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

Transplant; Failure, Kidney Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01044303
• Other study ID #: CERL080A-US78T
• Status: Completed
• Phase: Phase 4
• First received: January 6, 2010
• Last updated: October 16, 2014
• Start date: January 2010
• Est. completion date: April 2013

Study information

• Verified date: October 2014
• Source: East Carolina University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Insufficiency
• Transplant; Failure, Kidney

Intervention

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.

Locations

Country	Name	City	State
United States	East Carolina University	Greenville	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
East Carolina University	Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change in Mean Fluorescence Index (MFI) of Donor Specific Antibodies (DSA) With Increasing Doses of Enteric-Coated Mycophenolate Sodium (EC-MPS)		24 months	No
Secondary	To Assess the Rate of Rejection, Infection and Renal Function as Mycophenolic Acid Dose is Increased.		24 months	Yes