Mycophenolic Acid Monotherapy in Recipients of HLA-identical Living-Related Transplantation

• Sponsor: University of Wisconsin, Madison (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01053221
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 77
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This randomized trial will enroll adult recipients of HLA-identical living kidney transplants who are at least 1 year post-transplant. All subjects will be taking Prograf (tacrolimus) or cyclosporine and mycophenolic acid (CellCept or Myfortic) and then be randomized (1:2) to either continue calcineurin inhibitors or to taper off of calcineurin inhibitors. The hypothesis is that mycophenolic acid monotherapy permits long-term rejection-free renal allograft function in the absence of long-term calcineurin inhibitors in this fully matched renal transplant cohort.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplantation	Drug: Mycophenolic Acid; Drug: Standard of Care: CNI and MPA	Phase 2

Detailed Description

The objective of the study is to safely move HLA-identical renal transplant recipients from 2 immunosuppressive drugs (calcineurin inhibitor and mycophenolic acid) to mycophenolic acid monotherapy. Safety will be assessed by monitoring renal function in subjects in the withdrawal group compared to those who remain on the standard 2-drug immunosuppression protocol. Results of immunological monitors such as DTH regulation in response to donor minor antigens and development of anti-donor antibodies will be correlated with successful withdrawal.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Mycophenolic Acid Monotherapy in Recipients of HLA-identical Living-Related Transplantation
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MPA monotherapy Subjects will discontinue calcineurin inhibitor (cyclosporine or tacrolimus) and remain on MPA (mycophenolate mofetil or mycophenolate sodium) monotherapy	Drug: Mycophenolic Acid; Mycophenolate mofetil: 750mg po bid x 36 months OR mycophenolate sodium 540mg po bid x 36 months; Other Names: cellcept, myfortic
Active Comparator: Control: MPA and CNI Subjects will continue with their current immunosuppressive regimen of MPA (mycophenolate mofetil or mycophenolate sodium) and calcineurin inhibitor (cyclosporine or tacrolimus)	Drug: Standard of Care: CNI and MPA; Tacrolimus or cyclosporine: dosed according to trough levels per standard of care Mycophenolate mofetil 750mg po bid or mycophenolate sodium 540mg po bid x 36 months

Outcome Measures

Primary Outcome Measures

1. Incidence of Kidney Allograft Rejection and Graft Loss [36 months]

Secondary Outcome Measures

1. Renal Function Measured by Serum Creatinine and eGFR [36 months]

2. Number of Incidences of Infection and Malignancy [36 months]

   Number of incidences of infection and malignancy will be reported.

3. Patient Survival [36 months]

   patient survival

4. Trans-vivo Delayed Type Hypersensitivity (DTH) Assay [36 months]

   Delayed type hypersensitivity (DTH) reactivity status to donor and minor antigens will be detected using trans-vivo DTH assay. This information will help determine if T-regulatory cells are present, and whether such cells predict outcome of Calcineurin inhibitor withdrawal.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female subjects 18-75 years of age.

• Subjects who are recipients of HLA-identical living donor renal allografts from a sibling and are at least 1 year post transplant, their donors and mothers.

• Subjects must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.

Exclusion Criteria:

• GFR <40ml/min;

• diagnosis of SLE,

• Subjects with proteinuria (defined as a protein:creatinine ratio of >1 or an amount less than this deemed significant on an individual subject basis by the principal investigator),,

• multi-organ transplant;

• known hypersensitivity to, Prograf, Neoral, CellCept or Myfortic;

• history of documented post transplant non-compliance with medications, transplant clinic or laboratory follow-up;

• therapy with an investigational immunosuppressive drug within 6 weeks of study entry;

• history of a psychological illness or condition such as to interfere with the patient's ability to understand the requirements of the study;

• patients on less than 500 mg PO BID of CellCept or 360 mg PO BID of Myfortic at the time of potential randomization,

• history of humoral rejection post transplant,

• maintenance or for cause treatment with steroids (prednisone) within 3 months of enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Wisconsin	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• University of Wisconsin, Madison

Investigators

• Principal Investigator: William Burlingham, PhD, University of Wisconsin, Madison
• Principal Investigator: Hans Sollinger, MD, PhD, University of Wisconsin, Madison

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT01053221
• Other Study ID Numbers: H-2005-0357; 2012-0343
• First Posted: Jan 21, 2010
• Last Update Posted: Jul 5, 2019
• Last Verified: Jun 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Wisconsin, Madison: mycophenolate; living donor
• Additional relevant MeSH terms: Mycophenolic Acid

Study Results

Participant Flow

Pre-assignment Detail	Out of 16 enrolled participants,1 participant never got randomized and 1 participant did not show up for any of the appointments. Only 14 started in the study.

