phase 4 study testing Post-transplant Grazoprevir and Elbasvir in people with Hepatitis C and Renal Insufficiency, Chronic, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
The purpose of this study is to determine whether patients treated for chronic hepatitis C (HCV) with zepatier (grazoprevir/elbasvir) prior to kidney transplant will have a stronger immune response compared to patients treated after kidney transplant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C, Renal Insufficiency, Chronic, Disorder of Transplanted Kidney
- What is being tested?
- Post-transplant Grazoprevir and Elbasvir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2017to 8 Jun 2022
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least 18 years of age at the time of screening
- Have stable renal function for one month (30 days) prior to enrollment
- Have Chronic HCV infection prior to transplantation with documented HCV viremia ≥ 1,000 IU/ml at screening and either documented HCV Ab positivity or HCV viremia ≥ 1,000 IU/ml at least 6 months prior to enrollment.
- Documented genotype 1 HCV infection prior to enrollment and after their transplant in the post-transplantation cohort
- HCV disease staging within 12 months prior to enrollment by liver biopsy, transient elastography, or biochemical testing
- Be able to give informed consent and comply with study guidelines
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- Women of childbearing age will be required to have a negative pregnancy test at enrollment and use birth control throughout the duration of treatment.
- Patients will either be:
- On the transplant waiting list followed by the University of Maryland's nephrology clinic or the Baltimore VA's nephrology clinic
- On chronic hemodialysis not yet on the transplant list and followed in the University's hemodialysis center or in the University's nephrology clinic
- Have chronic kidney disease with GFR <50
- Patients will have undergone renal transplantation no greater than five years prior to enrollment and will be followed in our University's nephrology and infectious disease clinic. They will all have stable renal function at the time of enrollment.
Who cannot join
- Documented positive hepatitis B (HBV) surface antigen, and/or HBV DNA prior to enrollment
- Any prior exposure to HCV protease inhibitor therapy
- HIV co-infection if on a protease inhibitor based regimen
- Increase in creatinine of 15% or greater within one month (30 days) of the screening visit
- Evidence of hepatocellular carcinoma at the time of enrollment
- Liver disease caused by an etiology other than HCV
Show all 16Show fewer
- F4 or decompensated cirrhotic patients
- Child Pugh class B or C
- AST or ALT >350 within 6 months prior to enrollment
- Albumin < 3g/dL at the time of enrollment
- Platelet count < 75 at the time of enrollment
- History of clinically significant allergy or adverse event with protease inhibitors
- Evidence of the acquisition of HCV at the time of or after transplantation
- Pregnant or breastfeeding women
- Cyclosporine; St. John's Wort; Efavirenz; Phenytoin; Carbamazepine; Bosentan; HIV protease inhibitors; modafinil; ketoconazole; or rifampin use within 7 days of enrollment
- Coadministration of more than 20 mg atorvastatin; 10 mg rosuvastatin; 20 mg of fluvastatin, lovastatin or simvastatin
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland Medical Center
Baltimore, Maryland, 21201
About this study
Official title: Host Mechanisms Involved in Achieving SVR Using Grazoprevir and Elbasvir in Treatment of Chronic Hepatitis C in Patients With CKD Before and After Renal Transplantation
The purpose of this study is to determine whether patients treated for chronic hepatitis C (HCV) with zepatier (grazoprevir/elbasvir) prior to kidney transplant will have a stronger immune response compared to patients treated after kidney transplant. 25 patients with chronic kidney disease (CKD) and HCV will be treated with zepatier and 25 kidney transplant recipients with chronic kidney disease will be treated with zepatier. Blood markers of immune function will be monitored in both groups to determine their response to therapy.
Read the detailed description
The study will be a pilot, prospective, single-center, open-label, non-randomized, non-controlled, parallel clinical trial. 25 HCV genotype 1 infected patients post transplant will be enrolled in the study. Recruitment will be conducted through the renal transplant and nephrology outpatient clinics at the University of Maryland.
The post-transplant cohort will include renal transplant recipients of both living donor and deceased donor organs infected with HCV prior to their transplantation with GFRs <50 with active HCV viremia. These patients will be recruited from the University of Maryland's multidisciplinary transplant nephrology clinic or infectious disease clinic.
