Transplanted Organ Rejection
Conditions
Keywords
Kidney Transplant, Stem cell therapy, Anti-rejection medications, Living donor kidney transplant, Immune tolerance, Immunosuppression, Immunosuppressive medication, Organ transplant rejection
Brief summary
A randomized controlled study to evaluate the safety, efficacy, and overall benefit of FCR001 cell therapy in de novo living donor renal transplantation.
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.
Interventions
BIOLOGICALFCR001
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.
Sponsors
Talaris Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of FCR001 recipients who are free from immunosuppression (IS), without biopsy proven acute rejection (BPAR) at 24 months post-transplant | 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). |
Secondary
| 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 |
| Urinary protein and albumin excretion, estimated by urinary protein/creatinine and urinary albumin/creatinine ratios by treatment group | 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 |
| 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 |
| Incidence of BK viremia, viruria, infection, and nephropathy by treatment | Months 12, 24, 36 and 60 |
Countries
United States
Outcome results
None listed