Trial Outcomes & Findings for Once-daily Regimen With Envarsus® to Optimize Immunosuppression Management and Outcomes in Kidney Transplant Recipients (NCT NCT02954198)

Last Updated: 2019-12-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

40 participants

Primary outcome timeframe

6 months post conversion

Results posted on

2019-12-24

Participant Flow

Participant milestones

Participant milestones
Measure	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	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
Overall Study STARTED	20	20
Overall Study COMPLETED	20	20
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Control: Envarsus + MMF n=20 Participants 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	Intervention: Envarsus + Everoliumus n=20 Participants 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	Total n=40 Participants Total of all reporting groups
Age, Continuous	52.4 years STANDARD_DEVIATION 12.9 • n=5 Participants	50.3 years STANDARD_DEVIATION 14.4 • n=7 Participants	51.3 years STANDARD_DEVIATION 13.5 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Percent of Participants with Medicare Insurance	14 Participants n=5 Participants	16 Participants n=7 Participants	30 Participants n=5 Participants
Weight	89.7 kg STANDARD_DEVIATION 15.5 • n=5 Participants	88.3 kg STANDARD_DEVIATION 14.1 • n=7 Participants	89.0 kg STANDARD_DEVIATION 14.6 • n=5 Participants
Primary Reason for End Stage Renal Disease Diabetes	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Primary Reason for End Stage Renal Disease Hypertension	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Primary Reason for End Stage Renal Disease Polycystic Kidney Disease	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Primary Reason for End Stage Renal Disease FSGS	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Primary Reason for End Stage Renal Disease IgA Nephropathy	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Primary Reason for End Stage Renal Disease Lupus	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Primary Reason for End Stage Renal Disease Other	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months post conversion

Outcome measures

Outcome measures
Measure	Control: Envarsus + MMF n=20 Participants 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	Intervention: Envarsus + Everoliumus n=20 Participants 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
Self-reported Medication Adherence From Baseline to 6 Months. Baseline	80 % of participants	45 % of participants
Self-reported Medication Adherence From Baseline to 6 Months. 6 months post-conversion	59 % of participants	47 % of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Control: Envarsus + MMF n=20 Participants 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	Intervention: Envarsus + Everoliumus n=20 Participants 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
Percent of Participants Experiencing Acute Allograft Rejection	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Control: Envarsus + MMF n=20 Participants 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	Intervention: Envarsus + Everoliumus n=20 Participants 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
Subject Specific Change on Medication Side Effect Scale Baseline	71 units on a scale Standard Deviation 67	37 units on a scale Standard Deviation 38
Subject Specific Change on Medication Side Effect Scale 6 month post-conversion	93 units on a scale Standard Deviation 86	38 units on a scale Standard Deviation 34

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 6 months post conversion

Measure and compare time-to-event analysis between the two arms graft loss (time to event analysis)

Outcome measures

Outcome measures
Measure	Control: Envarsus + MMF n=20 Participants 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	Intervention: Envarsus + Everoliumus n=20 Participants 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
Percent of Participants Who Experienced Kidney Transplant Graft Loss	0 Participants	0 Participants

Adverse Events

Control: Envarsus + MMF

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Intervention: Envarsus + Everoliumus

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Control: Envarsus + MMF n=20 participants at risk 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	Intervention: Envarsus + Everoliumus n=20 participants at risk 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
Infections and infestations JC virus induced Progressive Multifocal Leukoencephalopathy	5.0% 1/20 • Number of events 1 • 6 months from Baseline to end of study.	0.00% 0/20 • 6 months from Baseline to end of study.
Renal and urinary disorders Perinephric fluid collection	0.00% 0/20 • 6 months from Baseline to end of study.	5.0% 1/20 • Number of events 1 • 6 months from Baseline to end of study.

Other adverse events

Other adverse events
Measure	Control: Envarsus + MMF n=20 participants at risk 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	Intervention: Envarsus + Everoliumus n=20 participants at risk 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
Infections and infestations Cytomegalovirus infection	10.0% 2/20 • Number of events 2 • 6 months from Baseline to end of study.	5.0% 1/20 • Number of events 1 • 6 months from Baseline to end of study.
Renal and urinary disorders Borderline kidney rejection	5.0% 1/20 • Number of events 1 • 6 months from Baseline to end of study.	5.0% 1/20 • Number of events 1 • 6 months from Baseline to end of study.
Renal and urinary disorders Interstitial Fibrosis and Tubular Atrophy	10.0% 2/20 • Number of events 2 • 6 months from Baseline to end of study.	10.0% 2/20 • Number of events 2 • 6 months from Baseline to end of study.
Infections and infestations BK infection	5.0% 1/20 • Number of events 1 • 6 months from Baseline to end of study.	5.0% 1/20 • Number of events 1 • 6 months from Baseline to end of study.
Immune system disorders Lymphocele	0.00% 0/20 • 6 months from Baseline to end of study.	5.0% 1/20 • Number of events 1 • 6 months from Baseline to end of study.
Skin and subcutaneous tissue disorders Diabetic foot ulcer	0.00% 0/20 • 6 months from Baseline to end of study.	5.0% 1/20 • Number of events 1 • 6 months from Baseline to end of study.
Investigations Neutropenia	5.0% 1/20 • Number of events 1 • 6 months from Baseline to end of study.	0.00% 0/20 • 6 months from Baseline to end of study.
Renal and urinary disorders Graft dysfunction	0.00% 0/20 • 6 months from Baseline to end of study.	5.0% 1/20 • Number of events 1 • 6 months from Baseline to end of study.
Cardiac disorders Cardiovascular Event	5.0% 1/20 • Number of events 1 • 6 months from Baseline to end of study.	5.0% 1/20 • Number of events 1 • 6 months from Baseline to end of study.

Additional Information

Dr. David Taber

Medical University of South Carolina

Phone: 843-792-4003

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place