Kidney Transplant; ComplicationsPhase 1NCT03438773
Prospective Pilot Feasibility Study Comparing Envarsus Once-a-day to Tacrolimus Twice-a-day Immunosuppressive Regimen on Drug Bioavailability in Hispanic First Time Kidney Transplant Recipients
A Phase 1 study testing Envarsus and Tacrolimus in people with Kidney Transplant; Complications and Kidney Transplant Failure and Rejection, run by California Institute of Renal Research at 1 site in United States.
Trial summary
This investigator-initiated post-marketing study will evaluate the role of Hispanic ethnicity on drug dosing of Envarsus in first-time stable renal transplant recipients. Tacrolimus trough drug levels will be studied as a primary endpoint at 24 hours after drug dosing and at steady state (e.g., trough level at 3… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplant; Complications, Kidney Transplant Failure and Rejection
- What is being tested?
- Envarsus and Tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Jul 2018to Dec 2023
- Phase
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or Female 18 years of age or older.
- The subject is a first time stable renal transplant patients, who have received their transplant at least 3 months before study entry.
- The subject is willing to commit to the study design.
- The subject is considered to have stable allograft function defined as no documented rejection episodes within one month of screening.
- The subject is not currently receiving treatment with other experimental therapies directed at their transplant.
Who cannot join
- The subject has undergone a prior organ or bone marrow transplant.
- The subject has taken any interacting/contraindicated drug determined by the Investigator within 30 days of administration of the protocol.
- Any study drug allergies and if there are high serum donor specific antibody levels (DSA) or a high panel reactive antibody level (PRA).
- Documented treatment of rejection within 30 days of onset of the screening visit.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
California Institute of Renal Research
San Diego, California, 92123
Eva Gripp, LVN, 858-637-4600, EGripp@balboaunited.org
Karina Maldonado, 858-810-8083, KMaldonado@balboaunited.org
About this study
This investigator-initiated post-marketing study will evaluate the role of Hispanic ethnicity on drug dosing of Envarsus in first-time stable renal transplant recipients. Tacrolimus trough drug levels will be studied as a primary endpoint at 24 hours after drug dosing and at steady state (e.g., trough level at 3 months post conversion) and secondary compliance assessments will be done by pill counts at clinic visits. Secondary outcomes will be the safety of once a day dosing as well as assessment of graft rejection and graft failure. In addition, concentration/dose ratios will be analyzed. The results of this study will provide important information about dosing of once a day tacrolimus (Envarsus) in Hispanic kidney transplant patients, which represents the largest growing group of patients with End-Stage Renal Disease
Read the detailed description
Adequate drug dosing is essential to prevent allograft rejection and subsequent allograft loss. Many studies have shown that serum levels of immunosuppressant medications can be strongly influenced by the patient's genetic profile. Genetics has been shown to influence tacrolimus drug dosing in both liver and kidney transplant recipients 1. Whether these genetic differences influence care in clinical practice though is not known. Several genetic influences have been identified in Hispanic patients, such as polymorphisms in Cytochrome genes 1 and Nuclear Factor-kappa B genes 2, that might influence tacrolimus dosing and blood levels. In a study of Hispanic children, significant correlations were found to suggest that ethnic differences resulted in the need for higher or more frequent tacrolimus doing in Hispanic children 3. According to the Centers for Disease Control, Hispanics are 1.5 times as likely as non-Hispanic whites to develop ESRD 4 and Hispanics are the largest minority with the fastest growth of ESRD in the United States 5. Therefore it is likely that the unanswered question of whether there are differences in bioavailability of Envarsus in Hispanic patients will become even more relevant over time. Strategies that target improved bioavailability have the opportunity to significantly improve outcomes for all recipients of kidney transplants. Specifically, vulnerable patient populations, such as Hispanic patients, need to be studied to better understand the potential for altered bioavailability of immunosuppressive medications based on inherited pharmacologic traits.
