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

October 17, 2023 updated by: Medeor Therapeutics, Inc.

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

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.

Study Overview

Status

Not yet recruiting

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 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.

Study Type

Interventional

Enrollment (Estimated)

172

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Investigational Arm
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
Enriched CD34+ hematopoietic stem cells and defined dose of CD3+ T-cells
Active Comparator: Active Control Arm
Standard anti-rejection medications that would be given to kidney transplant recipients who are outside the study
Standard Anti-Rejection Medications that would be given to kidney transplant recipients who are outside the study
Other Names:
  • Corticosteroids
  • Mycophenolate Mofetil
  • Tacrolimus
Experimental: Non-Randomized Exploratory Arm
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
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
Phase 2 Primary Outcome: Achievement of persistent mixed chimerism and withdrawal of at least one Immunosuppression drug for a minimum of 6 months
Time Frame: 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
Time Frame: 24 months

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Lenuta Micsa, MD, Medeor Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2024

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

October 1, 2026

Study Registration Dates

First Submitted

July 20, 2018

First Submitted That Met QC Criteria

July 26, 2018

First Posted (Actual)

July 30, 2018

Study Record Updates

Last Update Posted (Actual)

October 19, 2023

Last Update Submitted That Met QC Criteria

October 17, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Kidney Transplant Rejection

Clinical Trials on MDR-102

3
Subscribe