Cellular Immunotherapy for Immune Tolerance in Past Recipients of HLA Zero-mismatch, Living Donor Kidney Transplants

A Phase 2 Prospective, Multi-center, Open-label Trial to Assess the Safety & Efficacy of Cellular Immunotherapy With MDR-103 for Induction of Mixed Chimerism & Immune Tolerance in Past Recipients of HLA Zero-mismatch, LD Kidney Transplants

The primary objective of this study is to demonstrate the safety and efficacy of cellular immunotherapy with MDR-103 for induction of functional immune tolerance in past recipients of human leukocyte antigen (HLA)-matched, living donor kidney transplants.

Study Overview

• Status: Withdrawn
• Conditions: Kidney Transplant Rejection
• Intervention / Treatment: Biological: MDR-103

Detailed Description

Currently, patients receiving a transplanted kidney are required to take life-long immunosuppressive medications to prevent rejection of the transplanted kidney. These medications carry substantial side effects. In addition, these medicines often do not completely control damage to the kidney from the recipients' immune system, ultimately causing the kidney to fail.

Medeor Therapeutics is developing a novel cell-based therapy to reprogram the past recipients' immune system to accept the transplanted kidney without the concurrent need for long term use of immunosuppressive drugs.

The purpose of the current Phase 2 study is to demonstrate the efficacy and safety of MDR-103 for the induction of transplant immune tolerance in a prospective, multicenter clinical trial. MDR-103 is intended to induce mixed lymphohematopoietic chimerism and donor specific immune tolerance in order to preserve transplant kidney function, avert transplant kidney rejection, and eliminate the cumulative and serious side effects associated with immunosuppressive drugs.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Recipient Inclusion Criteria:

• Past recipient of a first kidney allograft from an HLA-matched, living related donor
• Age ≥18 and ≤70 years
• Single solid organ recipient (kidney only)
• ABO compatibility with donor

Donor Inclusion Criteria:

• HLA-matched first degree (parent, child or sibling) or second-degree (child of a sibling, half sibling) relative of the prospective recipient participant
• Age ≥18 and ≤70 years
• Past living related kidney donor, and capable of undergoing G-CSF mobilization and apheresis of hematopoietic cells

Exclusion Criteria:

Recipient Exclusion Criteria:

• Underlying kidney disease with a high risk of disease recurrence in the transplanted kidney
• Baseline positive donor-specific anti-HLA antibody testing
• Is taking immunosuppressive therapy
• Evidence of prior hepatitis B (HBV) or hepatitis C (HCV)

Donor Exclusion Criteria:

• History of autoimmune disorders
• History of type 1 or type 2 diabetes mellitus
• Tests confirmed positive for human immunodeficiency virus (HIV), HBV, HCV
• History of infection with Zika virus

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: Investigational Arm; A low-dose Total Lymphoid Irradiation (TLI) and anti-thymocyte globulin (ATG) combined with a single IV infusion of MDR-103 and standard anti-rejection medications in past recipients of HLA Zero-mismatch living donor kidney transplants.	Biological: MDR-103; MDR-103 Enriched CD34+ hematopoietic stem cells and defined dose of CD3+ T-cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistent Mixed Chimerism	The primary efficacy endpoint is the proportion of subjects achieving persistent mixed chimerism in MDR-103 treated recipients of past HLA zero-mismatch living donor kidney transplants. Persistent Mixed Chimerism - is defined as at least 6 months of persistent WBC mixed chimerism consisting of at least 5% donor cells in whole blood or in at least one WBC lineage (CD3+ T cells, CD33+ myeloid cells, CD19+ B cells, and/or CD56+ NK cells).	At 6 months post initiation of anti-thymocyte globulin (ATG) conditioning therapy

Collaborators and Investigators

• Sponsor: Medeor Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: July 20, 2018
• First Submitted That Met QC Criteria: July 27, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Actual): June 7, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Immunosuppression; Immunotherapy; Kidney Failure; Kidney Transplant; T cells; CD34+; Cellular Therapy; Living Donor; HLA-matched; CD3+; Anti-rejection therapy; Hematopoietic Stem Cells (HSC)
• Other Study ID Numbers: MDR-103-L2K

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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