A Safety and Efficacy Study of FCR001 vs Standard of Care in de Novo Living Donor Kidney Transplantation

Phase 3TerminatedNCT03995901

Talaris Therapeutics Inc.15 enrolled

Overview

A randomized controlled study to evaluate the safety, efficacy, and overall benefit of FCR001 cell therapy in de novo living donor renal transplantation.

The purpose of this randomized (2:1) controlled study is to evaluate the safety, efficacy and overall benefit of FCR001 cell therapy in first or second de novo living donor renal transplantation relative to a standard-of-care control immunosuppression regimen of antibody induction, tacrolimus, mycophenolate, and corticosteroids.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Transplanted Organ Rejection

Interventions

FCR001BIOLOGICAL

FCR001 is a cryopreserved allogeneic stem cell therapy derived from mobilized peripheral blood of the kidney donor that is delivered as a single dose with a non- myeloablative conditioning regimen. FCR001 contains the donor's CD34+ cells, facilitating cells, and αβ T cells.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Main Inclusion Criteria: * Recipient age ≥18 years. * Donor age ≥18 and ≤60 years at time of signing informed consent. * Recipients of a first or second living donor kidney transplant * Donor willing to undergo mobilization, apheresis and 12-month safety follow-up and meet all local standard eligibility criteria to donate stem cells for allogeneic transplantation. * Recipient meets all local standard eligibility criteria for allogeneic stem cell transplant. * Donors must be deemed eligible as per the requirements of 21CFR1271. Main Recipient and Donor Exclusion Criteria: * Recipient and donor who are identical twins. * Recipient or donor with history of malignancy or premalignant syndrome (e.g., myelodysplastic syndrome, monoclonal gammopathy of renal significance \[MGRS\], monoclonal gammopathy of unknown significance \[MGUS\]) of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. * Recipient or donor with known bone marrow aplasia. Main Recipient-only Exclusion Criteria: * Multi-organ or stem cell transplant recipient. * Calculated panel reactive antibodies \>80%. * Recipient is blood type ABO incompatible with donor. * Presence of donor-specific antibodies (DSA) (positive result) at any time pre-transplant. * Recipient who is human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) positive. * Recipient with any baseline condition requiring or anticipated will require chronic or intermittent use of systemic steroids or other IS (eg, autoimmune disease, asthma) throughout the course of the study. * Recipient with a BMI \< 18 or \> 35 kg/m2. * Recipient requiring systemic anticoagulation, (eg, for hyper-coagulation disorders, deep vein thrombosis, atrial fibrillation) that cannot be temporarily interrupted which would preclude renal biopsy. Main Donor-only Exclusion Criteria: * Biologically unrelated (i.e., no genetic relationship) female donor transplant to male recipient.

Locations (18)

Mayo Clinic

Phoenix, Arizona, United States

Scripps Clinic

La Jolla, California, United States

Outcomes

Primary Outcomes

Proportion of FCR001 recipients who are free from immunosuppression (IS), without biopsy proven acute rejection (BPAR) at 24 months post-transplant

Free from IS is defined as not taking any immunosuppression medications and not having to take immunosuppression medications since their withdrawal. Biopsy proven acute rejection is defined as Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018).

Time frame: 24 months post-transplant

Secondary Outcomes

Change in renal function by Modification of Diet in Renal Disease (MDRD4) from post-transplant baseline (Month 1) to Month 24 in FCR001 recipients

Time frame: 24 months post-transplant

Proportion of FCR001 recipients free from IS, without BPAR, at Month 36 and 60

Time frame: Month 36 and 60 post transplant

Allograft function (eGFR by MDRD4) and change in eGFR from Month 1 to Month 24, 36, and Month 60, by treatment

Time frame: Month 1 (post-transplant) to Month 24, 36, and Month 60

Slope and difference in slope of estimated glomerular filtration rate (eGFR) by Modification of Diet in Renal Disease (MDRD4) over time to Month 24, 36, and 60, by treatment

Time frame: Month 24, 36, and 60

Allograft function (eGFR) and change in renal allograft function from Month 1 to Months 24, 36 and 60 by treatment group, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula

Time frame: Month 1 (post transplant) to Month 24, 36, and Month 60

Time to the event for the composite of BPAR, graft loss, death or lost to follow-up and for each component, by treatment group

Data from ClinicalTrials.gov

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University of California, San Francisco

San Francisco, California, United States

Georgetown University Hospital

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

Mayo Clinic

Jacksonville, Florida, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

The University of Michigan Hospitals & Health System

Ann Arbor, Michigan, United States

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

...and 8 more locations

Time frame: Month 1 (post transplant) to Month 6, 12, 24, 36, and 60

Incidence of composite endpoint of BPAR, graft loss or death, by treatment group