Clinical trial NCT02078193: Efficacy of Belatacept in Reducing DSA
Official title: An Exploratory, Open-label, Single Center Study to Assess the Efficacy of NULOJIX (Belatacept) in Reducing Donor Specific Human Leukocyte Antigen (HLA) Antibody (DSA) Strength in Maintenance Kidney Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Transplantation
Lead sponsor: East Carolina University
Sponsor class: OTHER
First posted: 2014-03-05
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to demonstrate that administration of belatacept in maintenance kidney transplant recipients may cause a reduction in Donor Specific HLA Antibody (DSA).

Detailed description: The aim of this study is to evaluate patients converted to belatacept in combination with Mycophenolate Mofetil (MMF) with corticosteroids with respect to their DSA titer. Patients in this study will be converted from their calcineurin inhibitor (CNI) to belatacept from baseline in an attempt to down-modulate antibody production by B-cells. Dosing will be calculated per prescribing information for dosing maintenance phase (5mg per kg every 28 days.

Eligibility criteria: Inclusion Criteria:

* Recipients of cadaveric, living related or living unrelated kidney transplant with positive DSA titer (two positive tests) and enrolled within 6 months of DSA detection.
* Patients with stable renal function. Stable renal function is defined as one serum creatinine (SCr) value that is +/- 10% of the baseline SCr within 3 months of enrollment (eGFR \>/= 35 and \</= 75 mL/min/1.73m\^2).
* Patients who are EBV seropositive
* Males and females, 18-75 years of age;
* Patients currently receiving mycophenolic acid (MPA) (CellCept daily or myfortic daily), cyclosporine or tacrolimus with corticosteroids as part of their immunosuppressive regimen
* Patients willing to be converted to belatacept from cyclosporine or tacrolimus.
* 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 HLA identical
* Patients who are Epstein-Barr virus (EBV) seronegative
* 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. Aspartate Aminotransferase (AST), Alanine Aminotransferase (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 belatacept;
* 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 human chorionic gonadotropin (hCG) laboratory test (local); females of childbearing potential who are unwilling to use effective study-approved contraceptives and who are planning to become pregnant; Sexually active fertile men must use effective birth control if their partners are women of child bearing potential;
* 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.

Primary outcomes:
measure: Change of Donor Specific Antibodies (DSA)
timeFrame: one year
Secondary outcomes:
measure: Safety
timeFrame: one year
Other outcomes:
measure: Number of Participants With Chronic Kidney Rejection
timeFrame: One year
Locations:
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
Study officials:
affiliation: East Carolina University, Department Chair of Internal Medicine
name: Paul Bolin, MD
role: PRINCIPAL_INVESTIGATOR
References: