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

Kidney Transplant Rejection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03363945
• Other study ID #: MDR-101-MLK
• Status: Completed
• Phase: Phase 3
• Start date: March 15, 2018
• Est. completion date: April 11, 2024

Study information

• Verified date: June 2024
• Source: Medeor Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: April 11, 2024
• Est. primary completion date: April 11, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Kidney Transplant Rejection

Intervention

Biological:
• MDR-101
Enriched CD34+ hematopoietic stem cells and defined dose of CD3+ T-cells

Locations

Country	Name	City	State
Canada	CIUSSS de l'Est- de-l'Île-de-Montréal Installation Hopital Maisonneuve-Rosemont	Montréal	Quebec
United States	University of Colorado Denver	Aurora	Colorado
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	INOVA Fairfax Hospital	Fairfax	Virginia
United States	The Methodist Hospital	Houston	Texas
United States	Mayo Clinic Hospital	Jacksonville	Florida
United States	Loma Linda University Medical Center	Loma Linda	California
United States	USC	Los Angeles	California
United States	University of Wisconsin School of Medicine	Madison	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
United States	Intermountain Transplant Center	Murray	Utah
United States	Yale University	New Haven	Connecticut
United States	RWJBarnabas Health	Orange	New Jersey
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Stanford University Medical Center	Stanford	California
United States	Upstate University Hospital	Syracuse	New York
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Medeor Therapeutics, Inc.	California Institute for Regenerative Medicine (CIRM)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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