Reducing Donor Specific Antibody (DSA) Strength in Maintenance Kidney Transplant Recipients (DSA Study)

• Sponsor: East Carolina University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01044303
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 32
• Location: 1
• Arm: 1
• Duration (Months): 39
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate that increased dosages of mycophenolic acid in maintenance kidney transplant recipients may cause a reduction in donor-specific antibodies.

Condition or Disease	Intervention/Treatment	Phase
Transplant; Failure, Kidney	Drug: Myfortic Escalation	Phase 4

Detailed Description

The development of DSA post-transplant has been associated with chronic rejection and graft failure. EC-MPS is thought to be the key drug preventing both cellular and antibody mediated rejections. Several studies have shown that recipients receiving an optimal dose of EC-MPS have fewer antibody mediated rejections and may require a lower dose of calcineurin inhibitors and/or corticosteroids thus reducing side effects and extending graft survival.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Exploratory, Open-Label, Single Center Study to Assess the Efficacy and Dose Titration of Enteric-Coated Mycophenolate Sodium (EC-MPS) in Reducing Donor Specific Antibody (DSA) Strength in Maintenance Kidney Transplant Recipients
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Myfortic Escalation Participants EC-MPS dose was escalated to a minimum daily dose of 1440mg or equivalent, with the maximum dose never exceeding the manufacturer's recommendations.	Drug: Myfortic Escalation; Dose increases of 180 mg every 3 months until DSA titer is zero or until maximum tolerable dose of EC-MPS is achieved. Maximum dose will not exceed 2160 mg daily.; Other Names: Enteric-coated mycophenolate sodium

Outcome Measures

Primary Outcome Measures

1. Percent Change in Mean Fluorescence Index (MFI) of Donor Specific Antibodies (DSA) With Increasing Doses of Enteric-Coated Mycophenolate Sodium (EC-MPS) [24 months]

Secondary Outcome Measures

1. To Assess the Rate of Rejection, Infection and Renal Function as Mycophenolic Acid Dose is Increased. [24 months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Recipients of cadaveric, living related or living unrelated kidney transplant with positive DSA titer.

• Males and females, 18-75 years of age.

• Patients currently receiving MPA (500mg to 2500 mg of CellCept daily or 360 mg to 1800 mg of myfortic daily), cyclosporine or tacrolimus with or without corticosteroids as part of their immunosuppressive regimen for at least 6 months.

• Females of childbearing potential must have a negative pregnancy test prior to enrollment. The test should be performed at baseline visit. Effective contraception must be used during the trial, and for 4 weeks following discontinuation of the study medication.

• Patients who are willing and able to participate in the full course of the study and from whom written informed consent has been obtained.

Exclusion criteria:

• Multi-solid or cellular organ transplants (e.g. combined with pancreas, liver, islet, bone marrow), either concurrent or previous (with exception that a second kidney transplant is allowed).

• Evidence of graft rejection or treatment of acute rejection within 14 days prior to Baseline visit.

• Patients who have received any investigational drug within 4 weeks prior to study entry.

• Patients with thrombocytopenia (<75,000/mm3), with an absolute neutrophil count of <1,500/mm3 and/or leukocytopenia (<4,000/mm3), and/or hemoglobin <9.0 g/dL prior to enrollment.

• The presence of a severe GI disorder (such as Irritable Bowel Syndrome, Inflammatory Bowel Disease and known Peptic Ulcer Disease).

• Presence of clinically significant infection requiring continued therapy, chronic infection (e.g. HIV, Hep B and Hep C), malignancy (within last 5 years, except excised squamous or basal cell carcinoma of the skin), lymphoma or renal toxicity that would interfere with the appropriate conduct of the study.

• Evidence of severe liver disease (incl. abnormal liver profile i.e. AST, ALT or total bilirubin ≥ 3 times ULN) or severe diarrhea or active peptic ulcer disease that would interfere with the appropriate conduct of the study.

• Abnormal physical or laboratory findings of clinical significance within 2 weeks of inclusion which would interfere with the objectives of the study.

• Patients with symptoms of significant somatic or mental illness or evidence of drug and/or alcohol abuse.

• Patients receiving > 10 mg/day prednisone dose.

• History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures to MPA.

• Patients not making DSA antibodies.

• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (local); females of childbearing potential who are unwilling to use effective means of contraception and who are planning to become pregnant.

• Any other medical condition that, in the opinion of the site investigator based on recall or chart review would interfere with completing the study, including but not limited to visual problems or cognitive impairment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	East Carolina University	Greenville	North Carolina	United States	27834

Sponsors and Collaborators

• East Carolina University
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Paul Bolin, MD, East Carolina University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Paul Bolin, Chair of Internal Medicine, East Carolina University
• ClinicalTrials.gov Identifier: NCT01044303
• Other Study ID Numbers: CERL080A-US78T
• First Posted: Jan 7, 2010
• Last Update Posted: Oct 20, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by Paul Bolin, Chair of Internal Medicine, East Carolina University: Kidney Transplantation; Mycophenolic Acid; Donor-Specific Antibodies; Kidney Rejection
• Additional relevant MeSH terms: Renal Insufficiency; Mycophenolic Acid

Study Results

Participant Flow

Arm/Group Title	Mycophenolic Acid Escalation
Arm/Group Description	Participants MPA dose was escalated to a minimum daily dose of 1440mg or equivalent, with the maximum dose never exceeding the manufacturer's recommendations. Enteric-coated mycophenolate sodium: Dose increases of 180 mg every 3 months until DSA titer is zero or until maximum tolerable dose of mycophenolic acid is achieved. Maximum dose will not exceed 2160 mg daily.
Period Title: Overall Study
STARTED	32
COMPLETED	30
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Mycophenolic Acid Escalation
Arm/Group Description	Participants MPA dose was escalated to a minimum daily dose of 1440mg or equivalent, with the maximum dose never exceeding the manufacturer's recommendations. Enteric-coated mycophenolate sodium: Dose increases of 180 mg every 3 months until DSA titer is zero or until maximum tolerable dose of mycophenolic acid is achieved. Maximum dose will not exceed 2160 mg daily.
Overall Participants	32
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	28 87.5%
>=65 years	4 12.5%
Sex: Female, Male (Count of Participants)
Female	12 37.5%
Male	20 62.5%
Region of Enrollment (participants) [Number]
United States	32 100%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Mean Fluorescence Index (MFI) of Donor Specific Antibodies (DSA) With Increasing Doses of Enteric-Coated Mycophenolate Sodium (EC-MPS)
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

This was a pilot study to examine the effect of MPA escalation on DSA reduction.

Arm/Group Title	Mycophenolic Acid (MPA) Escalation
Arm/Group Description	Patients receiving MPA (500mg to 2500mg of CellCept daily or 360mg to 1800mg myfortic daily), cyclosporine or tacrolimus with or without corticosteroids as part of their immunosuppressive regimen for at least 6 months
Measure Participants	30
Mean (Standard Deviation) [percent of MFI change]	43.1 (31.45)

2. Secondary Outcome

Title	To Assess the Rate of Rejection, Infection and Renal Function as Mycophenolic Acid Dose is Increased.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rate of Infection	Rate of Rejection	Renal Function
Arm/Group Description	Number of patients who had an infection during the course of the study.	Number of patients who had a rejection during the course of the study.	Number of patients who had stable renal function throughout the study.
Measure Participants	30	30	30
Number [participants]	2 6.3%	2 NaN	29 NaN

Adverse Events

Arm/Group Title	Adverse Events
Arm/Group Description	Adverse events reported by participants during the course of the study.
All Cause Mortality
	Adverse Events
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Adverse Events
	Affected / at Risk (%)	# Events
Total	5/30 (16.7%)
Blood and lymphatic system disorders
Sepsis	1/30 (3.3%)	1
Endocrine disorders
Pancreatitis	1/30 (3.3%)	1
Gastrointestinal disorders
Diarrhea	2/30 (6.7%)	2
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	Adverse Events
	Affected / at Risk (%)	# Events
Total	5/30 (16.7%)
Blood and lymphatic system disorders
CMV	1/30 (3.3%)	1
Gastrointestinal disorders
Diarrhea	3/30 (10%)	3
Nausea	1/30 (3.3%)	1

Limitations/Caveats

Lost to follow-up was a limitation in this study.

More Information

Certain Agreements

Principal Investigators are NOT 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.