Clinical trial NCT02130817: Belatacept in Kidney Transplantation of Moderately Sensitized Patients
Official title: Belatacept for the Management of Moderately Sensitized Patients at Risk for Delayed Graft Function (DGF)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: End Stage Renal Disease
Antibody Mediated Rejection
Keywords: Renal Transplant
Kidney Transplant
Mean flourescent Intensity
Delayed Graft Function
Antagonist of Thymocyte Cell Activation
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2014-05-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and effectiveness of an immunosuppressive medication, Belatacept, as a replacement for a calcineurin inhibitor, in combination with a standard of care regimen of immunosuppressive medications and plasma exchange (plasmapheresis and immunoglobulin treatment) for kidney transplant patients who are moderately sensitized against their deceased donor and at-risk for delayed graft function. The hypothesis is that moderately sensitized patients who receive Belatacept treatment with the standard of care regimen will lead to lower acute rejection rates than historical controls based on assessment of standard of care biopsies and standard Banff criteria.

Detailed description: This exploratory single-center, open-label safety and efficacy study will enroll 20 adult kidney transplants candidates, moderately sensitized against their deceased donor and at-risk for delayed graft function (DGF), to receive Belatacept (days 0,5, weeks 2,4,8 and 12 (10 mg/kg), and every 4 weeks thereafter (5 mg/kg)), plasma exchange (once before and twice after transplant) and Intravenous Immunoglobulin (IVIG) (100 mg/kg after each plasma exchange), along with Thymoglobulin (ATG) induction and Dexamethasone tapered dosing starting on the day of transplant at 100mg IV, tapered through Day 4, followed by prednisone at 30 mg on Day 5 with tapered dosing to prednisone 10 mg/d by one month, with a total observation period of 1 year. Patients will be tapered off tacrolimus by week 8 and will remain on mycophenolic acid and prednisone for the total length of the study. Subjects will be followed until 1 year post transplant.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects 18-70 years of age
* Patient who is receiving an expanded criteria donor (ECD) or deceased cardiac donor (DCD) kidney
* Have immunodominant donor specific antibodies (DSA) 1,000 - 4,000 mean fluorescent intensity (MFI) by single bead Luminex bioassay
* Subjects must be capable of understanding the investigational nature and risks of the study and must sign a statement of informed consent
* Female patients of child bearing potential must have a negative urine or serum pregnancy test within the past 48 hours prior to study inclusion and be willing to use contraceptives for the duration of the study and for 8 weeks after the last dose of study drug Women of Child-Bearing Potential (WOCBP) includes
* Women who have experienced menarche and who have not undergone successful surgical sterilization or who are not post-menopausal
* Women using oral contraceptives, other hormonal contraceptives, or mechanical products such as intrauterine devices or barrier methods
* Women who are practicing abstinence
* Women who have a partner who is sterile (eg, due to vasectomy).
* Women must not be breast-feeding
* Male subjects must agree to use an acceptable method for contraception for the duration of the study
* Patient must have known positive Epstein-Barr virus (EBV) serostatus

Exclusion Criteria:

* Patient has previously received an organ transplant other than a kidney.
* Patient is receiving an human leukocyte antigen (HLA) identical living donor transplant
* Patient who is a recipient of a multiple organ transplant
* Patient with a positive T or B cell crossmatch
* Patient with a donor specific antibody (DSA) as deemed by the local PI to be associated with significant risk of rejection
* Patient has received an ABO incompatible donor kidney
* Recipients will be receiving a dual or en bloc kidney transplant
* Donor anticipated cold ischemia is \> 30hours
* Recipient or donor is known to be seropositive for hepatitis C virus (HCV) or B virus (HBV) except for hepatitis B surface antibody positive. HCV seropositive patients with a negative HCV viral load testing may be included.
* Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV)
* Seronegative or unknown EBV serostatus
* Patient has uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives
* Patients with tuberculosis who have not been treated for latent infection.
* Patients at high risk for polyoma virus-associated nephropathy, which is mostly due to BK virus infection
* Patients at high risk for polyoma virus-associated nephropathy, which is mostly due to BK virus infection
* Patients with thrombocytopenia (PLT \<75,000/mm3), and/or leucopoenia (WBC \< 2,000/mm3), or anemia (hemoglobin \< 6 g/dL) prior to study inclusion.
* Patient is taking or has been taking an investigational drug in the 30 days prior to transplant
* Patient who has undergone desensitization therapy within 6 months prior to transplant
* Patient has a known hypersensitivity to belatacept, tacrolimus, mycophenolate mofetil, alemtuzumab, rabbit anti-thymocyte globulin, or glucocorticoids
* Patient is receiving chronic steroid therapy at the time of transplant
* Patients with a history of cancer (other than non-melanoma skin cell cancers cured by local resection) within the last 5 years
* Patients with \> Grade 2 peripheral neuropathy within 14 days before enrollment
* Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiography evidence of acute ischemia or active conduction system abnormalities.
* Female subject is pregnant or breast-feeding
* Serious medical or psychiatric illness likely to interfere with participation in this clinical study. Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness
* Prisoners or subjects who are involuntarily incarcerated

Primary outcomes:
measure: Acute rejection
timeFrame: one year
Secondary outcomes:
measure: Patient and Graft Survival
timeFrame: One year
measure: Incidence of infections
timeFrame: One year
measure: Incidence of de novo donor specific antibody (DSA)
timeFrame: One year
measure: Incidence of new onset diabetes
timeFrame: One year
measure: Increase in estimated Glomerular Filtration Rate (eGFR)
timeFrame: One year
measure: Incidence of malignancies
timeFrame: One year
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wiscsonsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Arjang Djamali, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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