Cellular Immunotherapy in Recipients of Human Leukocyte Antigen (HLA)-Mismatched, Living Donor Kidney Transplants

Study Overview
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Brief Summary
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The Phase 2 primary objective is to evaluate achievement of persistent mixed chimerism and withdrawal of at least one immunosuppression drug for a minimum of 6 months with no episodes of biopsy-proven acute rejection or transplant kidney loss induced by cellular immunotherapy with MDR-102 in recipients of 1, 2, or 3 out of 6 human leukocyte antigen (HLA)-mismatched, living donor kidney transplants. The Phase 3 primary objective is to evaluate achievement of induction of immune quiescence by cellular immunotherapy with MDR-102 in recipients of 1, 2, or 3 out of 6 HLA-mismatched, living donor kidney transplants. Immune quiescence is defined as remaining on maintenance immunosuppression monotherapy with Tac or CsA for 12 months or more after completion of anti-rejection immunosuppression drug therapy reduction with no episodes of biopsy-proven acute rejection, transplant kidney loss, or subject deat.

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 as personalized cellular immunotherapies to improve outcomes in organ transplant recipients. The purpose of the current Phase 2/3 study is to demonstrate the efficacy and safety of MDR-102 for the induction of immune quiescence in a prospective, randomized, open-label, multi-center clinical trial. MDR-102 is intended to induce mixed lymphohematopoietic chimerism and donor specific immune quiescence in order to preserve transplant kidney function, avert transplant kidney rejection, and reduce the cumulative and serious side effects associated with immunosuppression drugs.

Official Title
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A Phase 2/3, Prospective, Randomized, Multi-center, Open-Label, Controlled Trial to Assess the Efficacy & Safety of Cellular Immunotherapy With MDR-102 for Induction of Immune Quiescence™in Recipients of HLA-mismatched, LD Kidney Transplants

Conditions
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Kidney Transplant Rejection

Intervention / Treatment
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* Biological: MDR-102
* Drug: Immunosuppressive Agents


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipient Inclusion Criteria: Planned recipient of a first kidney allograft from an human leukocyte antigen (HLA)-matched, living related donor. Zero-mismatch transplants are excluded Age ≥18 and ≤65 years Single solid organ recipient (kidney only) ABO compatibility with donor Donor Inclusion Criteria: Human leukocyte antigen (HLA)-mismatched first degree (parent, child or sibling) or second-degree (child of a sibling) relative of the prospective recipient participant. Zero-mismatch transplants are excluded Age ≥18 and ≤65 years Prepared to be a living related kidney donor, and capable of undergoing granulocyte-colony stimulating factor (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 Prior hematopoietic cell transplant, organ transplant, any cell therapy, or any gene 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: A low-dose Total Lymphoid Irradiation and anti- thymocyte globulin combined with a single infusion of MDR-102
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational Arm<br>A low-dose Total Lymphoid Irradiation and anti- thymocyte globulin combined with a single infusion of MDR-102 post-kidney transplant and standard anti-rejection medications in recipients of 1, 2, or 3 out of 6 human leukocyte antigen (HLA)-mismatched, living donor kidney transplants | Biological: MDR-102<br>* Enriched CD34+ hematopoietic stem cells and defined dose of CD3+ T-cells<br>|
| Active Comparator: Active Control Arm<br>Standard anti-rejection medications that would be given to kidney transplant recipients who are outside the study | Drug: Immunosuppressive Agents<br>* Standard Anti-Rejection Medications that would be given to kidney transplant recipients who are outside the study<br>* Other names: Tacrolimus;|
| Experimental: Non-Randomized Exploratory Arm<br>A low-dose Total Lymphoid Irradiation and anti- thymocyte globulin combined with a single infusion of MDR-102 post-kidney transplant and standard anti-rejection medications in recipients of 4, 5, or 6 out of 6 human leukocyte antigen (HLA)-mismatched, living donor kidney transplants | Biological: MDR-102<br>* Enriched CD34+ hematopoietic stem cells and defined dose of CD3+ T-cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2 Primary Outcome: Achievement of persistent mixed chimerism and withdrawal of at least one Immunosuppression drug for a minimum of 6 months | Persistent mixed chimerism is defined as: • At least 6 months of persistent white blood cells mixed chimerism consisting of at least 5% donor white blood cells in whole blood or in at least one white blood cells lineage | 6 months | 
| Phase 3 Primary Outcome: proportion of subjects achieving immune quiescence | Immune quiescence is defined as: Achievement of the required duration of persistent donor mixed chimerism (i.e., 6 months) to permit mycophenolic acid drug (e.g., mycophenolate mofetil) immunosuppression stoppage without a taper at approximately 12 months post-kidney transplant surgery, Successful stoppage of mycophenolic acid drug (e.g., mycophenolate mofetil) at 12 + 1 months post-kidney transplant surgery, and Subsequent successful maintenance on calcineurin inhibitor monotherapy for at least 12 additional months (out to at least 24 months post-kidney transplant surgery) without biopsy-proven acute rejection, transplant kidney loss, or subject death | 24 months |