Kidney TransplantEarly Phase 1NCT03249194
Hepatitis C Virus Donor Positive Kidney Transplantation for Hepatitis C Virus Negative Recipients
A Early Phase 1 study testing Direct acting Anti-Viral Therapy using Epclusa or Zepatier in people with Kidney Transplant and Hepatitis C, run by Virginia Commonwealth University at 1 site in United States.
Trial summary
The development of direct acting anti-virals (DAAs) for the treatment of Hepatitis C virus (HCV) has changed the landscape of HCV therapy dramatically in the last several years with reported sustained virologic response (SVR) rates in excess of 95% for treatment-naïve HCV positive patients including those who have… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Kidney Transplant, Hepatitis C
- What is being tested?
- Direct acting Anti-Viral Therapy using Epclusa or Zepatier
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Aug 2017to 15 Mar 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- No evidence of HCV infection by HCV PCR (done at the time of the initial consent)
- Age>60 yrs with an expected waiting time>2 years; or
- Age<60 yrs with any one of the following risk factors: Diabetes, coronary artery disease, peripheral artery disease and/or cerebrovascular disease
- Willingness to provide informed consent
- Absence of a living donor.
Who cannot join
- Estimated life expectancy of less than one year based on clinical judgment of the investigator
- Prior liver or renal transplantation
- Pregnant women
- Incarcerated patients
- Medical or social condition which in the opinion of the investigator will interfere with or prevent follow-up per protocol
- Unable or unwilling to return for follow-up visits
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- Donor Exclusion Criteria:
- HBV sAg positive
- HIV PCR or antibody positive
- HCV RNA negative
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
Official title: Hepatitis C Virus Donor Positive Kidney Transplantation for Hepatitis C Virus Negative Recipients: A Trial of Ultra-short Duration Direct Acting Anti-viral Prophylaxis To Prevent Virus Transmission From Hepatitis C Viremic Donors To Hepatitis C Negative Kidney Transplant Recipients (DAPPER)
The development of direct acting anti-virals (DAAs) for the treatment of Hepatitis C virus (HCV) has changed the landscape of HCV therapy dramatically in the last several years with reported sustained virologic response (SVR) rates in excess of 95% for treatment-naïve HCV positive patients including those who have received liver or kidney transplants. Since these new regimens do not include interferon and have already been studied in the post-liver and kidney transplant setting, they now offer a unique opportunity to expand the donor pool and improve the lives of those awaiting renal transplant. The address this gap in knowledge, the investigators hypothesize that pre-emptive treatment with a direct acting anti-viral HCV medication to cure HCV soon after transplant would allow for safe transplantation of HCV positive kidneys in disadvantaged and needy HCV negative kidney recipients with acceptable risks and improved survivals compared with historical cohorts.
Read the detailed description
Traditionally, HCV+ kidneys are not offered to HCV- patients on the waiting list. The primary concern with offering HCV+ kidneys to HCV- recipients is a risk of viral transmission. Although data about the long-term impact of HCV+ kidney transplantation in to HCV- recipients is unclear, there was a clear suggestion of an increased risk of liver disease in these patients based upon studies performed in the 1990s. Traditional therapy with Interferon could not be offered to these patients as it can lead of rejection if kidney transplant. It was recently reported that nearly 65% (out of a total 6546) of all HCV+ kidneys were discarded between the years 2005-2014. These kidneys were otherwise of excellent quality and could have benefitted more than 4000 patients with 12,000 plus years of graft life.
Since the recent FDA approval of Direct Acting Anti-virals (DAA), these drugs have now been shown to be safe and efficacious even in the setting of kidney transplant. They could offer a unique opportunity to expand the kidney donor pool. For this study, the investigators hypothesize that pre-emptive treatment with a direct acting anti-viral HCV medication to cure HCV soon after transplant would allow for safe transplantation of HCV+ kidneys in disadvantaged and needy HCV- kidney recipients with acceptable risks and improved survivals compared with historical cohorts. This novel study will develop pilot data on the safety and efficacy of utilizing HCV+ kidneys in high-risk HCV- recipients in order to expand the donor pool and reduce the morbidity and mortality of hemodialysis.