Screening All patients will be screened at the Institute of Human Virology (IHV) Clinical Research Unit. At this visit, all patients will have screening labs drawn and a history and physical examination performed. Additional requirements will be genotype testing prior to enrollment, but after transplant and disease staging within 12 months of enrollment by liver biopsy, elastography, or biochemical testing. For those who do not have a genotype or disease staging within the specified time frame, genotyping and elastography will be repeated as part of the study screening work up. Eligibility will be determined based upon these results within 6 weeks of starting the study drugs.
Given the reduced efficacy of this regimen in patients with genotype 1a with the presence of baseline NS5A resistance-associated variants (RAVs), the investigators will screen patients for RAVs in patients with HCV genotype 1a at the time of enrollment. Any patient with genotype 1a HCV found to have NS5A RAVs will undergo 16 weeks of therapy according to current treatment guidelines.
Starting therapy Study drugs will be administered starting on day 0 after a history and physical examination is performed and safety labs are checked. All patients will sign an informed consent as approved by our Institutional Review Board (IRB) prior to administration of study drugs.
Study visits during treatment Patients will be followed every 4 weeks while they are receiving study drugs. HCV viral load (VL), safety labs and hepatic panel will be performed at each of these visits. Patients will also be advised about study adherence and monitored for adverse events.
Safety and adverse event monitoring At each study visit, research nurses will inquire about adverse events that may or may not be related to study drugs. Any unfavorable medical occurrences will be recorded, whether or not considered related to the patient's participation in the research, temporally associated with the patient's participation in the research. Adverse events (AEs) classified as grade 3 or higher will be reported to the IRB and principal investigator. Any grade 3 or 4 AEs and all serious adverse events (SAEs) will be reviewed as they occur by the study team.
Safety labs will also be drawn at these visits. Levels of immunosuppressive agents will also be determined at these visits as appropriate. The need for dose modification of the patient's immunosuppression in the time between visits will be recorded.
End of treatment visit Patients will be seen 12 weeks after starting study drugs (or 16 weeks in the case of genotype 1a patients with baseline NS5A RAVs) for an end of study visit. HCV VL, safety labs and hepatic panel will be performed at this visit. Patients will also be counseled about study adherence and the investigators will inquire about adverse events.
Post treatment follow up visits Patients will be followed every 4 weeks for 12 weeks after they complete treatment. HCV VL, safety labs and a hepatic panel will be performed at these visits.
- Being tested
- Post-transplant Grazoprevir and Elbasvir
- Medical subject headings
- Hepatitis C, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Post-transplant Grazoprevir and ElbasvirDrug
Also called Zepatier
Treatment will be started in the post-transplant patients on day 0 with the combination pill zepatier, containing grazoprevir 100mg/elbasvir 50mg by mouth once daily. The medications will be continued for a total of 12 weeks (16 weeks if resistance mutations, RAVs, are detected)
| Study group | Role | What they receive |
|---|---|---|
| Post-transplant | Experimental | This arm will evaluate the treatment of patients with HCV and chronic kidney disease (GFR <50) who have had a kidney transplant using grazoprevir and elbasvir. Receives: Drug: Post-transplant Grazoprevir and Elbasvir |
What is being measured
The primary outcome is the main question the study is designed to answer.
SVR 12
Sustained virologic response (SVR) will be assessed by measuring the quantitative HCV viral load 12 weeks after completing treatment. This will be a measure of circulating HCV virus in participants off therapy, 12 weeks after finishing treatment, to determine the durability of the response to the treatment.
Measured: This will be measured at post-treatment week 12 (study week 24 or week 28 for those with resistance mutations)
Secondary outcomes (6)
Change in T Cell Response
The study will involve measuring the change in T cell response by analyzing the frequency of exhaustion markers PD-1 and activation markers ICOS, CD38, CD69 at day 0, week 4, and week 12.