Providing patients a once-a-day option for their immunosuppressive medication dosing is predicted to improve adherence, but whether once daily Envarsus provides adequate drug levels in Hispanic patient groups is not known. This study will carefully evaluate drug levels as a primary endpoint in this investigator-initiated study. Additional secondary outcomes to be measured over the two years of the study will be allograft rejection and allograft loss. The hypothesis of this study is that kidney transplant recipients receiving once-a-day extended release tacrolimus (Envarsus) will have outcomes that are not inferior to those who received twice-a-day tacrolimus during the two-year study period.
- Being tested
- Envarsus, Tacrolimus
- Keywords
- Hispanic, First time kidney recipients
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnvarsusDrug
Patients randomized into the Envarsus group will be prescribed Envarsus, mycophenolate and prednisone once daily.
TacrolimusDrug
Patients randomized to the Tacrolimus group will be prescribed Tacrolimus twice-daily with standard of care immunosuppression, anti-proliferative and prednisone once-daily.
| Study group | Role | What they receive |
|---|---|---|
| Envarsus | Other | Study group - Envarsus once daily in addition to standard of care. Receives: Drug: Envarsus |
| Tacrolimus | Other | Control group - Tacrolimus twice daily in addition to standard of care. Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tacrolimus drug levels
Tacrolimus trough drug levels will be studied as a primary endpoint at 24 hours after drug dosing and at steady state through local lab HPLC MS/MS assays.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2018
- Study start11 Jul 2018
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney Transplant; ComplicationsStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients randomized into the study group will be prescribed Envarsus, mycophenolate and prednisone as a regimen vs. standard therapy with twice a day tacrolimus, mycophenolate and prednisone. Patients randomized to the control group will be prescribed standard immunosuppression with tacrolimus twice a day, anti-proliferative twice a day, and prednisone once a day at doses that are standard at our institution.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- California Institute of Renal Research
- Sponsor type
- University, hospital or other
- Collaborators
- Balboa Institute of Transplantation, University of California, San Diego
- Responsible party
- Sponsor
- Investigators
- Arman Faravardeh, MD, Principal investigator, California Institute of Renal Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03438773
- Sponsor's protocol ID
- VLX001-17
- Other IDs
- v01 01-Sep-2017
- Status last verified
- Feb 2023
- First submitted
- 1 Dec 2017
- Last updated
- 9 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Pilot Feasibility Study Comparing Envarsus Once-a-day to Tacrolimus Twice-a-day Immunosuppressive Regimen on Drug Bioavailability in Hispanic First Time Kidney Transplant Recipients
- ClinicalTrials.gov ID
- NCT03438773
- Acronym / sponsor ID
- VLX001-17
- Keywords
- Hispanic, First time kidney recipients
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- California Institute of Renal ResearchUniversity, hospital or other
- Collaborators
- Balboa Institute of Transplantation, University of California, San Diego
- Study start
- 11 Jul 2018 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 20 Feb 2018 (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.
This investigator-initiated post-marketing study will evaluate the role of Hispanic ethnicity on drug dosing of Envarsus in first-time stable renal transplant recipients. Tacrolimus trough drug levels will be studied as a primary endpoint at 24 hours after drug dosing and at steady state (e.g., trough level at 3 months post conversion) and secondary compliance assessments will be done by pill counts at clinic visits. Secondary outcomes will be the safety of once a day dosing as well as assessment of graft rejection and graft failure. In addition, concentration/dose ratios will be analyzed. The results of this study will provide important information about dosing of once a day tacrolimus (Envarsus) in Hispanic kidney transplant patients, which represents the largest growing group of patients with End-Stage Renal Disease
Detailed description
Adequate drug dosing is essential to prevent allograft rejection and subsequent allograft loss. Many studies have shown that serum levels of immunosuppressant medications can be strongly influenced by the patient's genetic profile. Genetics has been shown to influence tacrolimus drug dosing in both liver and kidney transplant recipients 1. Whether these genetic differences influence care in clinical practice though is not known. Several genetic influences have been identified in Hispanic patients, such as polymorphisms in Cytochrome genes 1 and Nuclear Factor-kappa B genes 2, that might influence tacrolimus dosing and blood levels. In a study of Hispanic children, significant correlations were found to suggest that ethnic differences resulted in the need for higher or more frequent tacrolimus doing in Hispanic children 3. According to the Centers for Disease Control, Hispanics are 1.5 times as likely as non-Hispanic whites to develop ESRD 4 and Hispanics are the largest minority with the fastest growth of ESRD in the United States 5. Therefore it is likely that the unanswered question of whether there are differences in bioavailability of Envarsus in Hispanic patients will become even more relevant over time. Strategies that target improved bioavailability have the opportunity to significantly improve outcomes for all recipients of kidney transplants. Specifically, vulnerable patient populations, such as Hispanic patients, need to be studied to better understand the potential for altered bioavailability of immunosuppressive medications based on inherited pharmacologic traits.
