Kidney Transplantation
Conditions
Keywords
Selective allograft tolerance, Stem cell therapy, Living donor kidney transplant, Immune tolerance, Durable chimerism, Immunosuppression, Immunosuppressive medications, Organ transplant rejection, Anti-rejection medications
Brief summary
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
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.
Interventions
BIOLOGICALFCR001
Enriched hematopoietic stem cell infusion
Sponsors
Talaris Therapeutics Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
approximately 15 Donor/Recipient pairs
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Recipient age ≥18 years old. 2. Donor age ≥18 and ≤60 years old at the time of signing informed consent. 3. Recipient of a first kidney transplant from a living donor 3-12 months prior to signing informed consent. 4. 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). 5. 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): 1. Donor/recipient crossmatch positive at time of living donor kidney transplantation. 2. Recipient or donor with use of other investigational drugs within 30 days (or within 5 drug half-lives) of signing informed consent. 3. Recipient or donor with history of hypersensitivity to any of the study drugs or drugs of similar chemical classes. 4. Recipient and donor who are identical twins. 5. Pregnant or nursing (lactating) woman. 6. 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. 7. Recipient or donor with known bone marrow aplasia. Main
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| Incidence of BK viremia, viruria, infection, and nephropathy | From informed consent to 12 months, 24 months and 60 months |
Countries
United States
Outcome results
None listed