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

NCT03605654 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: MDR-102-mMLK
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Kidney Transplant Rejection

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (3)

Investigational Arm

EXPERIMENTAL

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

Active Control Arm

ACTIVE COMPARATOR

Standard anti-rejection medications that would be given to kidney transplant recipients who are outside the study

Drug: Immunosuppressive Agents

Non-Randomized Exploratory Arm

EXPERIMENTAL

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

Interventions

MDR-102 BIOLOGICAL

Enriched CD34+ hematopoietic stem cells and defined dose of CD3+ T-cells

Investigational Arm; Non-Randomized Exploratory Arm

Immunosuppressive Agents DRUG

Standard Anti-Rejection Medications that would be given to kidney transplant recipients who are outside the study

Also known as: Corticosteroids, Mycophenolate Mofetil, Tacrolimus

Active Control Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Medeor Therapeutics, Inc.: lead

MeSH Terms

Interventions

Immunosuppressive Agents; Adrenal Cortex Hormones; Mycophenolic Acid; Tacrolimus

Intervention Hierarchy (Ancestors)

Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones

Study Officials

• Lenuta Micsa, MD

  Medeor Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A low-dose Total Lymphoid Irradiation and anti- thymocyte globulin combined with a single infusion of MDR-102

Study Record Dates

• First Submitted: July 20, 2018
• First Posted: July 30, 2018
• Study Start: December 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: June 7, 2024

Record last verified: 2024-06