Measured: This will be collected at day 0, week 4, and week 12
Change in T Cell Immunophenotypes
The study will involve measuring the change in T cell immunophenotypes
Measured: This will be collected at day 0, week 4, and week 12
Quantification of Antiviral Cytokines
The study will involve measuring interferon gamma and TNF alpha levels
Measured: This will be collected at day 0 and week 4
Safety as Assessed by Adverse Event Monitoring, Including Routine Lab Work
Safety will be assessed by adverse event monitoring, including routine lab work
Measured: This will be measured at day 0, weeks 2, 4, 8, 12 (and 16 if resistance mutations are present)
Kidney Function
Clinical review using labs and the patient's chart will be performed for change in kidney graft function by change in eGFR or creatinine
Measured: This will be measured at day 0, treatment week 2, treatment week 4, treatment week 8, treatment week 12, ( treatment week 16, if applicable), post-treatment week 4 (week 16/20), and post-treatment week 12 (week 24/28)
Kidney Allograft Rejection
Clinical review using labs and the patient's chart will be performed for documented episodes of kidney rejection
Measured: This will be measured at post-treatment week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2016 (estimated)
- Study start1 May 2017
- Primary completion1 Sep 2021
- Study completion8 Jun 2022
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 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jennifer Husson, University of Maryland, Baltimore
- Investigators
- Jennifer S Husson, MD, Principal investigator, University of Maryland School of Medicine, Institute of Human Virology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02902120
- Sponsor's protocol ID
- HP-00071069
- Status last verified
- Apr 2024
- First submitted
- 19 Aug 2016
- Last updated
- 22 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported, after deidentification will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Host Mechanisms Involved in Achieving SVR Using Grazoprevir and Elbasvir in Treatment of Chronic Hepatitis C in Patients With CKD Before and After Renal Transplantation
- ClinicalTrials.gov ID
- NCT02902120
- Acronym / sponsor ID
- HP-00071069
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- 1 May 2017 (actual)
- Primary completion
- 1 Sep 2021 (actual)
- Study completion
- 8 Jun 2022 (actual)
- First posted
- 15 Sep 2016 (estimated)
- Results
- Posted 18 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether patients treated for chronic hepatitis C (HCV) with zepatier (grazoprevir/elbasvir) prior to kidney transplant will have a stronger immune response compared to patients treated after kidney transplant. 25 patients with chronic kidney disease (CKD) and HCV will be treated with zepatier and 25 kidney transplant recipients with chronic kidney disease will be treated with zepatier. Blood markers of immune function will be monitored in both groups to determine their response to therapy.
Detailed description
The study will be a pilot, prospective, single-center, open-label, non-randomized, non-controlled, parallel clinical trial. 25 HCV genotype 1 infected patients post transplant will be enrolled in the study. Recruitment will be conducted through the renal transplant and nephrology outpatient clinics at the University of Maryland.
The post-transplant cohort will include renal transplant recipients of both living donor and deceased donor organs infected with HCV prior to their transplantation with GFRs <50 with active HCV viremia. These patients will be recruited from the University of Maryland's multidisciplinary transplant nephrology clinic or infectious disease clinic.
Screening All patients will be screened at the Institute of Human Virology (IHV) Clinical Research Unit. At this visit, all patients will have screening labs drawn and a history and physical examination performed. Additional requirements will be genotype testing prior to enrollment, but after transplant and disease staging within 12 months of enrollment by liver biopsy, elastography, or biochemical testing. For those who do not have a genotype or disease staging within the specified time frame, genotyping and elastography will be repeated as part of the study screening work up. Eligibility will be determined based upon these results within 6 weeks of starting the study drugs.
Given the reduced efficacy of this regimen in patients with genotype 1a with the presence of baseline NS5A resistance-associated variants (RAVs), the investigators will screen patients for RAVs in patients with HCV genotype 1a at the time of enrollment. Any patient with genotype 1a HCV found to have NS5A RAVs will undergo 16 weeks of therapy according to current treatment guidelines.
Starting therapy Study drugs will be administered starting on day 0 after a history and physical examination is performed and safety labs are checked. All patients will sign an informed consent as approved by our Institutional Review Board (IRB) prior to administration of study drugs.
Study visits during treatment Patients will be followed every 4 weeks while they are receiving study drugs. HCV viral load (VL), safety labs and hepatic panel will be performed at each of these visits. Patients will also be advised about study adherence and monitored for adverse events.