- Conditions
- Kidney Transplant, Hepatitis C
- Being tested
- Direct acting Anti-Viral Therapy using Epclusa or Zepatier
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Direct acting Anti-Viral Therapy using Epclusa or ZepatierDrug
Also called Epclusa, Zepatier
All patients will receive one 'on-call' dose of SOFOSBUVIR/VELPATASVIR (Epclusa, Gilead) immediately prior to transplant and one dose on post-operative Day 1 post-transplant. Patients who develop detectable HCV viremia will be initiated on Direct Acting Anti-viral (DAA) therapy between 2-4 weeks post-transplant. Patients with GT1 will be treated with ELBASVIR/GRAZOPREVIR (Zepatier, Merck) and those with GT2 or 3 will be treated with SOFOSBUVIR/VELPATASVIR (Epclusa, Gilead) based upon donor genotyping results
| Study group | Role | What they receive |
|---|---|---|
| HCV+ Donor Kidney Recipient | Experimental | All HCV- participants who receive an HCV+ donor kidney transplant will receive a first 'on-call' dose of Epclusa (sofosbuvir/velpatasvir; Gilead) and then three more doses on post-operative Day 1, 2 and 3. Donor HCV Genotype data will be available by Day 7 of transplant.
Patients will then be followed by serial HCV PCRs. Patients who are HCV PCR positive by Day 14 will be treated with Epclusa once daily x 12 weeks. Receives: Drug: Direct acting Anti-Viral Therapy using Epclusa or Zepatier |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained Virologic Response (SVR)
Among the patients who develop HCV viremia SVR rates with DAA will be measured
Measured: 12 weeks
Graft and Patient Survival
Age and co-morbidity will matched historical HCV- recipients as controls. Patient survival will also be compared to a contemporary cohort of wait listed patients who declined enrollment due to personal choice
Measured: 1 year
Secondary outcomes (3)
Sustained Virologic Response (SVR) Follow Up 1
Among the patients who develop HCV viremia SVR rates with DAA will be measured
Measured: 24 weeks
Sustained Virologic Response (SVR) Follow Up 2
Among the patients who develop HCV viremia SVR rates with DAA will be measured
Measured: 48 weeks
Liver Disease
Among patients who develop HCV viremia liver disease progression will be measured using non-invasive panels like fibroscan
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2017
- Study start17 Aug 2017
- Primary completion15 Mar 2020
- Study completion15 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Kidney TransplantStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gaurav Gupta, MD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03249194
- Sponsor's protocol ID
- HM20010320
- Status last verified
- Mar 2020
- First submitted
- 9 Aug 2017
- Last updated
- 27 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Gupta G, Yakubu I, Bhati CS, Zhang Y, Kang L, Patterson JA, Andrews-Joseph A, Alam A, Ferreira-Gonzalez A, Kumar D, Moinuddin IK, Kamal L, King AL, Levy M, Sharma A, Cotterell A, Reichman TW, Khan A, Kimball P, Stiltner R, Baldecchi M, Brigle N, Gehr T, Sterling RK. Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients. Am J Transplant. 2020 Mar;20(3):739-751. doi: 10.1111/ajt.15664. Epub 2019 Nov 15.
PubMed 31652392
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hepatitis C Virus Donor Positive Kidney Transplantation for Hepatitis C Virus Negative Recipients: A Trial of Ultra-short Duration Direct Acting Anti-viral Prophylaxis To Prevent Virus Transmission From Hepatitis C Viremic Donors To Hepatitis C Negative Kidney Transplant Recipients (DAPPER)
- ClinicalTrials.gov ID
- NCT03249194
- Acronym / sponsor ID
- HM20010320
- Conditions
- Kidney Transplant, Hepatitis C
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Study start
- 17 Aug 2017 (actual)
- Primary completion
- 15 Mar 2020 (actual)
- Study completion
- 15 Mar 2020 (actual)
- First posted
- 15 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The development of direct acting anti-virals (DAAs) for the treatment of Hepatitis C virus (HCV) has changed the landscape of HCV therapy dramatically in the last several years with reported sustained virologic response (SVR) rates in excess of 95% for treatment-naïve HCV positive patients including those who have received liver or kidney transplants. Since these new regimens do not include interferon and have already been studied in the post-liver and kidney transplant setting, they now offer a unique opportunity to expand the donor pool and improve the lives of those awaiting renal transplant. The address this gap in knowledge, the investigators hypothesize that pre-emptive treatment with a direct acting anti-viral HCV medication to cure HCV soon after transplant would allow for safe transplantation of HCV positive kidneys in disadvantaged and needy HCV negative kidney recipients with acceptable risks and improved survivals compared with historical cohorts.
Detailed description
Traditionally, HCV+ kidneys are not offered to HCV- patients on the waiting list. The primary concern with offering HCV+ kidneys to HCV- recipients is a risk of viral transmission. Although data about the long-term impact of HCV+ kidney transplantation in to HCV- recipients is unclear, there was a clear suggestion of an increased risk of liver disease in these patients based upon studies performed in the 1990s. Traditional therapy with Interferon could not be offered to these patients as it can lead of rejection if kidney transplant. It was recently reported that nearly 65% (out of a total 6546) of all HCV+ kidneys were discarded between the years 2005-2014. These kidneys were otherwise of excellent quality and could have benefitted more than 4000 patients with 12,000 plus years of graft life.
