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

NCT03363945 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: MDR-101-MLK
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 19

Brief Summary

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.

Conditions

Kidney Transplant Rejection

Keywords

kidney transplant; cellular therapy; anti-rejection therapy; living donor; HLA-matched; hematopoietic stem cells (HSC); CD34+; CD3+; T cells

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

MDR-101

ACTIVE COMPARATOR

A single dose will be administered via IV infusion post-kidney transplant.

Biological: MDR-101

Control Arm

NO INTERVENTION

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.

Interventions

MDR-101 BIOLOGICAL

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

MDR-101

Eligibility Criteria

• Age: 18 Years - 70 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 HLA-matched, living related donor
• Age ≥18 and ≤70 years
• Single solid organ recipient (kidney only)
• ABO matched with donor

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
• Evidence of prior hepatitis B (HBV) or hepatitis C (HCV)
• 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
• 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

Sponsors & Collaborators

• Medeor Therapeutics, Inc.: lead
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (19)

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

USC

Los Angeles, California, 90033, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Yale University

New Haven, Connecticut, 06519, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Mayo Clinic Hospital

Jacksonville, Florida, 32224, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153-3328, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

RWJBarnabas Health

Orange, New Jersey, 07052, United States

Location

Upstate University Hospital

Syracuse, New York, 13210, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

Intermountain Transplant Center

Murray, Utah, 84107, United States

Location

INOVA Fairfax Hospital

Fairfax, Virginia, 22031, United States

Location

University of Wisconsin School of Medicine

Madison, Wisconsin, 53792, United States

Location

CIUSSS de l'Est- de-l'Île-de-Montréal Installation Hopital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Study Officials

• Lenuta Micsa, MD

  Medeor Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Total lymphoid irradiation and anti-thymocyte globulin

Study Record Dates

• First Submitted: November 30, 2017
• First Posted: December 6, 2017
• Study Start: March 15, 2018
• Primary Completion: April 11, 2024
• Study Completion: April 11, 2024
• Last Updated: June 7, 2024

Record last verified: 2024-06

Locations

US (18); CA (1)