Safety and adverse event monitoring At each study visit, research nurses will inquire about adverse events that may or may not be related to study drugs. Any unfavorable medical occurrences will be recorded, whether or not considered related to the patient's participation in the research, temporally associated with the patient's participation in the research. Adverse events (AEs) classified as grade 3 or higher will be reported to the IRB and principal investigator. Any grade 3 or 4 AEs and all serious adverse events (SAEs) will be reviewed as they occur by the study team.
Safety labs will also be drawn at these visits. Levels of immunosuppressive agents will also be determined at these visits as appropriate. The need for dose modification of the patient's immunosuppression in the time between visits will be recorded.
End of treatment visit Patients will be seen 12 weeks after starting study drugs (or 16 weeks in the case of genotype 1a patients with baseline NS5A RAVs) for an end of study visit. HCV VL, safety labs and hepatic panel will be performed at this visit. Patients will also be counseled about study adherence and the investigators will inquire about adverse events.
Post treatment follow up visits Patients will be followed every 4 weeks for 12 weeks after they complete treatment. HCV VL, safety labs and a hepatic panel will be performed at these visits.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Post-transplant | Experimental | Drug: Post-transplant Grazoprevir and ElbasvirThis arm will evaluate the treatment of patients with HCV and chronic kidney disease (GFR <50) who have had a kidney transplant using grazoprevir and elbasvir. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- At least 18 years of age at the time of screening
- Have stable renal function for one month (30 days) prior to enrollment
- Have Chronic HCV infection prior to transplantation with documented HCV viremia ≥ 1,000 IU/ml at screening and either documented HCV Ab positivity or HCV viremia ≥ 1,000 IU/ml at least 6 months prior to enrollment.
- Documented genotype 1 HCV infection prior to enrollment and after their transplant in the post-transplantation cohort
- HCV disease staging within 12 months prior to enrollment by liver biopsy, transient elastography, or biochemical testing
Key exclusion criteria (16 listed)
- Documented positive hepatitis B (HBV) surface antigen, and/or HBV DNA prior to enrollment
- Any prior exposure to HCV protease inhibitor therapy
- HIV co-infection if on a protease inhibitor based regimen
- Increase in creatinine of 15% or greater within one month (30 days) of the screening visit
- Evidence of hepatocellular carcinoma at the time of enrollment
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 |
|---|---|---|
| Post-transplant Grazoprevir and ElbasvirAlso: ZepatierTreatment will be started in the post-transplant patients on day 0 with the combination pill zepatier, containing grazoprevir 100mg/elbasvir 50mg by mouth once daily. The medications will be continued for a total of 12 weeks (16 weeks if resistance mutations, RAVs, are detected) | Drug | Post-transplant |
Primary outcome
SVR 12
Time frame: This will be measured at post-treatment week 12 (study week 24 or week 28 for those with resistance mutations)
Sustained virologic response (SVR) will be assessed by measuring the quantitative HCV viral load 12 weeks after completing treatment. This will be a measure of circulating HCV virus in participants off therapy, 12 weeks after finishing treatment, to determine the durability of the response to the treatment.
6 secondary outcomes
Change in T Cell Response
Time frame: This will be collected at day 0, week 4, and week 12
Change in T Cell Immunophenotypes
Time frame: This will be collected at day 0, week 4, and week 12
Quantification of Antiviral Cytokines
Time frame: This will be collected at day 0 and week 4
Safety as Assessed by Adverse Event Monitoring, Including Routine Lab Work
Time frame: This will be measured at day 0, weeks 2, 4, 8, 12 (and 16 if resistance mutations are present)
Kidney Function
Time frame: This will be measured at day 0, treatment week 2, treatment week 4, treatment week 8, treatment week 12, ( treatment week 16, if applicable), post-treatment week 4 (week 16/20), and post-treatment week 12 (week 24/28)
Kidney Allograft Rejection
Time frame: This will be measured at post-treatment week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported, after deidentification will be shared.
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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.
Jennifer S Husson, MD principal investigator
University of Maryland School of Medicine, Institute of Human Virology
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 Post-transplant Grazoprevir and Elbasvir in people with Hepatitis C and Renal Insufficiency, Chronic, 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 12 inclusion and 16 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 22 Apr 2024. 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 18 Nov 2022). 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?
SVR 12 (time frame: This will be measured at post-treatment week 12 (study week 24 or week 28 for those with resistance mutations)). 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 22 Apr 2024.