Arm/Group Title	MPA Monotherapy	Control: MPA and CNI
Arm/Group Description	Subjects will discontinue calcineurin inhibitor (cyclosporine or tacrolimus) and remain on MPA (mycophenolate mofetil or mycophenolate sodium) monotherapy Mycophenolic Acid: Mycophenolate mofetil: 750mg po bid x 36 months OR mycophenolate sodium 540mg po bid x 36 months	Subjects will continue with their current immunosuppressive regimen of MPA (mycophenolate mofetil or mycophenolate sodium) and calcineurin inhibitor (cyclosporine or tacrolimus) Standard of Care: CNI and MPA: Tacrolimus or cyclosporine: dosed according to trough levels per standard of care Mycophenolate mofetil 750mg po bid or mycophenolate sodium 540mg po bid x 36 months
Period Title: Overall Study
STARTED	5	9
COMPLETED	0	0
NOT COMPLETED	5	9

Baseline Characteristics

Arm/Group Title	MPA Monotherapy	Control: MPA and CNI	Total
Arm/Group Description	Subjects will discontinue calcineurin inhibitor (cyclosporine or tacrolimus) and remain on MPA (mycophenolate mofetil or mycophenolate sodium) monotherapy Mycophenolic Acid: Mycophenolate mofetil: 750mg po bid x 36 months OR mycophenolate sodium 540mg po bid x 36 months	Subjects will continue with their current immunosuppressive regimen of MPA (mycophenolate mofetil or mycophenolate sodium) and calcineurin inhibitor (cyclosporine or tacrolimus) Standard of Care: CNI and MPA: Tacrolimus or cyclosporine: dosed according to trough levels per standard of care Mycophenolate mofetil 750mg po bid or mycophenolate sodium 540mg po bid x 36 months	Total of all reporting groups
Overall Participants	5	9	14
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 80%	8 88.9%	12 85.7%
>=65 years	1 20%	1 11.1%	2 14.3%
Sex: Female, Male (Count of Participants)
Female	1 20%	2 22.2%	3 21.4%
Male	4 80%	7 77.8%	11 78.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 22.2%	2 14.3%
Not Hispanic or Latino	4 80%	6 66.7%	10 71.4%
Unknown or Not Reported	1 20%	1 11.1%	2 14.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	5 100%	7 77.8%	12 85.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 22.2%	2 14.3%
Region of Enrollment (participants) [Number]
United States	5 100%	9 100%	14 100%

Outcome Measures

1. Primary Outcome

Title	Incidence of Kidney Allograft Rejection and Graft Loss
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

The study was closed prematurely. Data were not collected

Arm/Group Title	MPA Monotherapy	Control: MPA and CNI
Arm/Group Description	Subjects will discontinue calcineurin inhibitor (cyclosporine or tacrolimus) and remain on MPA (mycophenolate mofetil or mycophenolate sodium) monotherapy Mycophenolic Acid: Mycophenolate mofetil: 750mg po bid x 36 months OR mycophenolate sodium 540mg po bid x 36 months	Subjects will continue with their current immunosuppressive regimen of MPA (mycophenolate mofetil or mycophenolate sodium) and calcineurin inhibitor (cyclosporine or tacrolimus) Standard of Care: CNI and MPA: Tacrolimus or cyclosporine: dosed according to trough levels per standard of care Mycophenolate mofetil 750mg po bid or mycophenolate sodium 540mg po bid x 36 months
Measure Participants	0	0

2. Secondary Outcome

Title	Renal Function Measured by Serum Creatinine and eGFR
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

The study was closed prematurely. No data was collected

Arm/Group Title	MPA Monotherapy	Control: MPA and CNI
Arm/Group Description	Subjects will discontinue calcineurin inhibitor (cyclosporine or tacrolimus) and remain on MPA (mycophenolate mofetil or mycophenolate sodium) monotherapy Mycophenolic Acid: Mycophenolate mofetil: 750mg po bid x 36 months OR mycophenolate sodium 540mg po bid x 36 months	Subjects will continue with their current immunosuppressive regimen of MPA (mycophenolate mofetil or mycophenolate sodium) and calcineurin inhibitor (cyclosporine or tacrolimus) Standard of Care: CNI and MPA: Tacrolimus or cyclosporine: dosed according to trough levels per standard of care Mycophenolate mofetil 750mg po bid or mycophenolate sodium 540mg po bid x 36 months
Measure Participants	0	0

