End Stage Renal DiseasePhase 3NCT03289650

Extended Release Tacrolimus vs. Twice-Daily Tacrolimus

A Phase 3 study testing Tacrolimus and Tacrolimus Extended Release Oral Tablet [Envarsus] in people with End Stage Renal Disease and Rejection of Renal Transplant, run by Lorenzo Gallon at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The overall aim of the study is to prospectively investigate the impact of two maintenance calcineurin inhibitor immunosuppressive regimens: once-daily extended release tacrolimus and twice-daily tacrolimus on subpopulations of T and B cells and alloreactive T cells as well as on renal allograft function. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: End Stage Renal Disease, Rejection of Renal Transplant
What is being tested?: Tacrolimus and Tacrolimus Extended Release Oral Tablet [Envarsus]
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 29 participants
Where: 1 siteUnited States
Study dates: 5 Sep 2017to 23 Feb 2021
Phase: Phase 3
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

1. Patients who are males or females aged 18-65 years. 2. Use of the following induction medications: basiliximab and rituximab. 2. Donors aged 18-65 years. 3. No prior organ transplant 4. Patients who are single-organ recipients (kidney only). 5. Women who are of childbearing potential must have a negative serum pregnancy test before transplantation and agree to use a medically acceptable method of contraception throughout the treatment period.
6. Subject (recipient) is able to understand the consent form and give written informed consent

Who cannot join

Delayed graft function (please see above).
Known sensitivity or contraindication to alemtuzumab, Envarsus® XR, tacrolimus or MMF.
Use of the following induction medications: basiliximab and rituximab
Patient with significant or active infection.
Patients with a positive flow cytometric crossmatch using donor lymphocytes and recipient serum.
Patients with PRA > 40%

Show all 23Show fewer

Patients with current or historic donor specific antibodies
Body Mass Index (BMI) of < 18 or > 35
Patients who are pregnant or nursing mothers.
Patients whose life expectancy is severely limited by diseases other than renal disease.
Ongoing active substance abuse, drug or alcohol.
Major ongoing psychiatric illness or recent history of noncompliance.
Significant cardiovascular disease (e.g.):
Significant non-correctable coronary artery disease;
Ejection fraction below 30%;
History of recent myocardial infarction.
Malignancy within 3 years, excluding non-melanoma skin cancers.
Serologic evidence of infection with HIV or HBVs-Ag positive.
Patients with a screening/baseline total white blood cell count < 4,000/mm3; platelet count < 100,000/mm3; triglyceride > 400 mg/dl; total cholesterol > 300 mg/dl.
Investigational drug within 30 days prior to transplant surgery.
Anti-T cell therapy within 30 days prior to transplant surgery.
Diagnosis of atypical-Hemolytic Uremic Syndrome (aHUS).
Subjects transplanted with a Hepatitis C NAT-positive kidney.

Trial locations and contacts

1 site in 1 country.

United States1 site

Northwestern University
Chicago, Illinois, 60611

Other trials in United States

About this study

Official title: Once-Daily Extended-Release Tacrolimus vs. Twice-Daily Tacrolimus: Impact on T-Cell Subpopulations and Markers of Renal Tubule-toxicity in Kidney Transplant Patients

Read the detailed description

Kidney transplantation is the treatment of choice for most patients with end-stage renal disease. Lifelong immunosuppressive therapies are required to prevent organ rejection. However, long term exposure to immunosuppressive therapy after kidney transplantation can place patients at risk for multiple adverse events. The optimal immunosuppressive therapy is not well established. Tacrolimus, a calcineurin inhibitor (CNI) is highly effective in preventing acute rejection after organ transplantation (2). It is used as part of the immunosuppression regimen for the majority of kidney and liver transplant recipients (3). However, treatment with current formulation of Tacrolimus generates high peaks and low troughs in drug concentrations in the blood. It is known that high exposure to CNI is associated with renal toxicities and adverse events (4). New once-daily dosage formulations are now developed with the hope of minimizing side effects while maintaining excellent outcomes (5-8).

LCP-Tacro (Envarsus® XR, Veloxis Pharmaceuticals), a new once-daily formulation of tacrolimus, was approved by the FDA in 2015 for conversion from twice-daily tacrolimus in kidney transplant recipients. It is a prolonged-release tacrolimus formulation, utilizing a MeltDose drug delivery technology designed to improve the bioavailability of drugs with low water solubility (1). Recent clinical data demonstrated that once-daily LCP-Tacro has improved pharmacokinetic bioavailability, rapid achievement of therapeutic trough levels, less fluctuation and swing in whole blood concentration, non-inferior efficacy and similar safety, with lower tacrolimus dose than other tacrolimus formulations.