Providing patients a once-a-day option for their immunosuppressive medication dosing is predicted to improve adherence, but whether once daily Envarsus provides adequate drug levels in Hispanic patient groups is not known. This study will carefully evaluate drug levels as a primary endpoint in this investigator-initiated study. Additional secondary outcomes to be measured over the two years of the study will be allograft rejection and allograft loss. The hypothesis of this study is that kidney transplant recipients receiving once-a-day extended release tacrolimus (Envarsus) will have outcomes that are not inferior to those who received twice-a-day tacrolimus during the two-year study period.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients randomized into the study group will be prescribed Envarsus, mycophenolate and prednisone as a regimen vs. standard therapy with twice a day tacrolimus, mycophenolate and prednisone. Patients randomized to the control group will be prescribed standard immunosuppression with tacrolimus twice a day, anti-proliferative twice a day, and prednisone once a day at doses that are standard at our institution.
| Arm | Type | Receives |
|---|---|---|
| Envarsus | Other | Drug: EnvarsusStudy group - Envarsus once daily in addition to standard of care. |
| Tacrolimus | Other | Drug: TacrolimusControl group - Tacrolimus twice daily in addition to standard of care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or Female 18 years of age or older.
- The subject is a first time stable renal transplant patients, who have received their transplant at least 3 months before study entry.
- The subject is willing to commit to the study design.
- The subject is considered to have stable allograft function defined as no documented rejection episodes within one month of screening.
- The subject is not currently receiving treatment with other experimental therapies directed at their transplant.
Key exclusion criteria (4 listed)
- The subject has undergone a prior organ or bone marrow transplant.
- The subject has taken any interacting/contraindicated drug determined by the Investigator within 30 days of administration of the protocol.
- Any study drug allergies and if there are high serum donor specific antibody levels (DSA) or a high panel reactive antibody level (PRA).
- Documented treatment of rejection within 30 days of onset of the screening visit.
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 |
|---|---|---|
| EnvarsusPatients randomized into the Envarsus group will be prescribed Envarsus, mycophenolate and prednisone once daily. | Drug | Envarsus |
| TacrolimusPatients randomized to the Tacrolimus group will be prescribed Tacrolimus twice-daily with standard of care immunosuppression, anti-proliferative and prednisone once-daily. | Drug | Tacrolimus |
Primary outcome
Tacrolimus drug levels
Time frame: 2 years
Tacrolimus trough drug levels will be studied as a primary endpoint at 24 hours after drug dosing and at steady state through local lab HPLC MS/MS assays.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2023.
- Individual participant dataSharing planned: Undecided
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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.
Arman Faravardeh, MD principal investigator
California Institute of Renal Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Envarsus and Tacrolimus in people with Kidney Transplant; Complications and Kidney Transplant Failure and Rejection, run by California Institute of Renal Research 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 4 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: status not confirmed, as of the sponsor's last update on 9 Feb 2023. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michael C Gastauer (858-810-8155, mgastauer@balboaunited.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tacrolimus drug levels (time frame: 2 years). 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 9 Feb 2023.