Immunosuppression
Conditions
Brief summary
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
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.
Interventions
DRUGTacrolimus
goal trough level 5-12ng/mL
DRUGPrednisone
goal dose 5mg QD
DRUGMycophenolate mofetil
goal dose 1g BID
DRUGEverolimus
goal trough level 3-8ng/mL
Sponsors
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1\. Inclusion criteria 1. 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. 2. 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. 3. Women of childbearing potential must have a negative pregnancy test within the 48 hours prior to receiving study medication. 4. 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
1. Patients will be excluded if they are pregnant or nursing females or males with a pregnant female partner 2. Recipient of multiple organ transplant 3. Recipient of a non-renal organ 4. Proteinuria \> 800 mg/24 hour 5. eGFR \< 30 ml/min 6. WBC ≤ 2k/mm3 7. Plt ≤ 50k/mm3 8. Triglycerides \> 500 mg/dL 9. HIV positive (HIV ab +) 10. Unable to tolerate oral medications 11. Use of another investigational product within thirty days prior to receiving study medication 12. Acute graft rejection within the past month (Banff 1A or higher) or received an ABO incompatible donor organ. 13. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Self-reported Medication Adherence From Baseline to 6 Months. | 6 months post conversion | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Experiencing Acute Allograft Rejection | Baseline to 6 months post conversion | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subject Specific Change on Medication Side Effect Scale | Baseline to 6 months post conversion | Examine subject specific change on a validated Medication Side Effect Scale at the time of the conversion versus six months post-conversion, compared between the two arms. Side effect burden scale is from 0 to 180. A lower score is less side effect burden, a higher score is more side effect burden. |
| Percent of Participants Who Experienced Kidney Transplant Graft Loss | Baseline to 6 months post conversion | Measure and compare time-to-event analysis between the two arms graft loss (time to event analysis) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control: Envarsus + MMF Envarsus Daily (5 -12ng/mL) + mycophenolate mofetil 1g BID + prednisone x 6 months
Tacrolimus: goal trough level 5-12ng/mL
Prednisone: goal dose 5mg QD
Mycophenolate mofetil: goal dose 1g BID | 20 |
| Intervention: Envarsus + Everoliumus Envarsus Daily (2-5ng/mL) + Everolimus Daily (3-8ng/mL) + prednisone x 6 months
Tacrolimus: goal trough level 2-5 ng/mL
Prednisone: goal dose 5mg QD
Everolimus: goal trough level 3-8ng/mL | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Intervention: Envarsus + Everoliumus | Control: Envarsus + MMF | Total |
|---|---|---|---|
| Age, Continuous | 50.3 years STANDARD_DEVIATION 14.4 | 52.4 years STANDARD_DEVIATION 12.9 | 51.3 years STANDARD_DEVIATION 13.5 |
| Percent of Participants with Medicare Insurance | 16 Participants | 14 Participants | 30 Participants |
| Primary Reason for End Stage Renal Disease Diabetes | 7 Participants | 6 Participants | 13 Participants |
| Primary Reason for End Stage Renal Disease FSGS | 1 Participants | 3 Participants | 4 Participants |
| Primary Reason for End Stage Renal Disease Hypertension | 5 Participants | 4 Participants | 9 Participants |
| Primary Reason for End Stage Renal Disease IgA Nephropathy | 1 Participants | 2 Participants | 3 Participants |
| Primary Reason for End Stage Renal Disease Lupus | 1 Participants | 0 Participants | 1 Participants |
| Primary Reason for End Stage Renal Disease Other | 3 Participants | 3 Participants | 6 Participants |
| Primary Reason for End Stage Renal Disease Polycystic Kidney Disease | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 8 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 12 Participants | 22 Participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 27 Participants |
| Weight | 88.3 kg STANDARD_DEVIATION 14.1 | 89.7 kg STANDARD_DEVIATION 15.5 | 89.0 kg STANDARD_DEVIATION 14.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 8 / 20 | 9 / 20 |
| serious Total, serious adverse events | 1 / 20 | 1 / 20 |
Outcome results
Primary
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.
Time frame: 6 months post conversion
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control: Envarsus + MMF | Self-reported Medication Adherence From Baseline to 6 Months. | Baseline | 80 % of participants |
| Control: Envarsus + MMF | Self-reported Medication Adherence From Baseline to 6 Months. | 6 months post-conversion | 59 % of participants |
| Intervention: Envarsus + Everoliumus | Self-reported Medication Adherence From Baseline to 6 Months. | Baseline | 45 % of participants |
| Intervention: Envarsus + Everoliumus | Self-reported Medication Adherence From Baseline to 6 Months. | 6 months post-conversion | 47 % of participants |
Secondary
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.
Time frame: Baseline to 6 months post conversion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control: Envarsus + MMF | Percent of Participants Experiencing Acute Allograft Rejection | 0 Participants |
| Intervention: Envarsus + Everoliumus | Percent of Participants Experiencing Acute Allograft Rejection | 0 Participants |
Other Pre-specified
Percent of Participants Who Experienced Kidney Transplant Graft Loss
Measure and compare time-to-event analysis between the two arms graft loss (time to event analysis)
Time frame: Baseline to 6 months post conversion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control: Envarsus + MMF | Percent of Participants Who Experienced Kidney Transplant Graft Loss | 0 Participants |
| Intervention: Envarsus + Everoliumus | Percent of Participants Who Experienced Kidney Transplant Graft Loss | 0 Participants |
Other Pre-specified
Subject Specific Change on Medication Side Effect Scale
Examine subject specific change on a validated Medication Side Effect Scale at the time of the conversion versus six months post-conversion, compared between the two arms. Side effect burden scale is from 0 to 180. A lower score is less side effect burden, a higher score is more side effect burden.
Time frame: Baseline to 6 months post conversion
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control: Envarsus + MMF | Subject Specific Change on Medication Side Effect Scale | Baseline | 71 units on a scale | Standard Deviation 67 |
| Control: Envarsus + MMF | Subject Specific Change on Medication Side Effect Scale | 6 month post-conversion | 93 units on a scale | Standard Deviation 86 |
| Intervention: Envarsus + Everoliumus | Subject Specific Change on Medication Side Effect Scale | Baseline | 37 units on a scale | Standard Deviation 38 |
| Intervention: Envarsus + Everoliumus | Subject Specific Change on Medication Side Effect Scale | 6 month post-conversion | 38 units on a scale | Standard Deviation 34 |