Once-daily Regimen With Envarsus® to Optimize Immunosuppression Management and Outcomes in Kidney Transplant Recipients

Study Overview
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Brief Summary
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With the availability of well-studied once-daily formulations of tacrolimus, the ability to achieve a true once-daily immunosuppressant regimen along with everolimus and steroids may finally be achievable and have the potential to optimize immunosuppression safety and efficacy in kidney transplantation.

Detailed Description
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A once-daily immunosuppressant regimen comprising of Envarsus-everolimus-prednisone will have 6-month treatment failure rates that are non-inferior to the twice-daily regimen of Envarsus-mycophenolate mofetil-prednisone and will have improved patient-reported adherence.

Official Title
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Once-daily Regimen With Envarsus® to Optimize Immunosuppression Management and Outcomes in Kidney Transplant Recipients

Conditions
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Immunosuppression

Intervention / Treatment
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* Drug: Tacrolimus
* Drug: Prednisone
* Drug: Mycophenolate mofetil
* Drug: Everolimus


Participation Criteria
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Eligibility Criteria
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1. Inclusion criteria Male or female adult (≥18 years old) with a history of solitary kidney transplant within 3 months (±2 months) of transplant with self-reported medication adherence issues, as indicated by a MMAS-8 of at least 1. Patients must be capable of understanding the purposes and risks of the study and have the ability to give written informed consent and be willing to participate and comply with the study. Women of childbearing potential must have a negative pregnancy test within the 48 hours prior to receiving study medication. Women of childbearing potential and sexually active males must be willing to use contraception, as indicated in Section 6 of the protocol. Subjects who are not of reproductive potential (status post bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or vasectomy), not sexually active, whose current partner(s) is not of reproductive potential, or whose sexual activity is exclusively homosexual are eligible without requiring the use of contraception. 2. Exclusion criteria Patients will be excluded if they are pregnant or nursing females or males with a pregnant female partner Recipient of multiple organ transplant Recipient of a non-renal organ Proteinuria > 800 mg/24 hour eGFR < 30 ml/min WBC ≤ 2k/mm3 Plt ≤ 50k/mm3 Triglycerides > 500 mg/dL HIV positive (HIV ab +) Unable to tolerate oral medications Use of another investigational product within thirty days prior to receiving study medication Acute graft rejection within the past month (Banff 1A or higher) or received an ABO incompatible donor organ. A condition or disorder that, in the opinion of the investigator, may adversely affect the outcome of the study or the safety of the subject

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tacrolimus + MMF<br>Tacrolimus IR BID (5-12ng/mL) + mycophenolate mofetil 1g BID + prednisone x at least 3 months, then converted to Tacrolimus Daily (5 -12ng/mL) + mycophenolate mofetil 1g BID + prednisone x 6 months | Drug: Tacrolimus<br>* goal trough level 5-12ng/mL<br>* Other names: Envarsus;Drug: Prednisone<br>* goal dose 5mg QD<br>* Other names: Methylprednisolone;Drug: Mycophenolate mofetil<br>* goal dose 1g BID<br>|
| Active Comparator: Envarsus + Everolimus<br>Tacrolimus IR BID (5-12ng/mL) + mycophenolate mofetil 1g BID + prednisone x at least 3 months, then converted to Envarsus Daily (2-5ng/mL) + Everolimus Daily (3-8ng/mL) + prednisone x 6 months | Drug: Tacrolimus<br>* goal trough level 5-12ng/mL<br>* Other names: Envarsus;Drug: Prednisone<br>* goal dose 5mg QD<br>* Other names: Methylprednisolone;Drug: Everolimus<br>* goal trough level 3-8ng/mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-reported Medication Adherence From Baseline to 6 Months. | Percent of subjects reporting high medication adherence at baseline compared to 6 months post-conversion, using the Morisky Medication Adherence scale (MMAS). The MMAS rates medication adherence on a scale of 0 to 8. 0 is high adherence, 1-2 is medium adherence, and greater than or equal to 3 is low adherence. | 6 months post conversion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants Experiencing Acute Allograft Rejection | Estimate the composite of treatment failure rate, defined as acute allograft rejection with a Banff grade 1A or higher, graft loss, or death at six months post-conversion, in patients converted to a once-daily immunosuppressant regimen of Envarsus®, everolimus, and prednisone versus patients converted to a twice-daily regimen of Envarsus®, MMF, and prednisone. | Baseline to 6 months post conversion |