Efficacy of Belatacept in Reducing DSA

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

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).

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Belatacept

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • East Carolina University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Belatacept; Participants will be converted from their current MMF to once a month infusions of Belatacept	Drug: Belatacept; Patients will be converted from their MMF to Belatacept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Donor Specific Antibodies (DSA)	DSA levels will be measured using microbeads coated with Class I or Class II human leukocyte antigens (HLA) and read using a Luminex flow cytometer. Participants will be converted from their current Mycophenolate Mofetil (MMF) to once a month infusions of Belatacept.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Incidence of infections	one year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Chronic Kidney Rejection	Incidence of chronic kidney rejection	One year

Collaborators and Investigators

• Sponsor: East Carolina University
• Investigators: Principal Investigator: Paul Bolin, MD, East Carolina University, Department Chair of Internal Medicine

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: March 3, 2014
• First Submitted That Met QC Criteria: March 4, 2014
• First Posted (Estimate): March 5, 2014

Study Record Updates

• Last Update Posted (Actual): August 1, 2017
• Last Update Submitted That Met QC Criteria: July 6, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: IM103-302