Novel Desensitization Kidney Transplantation

Novel Desensitization Protocol With Proteasome Inhibitor and Costimulation Blockade for Highly Sensitized Patients to Allow for Successful Kidney Transplantation. A Pilot Study.

This proposal's objective is to determine whether belatacept, in conjunction with a proteasome inhibitor can be used to safely increase the likelihood of finding an acceptable donor for highly HLA sensitized kidney transplant candidates.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation; End Stage Kidney Disease (ESRD)
• Intervention / Treatment: Drug: Belatacept Injection

Detailed Description

This is a pilot study to test the safety and effectiveness of the desensitization therapy with belatacept and proteasome inhibitor to increase the likelihood of of finding an acceptable donor for highly HLA sensitized kidney transplant candidates.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Highly sensitized patient cPRA 99-100% AND actively listed for kidney transplantation at the kidney transplantation Program at University fo Chicago
• Ebstein Barr Virus (EBV) Immunoglobulins (IgG) seropositive
• No active systemic infection
• No allergy to proteasome inhibitors (Bortezomib), or to belatacept
• No known malignancy in the previous 2 years except for non-melanomatous skin cancer
• Female who agrees to practice 2 effective methods of contraception through 3 months after the last dose of Bortezomib
• Patient vaccinated against hepatitis B virus with positive level of HBsAb
• Patients fully vaccinated against Coronavirus Disease 2019 at least 2 weeks prior to the start of the 1st cycle.
• Actively listed for kidney transplant at the Transplant Institute at University of Chicago

Exclusion Criteria:

• Patient with significant neuropathy by the Common Terminology Criteria for Adverse Events (CTCAE) criteria within 14 days before enrollment (Grades 3-4 or Grade 2 with pain)
• Myocardial infarction within 6 months of enrollment or has Heart Failure in acute dialysis quality initiative (ADQI) ESRD classification system Class 2 non restrictive (2NR) or greater, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia or active conduction system abnormalities
• Patient who received other investigational drugs within 14 days prior to initiation of study treatment
• Receipt of a live vaccine within 4 weeks prior to initiation of study treatment
• Evidence of severe liver disease by history or physical exam or with abnormal liver profile ( > 1.5 times upper limit of normal within 30 days of consent)
• Female who is breast feeding or pregnant
• Untreated latent tuberculosis
• History of Post Transplant Lymphoproliferative Disease (PTLD)
• Patient still carrying previous kidney transplant.

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: Patients treated with belatacept and proteasome inhibitor; Highly sensitized patients will be treated with belatacept and proteasome inhibitor and monitored for decreasing calculated Panel of Reactive Antibodies (cPRA) and suitable kidney donor base don negative crossmatch	Drug: Belatacept Injection; Patient will initiate belatacept therapy and will received 2 cycles of proteasome inhibitor therapy; Other Names: proteasome inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Likelihood of finding a donor to whom the study participant does not have strong anti-donor HLA specific antibodies (DSA).	The likelihood of finding a suitable donor will calculated base on calculated Panel of Reactive Antibodies measured 1month after the therapy	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Strong Human Leukocyte Antigen (HLA) antibodies with mean fluorescence intensity (MFI) reduced by more than 50%	A number of strong HLA antibodies with MFI reduced by more than 50% will be counted	1 year
Time to transplant	Time from the beginning of the implementation of the therapy to kidney transplantation will be measured	1 year
Episodes of Antibody Mediated Rejection (AMR) and Acute Cellular Rejection (ACR)	Number of episodes of AMR and ACR after kidney transplantation will be counted	1 year
Death	The incidence of episodes of patient death will be calculated	1 year
Serious infection requiring inpatient intravenous therapies	Incidence rate of the episodes of serious infection requiring inpatient intravenous therapies will be calculated during the study	1 year
Post-transplant lymphoproliferative disorder	The incidence rate of the episodes of post-transplant lymphoproliferative disorder will be calculated	1 year

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Piotr Witkowski, MD PhD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Actual): September 12, 2025
• Study Completion (Actual): September 12, 2025

Study Registration Dates

• First Submitted: December 3, 2021
• First Submitted That Met QC Criteria: April 18, 2022
• First Posted (Actual): April 26, 2022

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: kidney transplantation; proteasome inhibitor; sensitized patients; belatacept
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Pathological Conditions, Signs and Symptoms; Kidney Failure, Chronic; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Immunoconjugates; Amino Acids, Peptides, and Proteins; Proteins; Pharmacologic Actions; Chemical Actions and Uses; Antibodies; Immunoglobulins; Blood Proteins; Serum Globulins; Globulins; Abatacept; Proteasome Inhibitors
• Other Study ID Numbers: IRB21-0323

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No