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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Kidney Transplant Rejection
• Intervention / Treatment: Biological: MDR-101

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 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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H1T 2M4
      • CIUSSS de l'Est- de-l'Île-de-Montréal Installation Hopital Maisonneuve-Rosemont
• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Los Angeles, California, United States, 90033
      • USC
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Hospital
  • Illinois
    • Maywood, Illinois, United States, 60153-3328
      • Loyola University Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Jersey
    • Orange, New Jersey, United States, 07052
      • RWJBarnabas Health
  • New York
    • Syracuse, New York, United States, 13210
      • Upstate University Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • The Methodist Hospital
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Transplant Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Fairfax Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MDR-101; A single dose will be administered via IV infusion post-kidney transplant.	Biological: MDR-101; Enriched CD34+ hematopoietic stem cells and defined dose of CD3+ T-cells
No Intervention: Control Arm; 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?

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

Collaborators and Investigators

• Sponsor: Medeor Therapeutics, Inc.
• Collaborators: California Institute for Regenerative Medicine (CIRM)
• Investigators: Study Director: Lenuta Micsa, MD, Medeor Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2018
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: November 30, 2017
• First Submitted That Met QC Criteria: November 30, 2017
• First Posted (Actual): December 6, 2017

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

• Keywords: kidney transplant; cellular therapy; T cells; CD34+; living donor; anti-rejection therapy; HLA-matched; hematopoietic stem cells (HSC); CD3+
• Other Study ID Numbers: MDR-101-MLK

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
• product manufactured in and exported from the U.S.: No