A Safety and Efficacy Study of FCR001 Cell Therapy in Previously Transplanted Living Donor Kidney Recipients

Study Overview
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Brief Summary
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An open-label study to assess the safety, tolerability, and efficacy of FCR001 cell therapy in adult recipients 3-12 months after kidney transplantation from a living donor.

Detailed Description
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The purpose of this study is to assess the safety, tolerability, preliminary efficacy, and overall benefit of FCR001 cell therapy in previously transplanted recipients of a kidney from a living donor. FCR001 is a novel, cryopreserved allogeneic somatic cell therapy, derived from mobilized peripheral blood mononuclear cells from the same donor as the allograft, and containing hematopoietic progenitor cells, facilitating cells, and αβ T cells. The rationale is to establish durable chimerism and donor-specific tolerance in the recipient enabling freedom from chronic immunosuppression (IS) and its associated toxicities.

Official Title
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A Single-arm, Multi-center, Exploratory Safety and Efficacy Study of FCR001 Cell-based Therapy to Induce Donor-specific Tolerance in Previously Transplanted Recipients of a Kidney From a Living Donor, and Safety in FCR001 Donors

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Biological: FCR001


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Recipient age ≥18 years old. Donor age ≥18 and ≤60 years old at the time of signing informed consent. Recipient of a first kidney transplant from a living donor 3-12 months prior to signing informed consent. Stable renal allograft function ≥60 mL/min/1.73m^2 prior to screening (defined as <25% decrease in eGFR (by Modification of Diet in Renal Disease formula [MDRD4]) between the last 2 consecutive visits and per investigator judgment). Donor between 3 weeks and 12 months after kidney donation, willing to undergo mobilization, apheresis, and 12-month safety follow-up. Main Exclusion Criteria (Recipient and Donor): Donor/recipient crossmatch positive at time of living donor kidney transplantation. Recipient or donor with use of other investigational drugs within 30 days (or within 5 drug half-lives) of signing informed consent. Recipient or donor with history of hypersensitivity to any of the study drugs or drugs of similar chemical classes. Recipient and donor who are identical twins. Pregnant or nursing (lactating) woman. Recipient or donor with history of malignancy or premalignant syndrome (e.g., myelodysplastic syndrome, monoclonal gammopathy of renal significance [MGRS], monoclonal gammopathy of unknown significant [MGUS]) of any organ system (other than localized excised non-melanomatous lesions 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 Exclusion Criteria (Recipient-Only): Multi-organ or cell transplant recipient. Blood type ABO incompatible with donor. Positive donor-specific antibody (DSA) at any time pre- or post-transplant (to be confirmed within 30 days prior to FCR001 infusion). Panel Reactive Antibodies (PRA) >80% at the time of living donor kidney transplantation. Induction with alemtuzumab at the time of living donor kidney transplantation. History of acute rejection (biopsy-proven or suspected and treated) or recurrent kidney disease following living donor kidney transplantation. Findings consistent with acute rejection or recurrent disease on the Screening biopsy. Demonstrated intolerance to maintenance immunosuppression with tacrolimus and MMF or MPS. Being maintained on oral corticosteroids (prednisone >10 mg/day or equivalent). Positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV). Recipients with history of HCV infection may participate if there is a documented history of treatment with an anti-HCV agent and either one (1) documented negative PCR at least three (3) months after last dose of treatment, or two (2) documented negative PCRs at least 2 weeks apart over a maximum of 4 weeks. Positive for BKV, CMV, or EBV by PCR at screening. Having any baseline condition requiring or anticipated to require chronic or intermittent use of systemic steroids or other IS (e.g., autoimmune disease, asthma) throughout the course of the study. Having a body mass index (BMI) < 18 or > 35 kg/m^2. Requiring systemic anticoagulation, (e.g., for hypercoagulation disorders, deep vein thrombosis, atrial fibrillation) that cannot be temporarily interrupted with would preclude renal biopsy. Having contraindication to TBI according to local radiologist. History of autologous or allogeneic hematopoietic progenitor or mesenchymal stem cell transplant prior to signing informed consent. Main Exclusion Criteria (Donor-Only): Biologically unrelated (i.e., no genetic relationship) female donor transplant to male recipient.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: approximately 15 Donor/Recipient pairs
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FCR001<br>Recipients 3-12 months post-living kidney transplantation undergo non-myeloablative conditioning followed by infusion of an enriched hematopoietic stem cell product derived from the same living donor's peripheral blood stem cells | Biological: FCR001<br>* Enriched hematopoietic stem cell infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of FCR recipients (FCR-R) who are free from immunosuppression (IS), without biopsy-proven acute rejection (BPAR), at 24 months post-FCR001 infusion |  | From infusion to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in renal function (estimated Glomerular Filtration Rate [eGFR] by Modification of Diet in Renal Disease [MDRD4]) from baseline (Day 1, prior to FCR001 infusion) to Month 24 in FCR recipients |  | From Day 1 prior to infusion to 24 months | 
| Renal allograft function (eGFR by MDRD4) |  | From infusion to 24 months and 60 months | 
| Change in renal allograft function over time by MDRD4 |  | From infusion to 24 months and 60 months | 
| Renal allograft function (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula |  | From infusion to 24 months and 60 months | 
| Change in renal allograft function over time by CKD-EPI |  | From infusion to 24 months and 60 months | 
| Time to event for the composite of BPAR, renal graft loss, death, or lost to follow-up and each component |  | From infusion to 60 months | 
| Incidence of composite endpoint of BPAR, renal graft loss, or death |  | From infusion to 12 months, 24 months and 60 months | 
| Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and AEs leading to study and/or regimen discontinuation |  | From informed consent to 12 months, 24 months and 60 months | 
| Incidence of BK viremia, viruria, infection, and nephropathy |  | From informed consent to 12 months, 24 months and 60 months | 
| Incidence of donor chimerism by visit |  | From infusion to 60 months | 
| Incidence of acute and chronic GvHD |  | From infusion to 60 months | 
| Incidence of engraftment syndrome |  | From infusion to 60 months | 
| Incidence of recipient autologous apheresis product infusion |  | From infusion to 60 months | 
| Renal graft survival for recipients transiently chimeric |  | From infusion to 60 months | 
| Incidence of composite endpoint of BPAR, death, renal graft loss, or lost to follow-up in FCR-R who did not achieve durable chimerism or able to wean or remain off IS |  | From infusion to 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Selective allograft tolerance, Stem cell therapy, Living donor kidney transplant, Immune tolerance, Durable chimerism, Immunosuppression, Immunosuppressive medications, Organ transplant rejection, Anti-rejection medications