Since the recent FDA approval of Direct Acting Anti-virals (DAA), these drugs have now been shown to be safe and efficacious even in the setting of kidney transplant. They could offer a unique opportunity to expand the kidney donor pool. For this study, the investigators hypothesize that pre-emptive treatment with a direct acting anti-viral HCV medication to cure HCV soon after transplant would allow for safe transplantation of HCV+ kidneys in disadvantaged and needy HCV- kidney recipients with acceptable risks and improved survivals compared with historical cohorts. This novel study will develop pilot data on the safety and efficacy of utilizing HCV+ kidneys in high-risk HCV- recipients in order to expand the donor pool and reduce the morbidity and mortality of hemodialysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HCV+ Donor Kidney Recipient | Experimental | Drug: Direct acting Anti-Viral Therapy using Epclusa or ZepatierAll HCV- participants who receive an HCV+ donor kidney transplant will receive a first 'on-call' dose of Epclusa (sofosbuvir/velpatasvir; Gilead) and then three more doses on post-operative Day 1, 2 and 3. Donor HCV Genotype data will be available by Day 7 of transplant. Patients will then be followed by serial HCV PCRs. Patients who are HCV PCR positive by Day 14 will be treated with Epclusa once daily x 12 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- No evidence of HCV infection by HCV PCR (done at the time of the initial consent)
- Age>60 yrs with an expected waiting time>2 years; or
- Age<60 yrs with any one of the following risk factors: Diabetes, coronary artery disease, peripheral artery disease and/or cerebrovascular disease
- Willingness to provide informed consent
- Absence of a living donor.
Key exclusion criteria (10 listed)
- Estimated life expectancy of less than one year based on clinical judgment of the investigator
- Prior liver or renal transplantation
- Pregnant women
- Incarcerated patients
- Medical or social condition which in the opinion of the investigator will interfere with or prevent follow-up per protocol
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 |
|---|---|---|
| Direct acting Anti-Viral Therapy using Epclusa or ZepatierAlso: Epclusa, ZepatierAll patients will receive one 'on-call' dose of SOFOSBUVIR/VELPATASVIR (Epclusa, Gilead) immediately prior to transplant and one dose on post-operative Day 1 post-transplant. Patients who develop detectable HCV viremia will be initiated on Direct Acting Anti-viral (DAA) therapy between 2-4 weeks post-transplant. Patients with GT1 will be treated with ELBASVIR/GRAZOPREVIR (Zepatier, Merck) and those with GT2 or 3 will be treated with SOFOSBUVIR/VELPATASVIR (Epclusa, Gilead) based upon donor genotyping results | Drug | HCV+ Donor Kidney Recipient |
Primary outcome
Sustained Virologic Response (SVR)
Time frame: 12 weeks
Among the patients who develop HCV viremia SVR rates with DAA will be measured
Graft and Patient Survival
Time frame: 1 year
Age and co-morbidity will matched historical HCV- recipients as controls. Patient survival will also be compared to a contemporary cohort of wait listed patients who declined enrollment due to personal choice
3 secondary outcomes
Sustained Virologic Response (SVR) Follow Up 1
Time frame: 24 weeks
Sustained Virologic Response (SVR) Follow Up 2
Time frame: 48 weeks
Liver Disease
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2020.
- Derived from this study: PubMed 31652392Gupta G, Yakubu I, Bhati CS, Zhang Y, Kang L, Patterson JA, Andrews-Joseph A, Alam A, Ferreira-Gonzalez A, Kumar D, Moinuddin IK, Kamal L, King AL, Levy M, Sharma A, Cotterell A, Reichman TW, Khan A, Kimball P, Stiltner R, Baldecchi M, Brigle N, Gehr T, Sterling RK. Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients. Am J Transplant. 2020 Mar;20(3):739-751. doi: 10.1111/ajt.15664. Epub 2019 Nov 15.
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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.
Gaurav Gupta, MD principal investigator
Virginia Commonwealth University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Direct acting Anti-Viral Therapy using Epclusa or Zepatier in people with Kidney Transplant and Hepatitis C, run by Virginia Commonwealth 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 5 inclusion and 10 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 27 Mar 2020. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Sustained Virologic Response (SVR) (time frame: 12 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?
On the ClinicalTrials.gov record for NCT03249194, which also lists 1 linked publication.
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 27 Mar 2020.