3. Secondary Outcome

Title	Number of Incidences of Infection and Malignancy
Description	Number of incidences of infection and malignancy will be reported.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

The study was closed prematurely. No data was collected

Arm/Group Title	MPA Monotherapy	Control: MPA and CNI
Arm/Group Description	Subjects will discontinue calcineurin inhibitor (cyclosporine or tacrolimus) and remain on MPA (mycophenolate mofetil or mycophenolate sodium) monotherapy Mycophenolic Acid: Mycophenolate mofetil: 750mg po bid x 36 months OR mycophenolate sodium 540mg po bid x 36 months	Subjects will continue with their current immunosuppressive regimen of MPA (mycophenolate mofetil or mycophenolate sodium) and calcineurin inhibitor (cyclosporine or tacrolimus) Standard of Care: CNI and MPA: Tacrolimus or cyclosporine: dosed according to trough levels per standard of care Mycophenolate mofetil 750mg po bid or mycophenolate sodium 540mg po bid x 36 months
Measure Participants	0	0

4. Secondary Outcome

Title	Patient Survival
Description	patient survival
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

The study was closed prematurely. Data were not collected

Arm/Group Title	MPA Monotherapy	Control: MPA and CNI
Arm/Group Description	Subjects will discontinue calcineurin inhibitor (cyclosporine or tacrolimus) and remain on MPA (mycophenolate mofetil or mycophenolate sodium) monotherapy Mycophenolic Acid: Mycophenolate mofetil: 750mg po bid x 36 months OR mycophenolate sodium 540mg po bid x 36 months	Subjects will continue with their current immunosuppressive regimen of MPA (mycophenolate mofetil or mycophenolate sodium) and calcineurin inhibitor (cyclosporine or tacrolimus) Standard of Care: CNI and MPA: Tacrolimus or cyclosporine: dosed according to trough levels per standard of care Mycophenolate mofetil 750mg po bid or mycophenolate sodium 540mg po bid x 36 months
Measure Participants	0	0

5. Secondary Outcome

Title	Trans-vivo Delayed Type Hypersensitivity (DTH) Assay
Description	Delayed type hypersensitivity (DTH) reactivity status to donor and minor antigens will be detected using trans-vivo DTH assay. This information will help determine if T-regulatory cells are present, and whether such cells predict outcome of Calcineurin inhibitor withdrawal.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

The study was closed prematurely. Data were not collected

Arm/Group Title	MPA Monotherapy	Control: MPA and CNI
Arm/Group Description	Subjects will discontinue calcineurin inhibitor (cyclosporine or tacrolimus) and remain on MPA (mycophenolate mofetil or mycophenolate sodium) monotherapy Mycophenolic Acid: Mycophenolate mofetil: 750mg po bid x 36 months OR mycophenolate sodium 540mg po bid x 36 months	Subjects will continue with their current immunosuppressive regimen of MPA (mycophenolate mofetil or mycophenolate sodium) and calcineurin inhibitor (cyclosporine or tacrolimus) Standard of Care: CNI and MPA: Tacrolimus or cyclosporine: dosed according to trough levels per standard of care Mycophenolate mofetil 750mg po bid or mycophenolate sodium 540mg po bid x 36 months
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	Adverse events were not monitored.
Arm/Group Title	MPA Monotherapy		Control: MPA and CNI
Arm/Group Description	Subjects will discontinue calcineurin inhibitor (cyclosporine or tacrolimus) and remain on MPA (mycophenolate mofetil or mycophenolate sodium) monotherapy Mycophenolic Acid: Mycophenolate mofetil: 750mg po bid x 36 months OR mycophenolate sodium 540mg po bid x 36 months		Subjects will continue with their current immunosuppressive regimen of MPA (mycophenolate mofetil or mycophenolate sodium) and calcineurin inhibitor (cyclosporine or tacrolimus) Standard of Care: CNI and MPA: Tacrolimus or cyclosporine: dosed according to trough levels per standard of care Mycophenolate mofetil 750mg po bid or mycophenolate sodium 540mg po bid x 36 months
All Cause Mortality
	MPA Monotherapy		Control: MPA and CNI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	MPA Monotherapy		Control: MPA and CNI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	MPA Monotherapy		Control: MPA and CNI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.