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

Sponsor

Medeor Therapeutics, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03363945

Collaborator

California Institute for Regenerative Medicine (CIRM) (Other)

Enrollment

Locations

Arms

72.6

Anticipated Duration (Months)

1.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant Rejection	Biological: MDR-101	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Total lymphoid irradiation and anti-thymocyte globulinTotal lymphoid irradiation and anti-thymocyte globulin

Masking:

None (Open Label)

Primary Purpose:

Prevention

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

Actual Study Start Date :

Mar 15, 2018

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Apr 1, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Functional immune tolerance defined as [Up to 36 months post-kidney transplant]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California San Diego Moores Cancer Center	La Jolla	California	United States	92037
2	Loma Linda University Medical Center	Loma Linda	California	United States	92354
3	USC	Los Angeles	California	United States	90033
4	Stanford University Medical Center	Stanford	California	United States	94305
5	University of Colorado Denver	Aurora	Colorado	United States	80045
6	Yale University	New Haven	Connecticut	United States	06519
7	Georgetown University Medical Center	Washington	District of Columbia	United States	20007
8	Mayo Clinic Hospital	Jacksonville	Florida	United States	32224
9	Loyola University Medical Center	Maywood	Illinois	United States	60153-3328
10	Mayo Clinic	Rochester	Minnesota	United States	55905
11	RWJBarnabas Health	Orange	New Jersey	United States	07052
12	Upstate University Hospital	Syracuse	New York	United States	13210
13	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
14	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
15	Baylor University Medical Center	Dallas	Texas	United States	75246
16	The Methodist Hospital	Houston	Texas	United States	77030
17	Intermountain Transplant Center	Murray	Utah	United States	84107
18	INOVA Fairfax Hospital	Fairfax	Virginia	United States	22031
19	University of Wisconsin School of Medicine	Madison	Wisconsin	United States	53792
20	CIUSSS de l'Est- de-l'Île-de-Montréal Installation Hopital Maisonneuve-Rosemont	Montréal	Quebec	Canada	H1T 2M4