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

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ClinicalTrials.gov Identifier: NCT03605654
Recruitment Status : Not yet recruiting
First Posted : July 30, 2018
Last Update Posted : February 5, 2020
Sponsor:
Information provided by (Responsible Party):
Medeor Therapeutics, Inc.

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Kidney Transplant Rejection Biological: MDR-102 Drug: Standard Anti-Rejection Medications Phase 2 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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 172 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A low-dose Total Lymphoid Irradiation and anti- thymocyte globulin combined with a single infusion of MDR-102
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase 2/3, Prospective, Randomized, Multi-center, Open-Label, Controlled Trial to Assess the Efficacy and Safety of Cellular Immunotherapy With MDR-102 for Induction of Immune Quiescence™in Recipients of HLA-mismatched, Living Donor Kidney Transplants
Estimated Study Start Date : July 2020
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine


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
Biological: MDR-102
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
Drug: Standard Anti-Rejection Medications
Standard Anti-Rejection Medications that would be given to kidney transplant recipients who are outside the study

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
Biological: MDR-102
Enriched CD34+ hematopoietic stem cells and defined dose of CD3+ T-cells




Primary Outcome Measures :
  1. 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


  2. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03605654


Contacts
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Contact: Lenuta Micsa, MD 646-239-9748 lmicsa@medeortx.com
Contact: Suzanne Crowley, MS, BSN 321-266-9347 scrowley@medeortx.com

Sponsors and Collaborators
Medeor Therapeutics, Inc.
Investigators
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Study Director: Suzanne Crowley, MS, BSN Medeor Therapeutics

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Responsible Party: Medeor Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03605654    
Other Study ID Numbers: MDR-102-mMLK
First Posted: July 30, 2018    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No