The target population is adult recipients of immediately functioning living and deceased donor renal allografts. Immediate function will be defined as the absence of the need for hemodialysis in the first week following renal transplantation.

Prospective randomized single center open label study of 2 groups of kidney transplant patients

Group 1 : standard of care (SOC) control group will receive tacrolimus twice-daily (n=25)
Group 2 : LCP-Tacro (Envarsus® XR) group will receive LCPT tablets once daily (n=25)

Conditions: End Stage Renal Disease, Rejection of Renal Transplant
Being tested: Tacrolimus, Tacrolimus Extended Release Oral Tablet [Envarsus]
Keywords: immunosuppression
Medical subject headings: Kidney Failure, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TacrolimusDrug
immunosuppressive agent tacrolimus, given twice-daily
Tacrolimus Extended Release Oral Tablet [Envarsus]Drug
Also called LCP-tacro
immunosuppressive agent extended-release tacrolimus, given once daily

Study groups in NCT03289650
Study group	Role	What they receive
Standard of care tacrolimus twice-daily	Active comparator	Not described Receives: Drug: Tacrolimus
Extended-release tacrolimus once-daily	Active comparator	Not described Receives: Drug: Tacrolimus Extended Release Oral Tablet [Envarsus]

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Kidney Transplant Function From 2 Weeks Post Transplant Through 12 Months Post Transplant
change in the mean eGFR from the baseline (2 weeks post transplant), 3 months (post transplant) , and 12 months (post transplant).
Measured: 2 weeks post transplant through 12 months post transplant

Secondary outcomes (5)

Change in Subpopulations of T Cells From 2 Weeks Post Transplant Through 12 Months Post Transplant
Blood, urine and kidney tissue analysis via serial flow cytometric immunophenotyping (includes regulatory T and B cell populations as well as immune functions).
Measured: Measured at 2 weeks post transplant, 3 months post transplant, 12 months post transplant
Number of Participants With Acute Rejection at 3 Months and 12 Months Post-Transplant
Acute rejection of kidney transplant is determined via biopsy.
Measured: Measured at 3 months post transplant, 12 months post transplant
Number of Participants With Graft Loss at 3 Months and 12 Months Post-Transplant
Graft loss is determined via biopsy.
Measured: Measured at 3 months post transplant, 12 months post transplant
Number of Subjects Deceased at at 3 Months and 12 Months Post-Transplant
Subject survival status is continually monitored via routine follow-up visits.
Measured: Through 12 months post transplant
Number of Participants With Change in Allograft Immunohistopathology Profile
Tissue analysis via immunohistopathological staining and microscopic examination Moderate acute tubular necrosis => presence of focal coagulative necrosis or infarction on histopathologic examination
Arteriolar hyalinosis grade 2 means: Replacement of degenerated smooth muscle cells by hyaline deposits in more than 1 arteriole, without circumferential involvement
Global glomerulosclerosis >grade 2, means glomerulosclerosis affecting more than 50% of glomeruli in the biopsy sample
IFTA : Interstitial fibrosis and tubular atrophy: Inflammation in 26% to 50% of scarred cortical parenchyma
Measured: Measured at 3 months post transplant, 12 months post transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Sep 201723 Feb 2021

First posted21 Sep 2017
Study start5 Sep 2017
Primary completion23 Feb 2021
Study completion23 Feb 2021

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 End Stage Renal DiseaseStudies 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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03289650
Sponsor's protocol ID: STU00205327
Status last verified: Mar 2023
First submitted: 12 Sep 2017
Last updated: 10 Apr 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All End Stage Renal Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Once-Daily Extended-Release Tacrolimus vs. Twice-Daily Tacrolimus: Impact on T-Cell Subpopulations and Markers of Renal Tubule-toxicity in Kidney Transplant Patients
ClinicalTrials.gov ID: NCT03289650
Acronym / sponsor ID: STU00205327
Conditions: End Stage Renal Disease, Rejection of Renal Transplant
Keywords: immunosuppression
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 29 participants (actual)
Lead sponsor: Lorenzo GallonUniversity, hospital or other
Study start: 5 Sep 2017 (actual)
Primary completion: 23 Feb 2021 (actual)
Study completion: 23 Feb 2021 (actual)
First posted: 21 Sep 2017 (actual)
Results: Posted 10 Apr 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Prospective randomized single center open label study of 2 groups of kidney transplant patients

