A Safety and Efficacy Study of FCR001 vs Standard of Care in de Novo Living Donor Kidney Transplantation (FREEDOM-1)

A Randomized, Controlled, Multi-center, Safety and Efficacy Study of FCR001 Cell-based Therapy Relative to a Tacrolimus and Mycophenolate-based Regimen in de Novo Living Donor Renal Transplant Recipients, and Safety in FCR001 Donors

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

Study Overview

• Status: Terminated
• Conditions: Transplanted Organ Rejection
• Intervention / Treatment: Biological: FCR001

Detailed Description

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
• Enrollment (Actual): 15
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • The University of Michigan Hospitals & Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10065
      • New York-Presbyterian/Weill Cornell
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FCR001; 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.	Biological: FCR001; 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.; Other Names: Allogeneic stem cell transplant; Cell based therapy
No Intervention: Control; Standard induction therapy followed by a maintenance regimen of tacrolimus, mycophenolate, and +/- corticosteroids after kidney transplant. Control donors are not followed beyond randomization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	24 months post-transplant

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in renal function by Modification of Diet in Renal Disease (MDRD4) from post-transplant baseline (Month 1) to Month 24 in FCR001 recipients	24 months post-transplant
Proportion of FCR001 recipients free from IS, without BPAR, at Month 36 and 60	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	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	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	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	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	Months 12, 24, 36 and 60
Incidence of composite endpoint of BPAR, graft loss, or death and lost to follow-up, by treatment group	Months 12, 24, 36 and 60
Incidence of BPAR and treated BPAR by severity, type, and steroid-resistance, by treatment group	Months 12, 24, 36 and 60
Incidence of acute rejection	Months 12, 24, 36 and 60
Incidence of de novo donor-specific antibodies	Months 12, 24, 36 and 60
Incidence or worsening of abnormal histologic findings of cellular or antibody-mediated chronic rejection, chronic glomerulopathy, tubular atrophy and interstitial fibrosis, C4d, calcineurin inhibitor induced damage, disease recurrence, BK nephropathy	Months 12, 24, 36 and 60
Incidence of renal replacement therapy by treatment group	Months 12, 24, 36 and 60
Incidence of BPAR or eGFR <50 mL/min by treatment group	Months 12, 24, 36 and 60
Categorical distribution of eGFR according to chronic kidney disease CKD staging classification by treatment	Months 12, 24, 36 and 60
Incidence and severity of adverse events (AEs; including infections), serious adverse events (SAEs) and AEs leading to study and/or regimen discontinuation	Months 12, 24, 36 and 60
Incidence of BK viremia, viruria, infection, and nephropathy by treatment	Months 12, 24, 36 and 60
Incidence of the adverse events of special interest (proteinuria, neurotoxicity, anemia, diabetes, hypertension, dyslipidemia, opportunistic infections, major adverse cardiovascular events, and malignancies	Months 12, 24, 36 and 60
Urinary protein and albumin excretion, estimated by urinary protein/creatinine and urinary albumin/creatinine ratios by treatment group	Months 12, 24, 36 and 60
Subject quality of life according to 36-Item Short Form Health Survey (SF-36) will be analyzed descriptively by treatment group	Months 12, 24, 36 and 60
Subject quality of life according to End-Stage Renal Disease Symptom Checklist (ESRD-SCL) will be analyzed descriptively by treatment group	Months 12, 24, 36 and 60
Incidence and duration of hospitalization and readmission, according to type of ward/unit	Months 12, 24, 36 and 60
iBox predicted allograft survival	Months 12 and 24 post-transplant
Graft and patient survival and eGFR in FCR001 recipients who are only transiently chimeric	Month 24, 36, and 60
To describe the incidence and severity of AEs (including infections) and SAEs among FCR001 donors	Month 24, 36, and 60
Incidence of acute rejection, death, renal graft loss, and lost to follow-up between FCR001 recipients who did not achieve durable chimerism or the ability to wean or remain off immunosuppression vs. the control arm	Month 24, 36, and 60
The incidence of autologous infusions in FCR001 recipients	Month 6, 12, 24, 36, and 60
The incidence of engraftment syndrome in FCR001 recipients	Month 6, 12, 24, 36, and 60
The incidence of blood component transfusions in FCR001 recipients	Month 6, 12, 24, 36, and 60
The time to neutrophil and platelet recovery in FCR001 recipients	Month 6, 12, 24, 36, and 60
The incidence of acute and chronic Graft versus Host Disease (GvHD) in FCR001 recipients will be described	Month 6, 12, 24, 36, and 60
The incidence of donor chimerism and level of chimerism by study visit in FCR001 recipients will be described	Month 6, 12, 24, 36, and 60
The correlation of donor chimerism with freedom from IS)in FCR001 recipients will be described	Month 6, 12, 24, 36, and 60

Collaborators and Investigators

• Sponsor: Talaris Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2019
• Primary Completion (Actual): February 16, 2023
• Study Completion (Actual): February 16, 2023

Study Registration Dates

• First Submitted: June 13, 2019
• First Submitted That Met QC Criteria: June 20, 2019
• First Posted (Actual): June 24, 2019

Study Record Updates

• Last Update Posted (Actual): March 3, 2023
• Last Update Submitted That Met QC Criteria: March 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Immunosuppression; Kidney Transplant; Living donor kidney transplant; Immune tolerance; Stem cell therapy; Immunosuppressive medication; Anti-rejection medications; Organ transplant rejection
• Other Study ID Numbers: FCR001A2301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No