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

Sponsor

Medeor Therapeutics, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT03606746

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant Rejection	Biological: MDR-103	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Aug 1, 2025

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Persistent Mixed Chimerism [At 6 months post initiation of anti-thymocyte globulin (ATG) conditioning therapy]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)