Clinical trial NCT03605654: Cellular Immunotherapy in Recipients of Human Leukocyte Antigen (HLA)-Mismatched, Living Donor Kidney Transplants
Official title: A Phase 2/3, Prospective, Randomized, Multi-center, Open-Label, Controlled Trial to Assess the Efficacy & Safety of Cellular Immunotherapy With MDR-102 for Induction of Immune Quiescence™in Recipients of HLA-mismatched, LD Kidney Transplants
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Kidney Transplant Rejection
Lead sponsor: Medeor Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A low-dose Total Lymphoid Irradiation and anti- thymocyte globulin combined with a single infusion of MDR-102
Primary purpose: PREVENTION

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.

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.

Eligibility 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

Primary outcomes:
measure: Phase 2 Primary Outcome: Achievement of persistent mixed chimerism and withdrawal of at least one Immunosuppression drug for a minimum of 6 months
timeFrame: 6 months
measure: Phase 3 Primary Outcome: proportion of subjects achieving immune quiescence
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Medeor Therapeutics
name: Lenuta Micsa, MD
role: STUDY_DIRECTOR
References: