Cellular Immunotherapy in Recipients of HLA-matched, Living Donor Kidney Transplants

Study Overview
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Brief Summary
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The primary objective of this study is to demonstrate the safety and efficacy of cellular immunotherapy with MDR-101 for induction of functional immune tolerance in recipients of human leukocyte antigen (HLA)-matched, living donor kidney transplants.

Detailed Description
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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 recipients' immune system to accept a transplanted kidney without the need for long term use of immunosuppression drugs. The purpose of the current Phase 3 study is to demonstrate the efficacy and safety of MDR-101 for the induction of transplant immune tolerance in a prospective, randomized, multicenter clinical trial. MDR-101 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.

Official Title
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A Phase 3, Randomized, Multi-center, Open-label, Controlled Trial to Assess the Efficacy and Safety of Cellular Immunotherapy With MDR-101 for Induction of Immune Tolerance in Recipients of HLA-matched, Living Donor Kidney Transplants

Conditions
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Kidney Transplant Rejection

Intervention / Treatment
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* Biological: MDR-101


Participation Criteria
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Eligibility Criteria
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Recipient Inclusion Criteria: Planned 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 matched with donor 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 Inclusion Criteria: HLA-matched first degree (parent, child or sibling) or second-degree (child of a sibling or half sibling) relative of the prospective recipient participant Age ≥18 and ≤70 years Prepared to be a living related kidney donor, and capable of undergoing G-CSF mobilization and apheresis of hematopoietic cells 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, T. cruzi, or syphilis History of infection with Zika virus

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Total lymphoid irradiation and anti-thymocyte globulin
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MDR-101<br>A single dose will be administered via IV infusion post-kidney transplant. | Biological: MDR-101<br>* Enriched CD34+ hematopoietic stem cells and defined dose of CD3+ T-cells<br>|
| No Intervention: Control Arm<br>Subjects randomized to this arm will receive the standard anti-rejection medications that would be given to kidney transplant recipients who are outside the study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional immune tolerance defined as | Achievement of the required duration of persistent donor mixed chimerism to permit calcineurin inhibitor immunosuppressive withdrawal beginning at 6-7 months post-kidney transplant surgery, and Successful withdrawal from all immunosuppressives by at least 12 months post-kidney transplant surgery, and Subsequent successful maintenance off all immunosuppressive drugs for at least 24 additional months (out to at least 36 months post-kidney transplant surgery) without biopsy-proven acute rejection, de novo Donor Specific Antibody, transplant kidney loss, or subject death. Loss to follow-up will be adjudicated as a failure in intent-to-treat analysis. | Up to 36 months post-kidney transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney transplant, cellular therapy, anti-rejection therapy, living donor, HLA-matched, hematopoietic stem cells (HSC), CD34+, CD3+, T cells