Group 1 : standard of care (SOC) control group will receive tacrolimus twice-daily (n=25)
Group 2 : LCP-Tacro (Envarsus® XR) group will receive LCPT tablets once daily (n=25)

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Standard of care tacrolimus twice-daily	Active comparator	Drug: Tacrolimus
Extended-release tacrolimus once-daily	Active comparator	Drug: Tacrolimus Extended Release Oral Tablet [Envarsus]

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

1. Patients who are males or females aged 18-65 years. 2. Use of the following induction medications: basiliximab and rituximab. 2. Donors aged 18-65 years. 3. No prior organ transplant 4. Patients who are single-organ recipients (kidney only). 5. Women who are of childbearing potential must have a negative serum pregnancy test before transplantation and agree to use a medically acceptable method of contraception throughout the treatment period.
6. Subject (recipient) is able to understand the consent form and give written informed consent

Key exclusion criteria (23 listed)

Delayed graft function (please see above).
Known sensitivity or contraindication to alemtuzumab, Envarsus® XR, tacrolimus or MMF.
Use of the following induction medications: basiliximab and rituximab
Patient with significant or active infection.
Patients with a positive flow cytometric crossmatch using donor lymphocytes and recipient serum.

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
Tacrolimusimmunosuppressive agent tacrolimus, given twice-daily	Drug	Standard of care tacrolimus twice-daily
Tacrolimus Extended Release Oral Tablet [Envarsus]Also: LCP-tacroimmunosuppressive agent extended-release tacrolimus, given once daily	Drug	Extended-release tacrolimus once-daily

Primary outcome

Change in Kidney Transplant Function From 2 Weeks Post Transplant Through 12 Months Post Transplant
Time frame: 2 weeks post transplant through 12 months post transplant
change in the mean eGFR from the baseline (2 weeks post transplant), 3 months (post transplant) , and 12 months (post transplant).

5 secondary outcomes

Change in Subpopulations of T Cells From 2 Weeks Post Transplant Through 12 Months Post Transplant
Time frame: Measured at 2 weeks post transplant, 3 months post transplant, 12 months post transplant
Number of Participants With Acute Rejection at 3 Months and 12 Months Post-Transplant
Time frame: Measured at 3 months post transplant, 12 months post transplant
Number of Participants With Graft Loss at 3 Months and 12 Months Post-Transplant
Time frame: Measured at 3 months post transplant, 12 months post transplant
Number of Subjects Deceased at at 3 Months and 12 Months Post-Transplant
Time frame: Through 12 months post transplant
Number of Participants With Change in Allograft Immunohistopathology Profile
Time frame: Measured at 3 months post transplant, 12 months post transplant

Results and safety

Results posted to the registry on 10 Apr 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group 1: Control Arm: Standard of Care (SOC) Tacrolimus	14	14
Group 2: Interventional Arm: Study Related Drug: LCP-Tacrolimus/Envarsus XR (LCP-Tacro/Envarsus XR)	15	15

Primary outcome: Change in Kidney Transplant Function From 2 Weeks Post Transplant Through 12 Months Post Transplant

Time frame: 2 weeks post transplant through 12 months post transplant. Mean (Standard Error). Unit: mL/min/1.73m^2

Measure	Group 1: Control Arm: Standard of Care (SOC) Tacrolimus n = 14	Group 2: Interventional Arm: Study Related Drug: LCP-Tacrolimus/Envarsus XR (LCP-Tacro/Envarsus XR) n = 15
Value	2.03 (1.71)	-2.19 (1.77)

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were reviewed at 1 year after tranplant. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Standard of Care Tacrolimus Twice-daily	0 of 14 (0%)	7 of 14 (50%)	0 of 14
Extended-release Tacrolimus Once-daily	1 of 15 (6.7%)	5 of 15 (33.3%)	0 of 15

Limitations and caveats (from the sponsor): The study ran out of funding and as a result the outcome (Change in Subpopulations of T Cells) has not been analyzed. The PI will look for additional funding to complete the analysis

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Recruiting
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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.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 2 inclusion and 23 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 Apr 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 10 Apr 2023). 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?

Change in Kidney Transplant Function From 2 Weeks Post Transplant Through 12 Months Post Transplant (time frame: 2 weeks post transplant through 12 months post transplant). 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 NCT03289650.

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 Apr 2023; AzTrials last refreshed its copy on 26 Oct 2026.