Transplanted Organ Rejection Clinical Trial
— FREEDOM-1Official title:
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
| Verified date | March 2023 |
| Source | Talaris Therapeutics Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
A randomized controlled study to evaluate the safety, efficacy, and overall benefit of FCR001 cell therapy in de novo living donor renal transplantation.
| Status | Terminated |
| Enrollment | 15 |
| Est. completion date | February 16, 2023 |
| Est. primary completion date | February 16, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | The University of Michigan Hospitals & Health System | Ann Arbor | Michigan |
| United States | Northwestern Memorial Hospital | Chicago | Illinois |
| United States | The Ohio State University Wexner Medical Center | Columbus | Ohio |
| United States | Baylor University Medical Center | Dallas | Texas |
| United States | UT Southwestern Medical Center | Dallas | Texas |
| United States | Duke University Medical Center | Durham | North Carolina |
| United States | Mayo Clinic | Jacksonville | Florida |
| United States | Scripps Clinic | La Jolla | California |
| United States | University of Minnesota Medical Center | Minneapolis | Minnesota |
| United States | New York-Presbyterian/Weill Cornell | New York | New York |
| United States | University of Nebraska Medical Center | Omaha | Nebraska |
| United States | Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania |
| United States | Mayo Clinic | Phoenix | Arizona |
| United States | Oregon Health & Science University | Portland | Oregon |
| United States | Virginia Commonwealth University | Richmond | Virginia |
| United States | Mayo Clinic | Rochester | Minnesota |
| United States | University of California, San Francisco | San Francisco | California |
| United States | Georgetown University Hospital | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Talaris Therapeutics Inc. |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | 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 | ||
| Secondary | Proportion of FCR001 recipients free from IS, without BPAR, at Month 36 and 60 | Month 36 and 60 post transplant | ||
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | Incidence of composite endpoint of BPAR, graft loss or death, by treatment group | Months 12, 24, 36 and 60 | ||
| Secondary | Incidence of composite endpoint of BPAR, graft loss, or death and lost to follow-up, by treatment group | Months 12, 24, 36 and 60 | ||
| Secondary | Incidence of BPAR and treated BPAR by severity, type, and steroid-resistance, by treatment group | Months 12, 24, 36 and 60 | ||
| Secondary | Incidence of acute rejection | Months 12, 24, 36 and 60 | ||
| Secondary | Incidence of de novo donor-specific antibodies | Months 12, 24, 36 and 60 | ||
| Secondary | 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 | ||
| Secondary | Incidence of renal replacement therapy by treatment group | Months 12, 24, 36 and 60 | ||
| Secondary | Incidence of BPAR or eGFR <50 mL/min by treatment group | Months 12, 24, 36 and 60 | ||
| Secondary | Categorical distribution of eGFR according to chronic kidney disease CKD staging classification by treatment | Months 12, 24, 36 and 60 | ||
| Secondary | 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 | ||
| Secondary | Incidence of BK viremia, viruria, infection, and nephropathy by treatment | Months 12, 24, 36 and 60 | ||
| Secondary | 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 | ||
| Secondary | Urinary protein and albumin excretion, estimated by urinary protein/creatinine and urinary albumin/creatinine ratios by treatment group | Months 12, 24, 36 and 60 | ||
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | Incidence and duration of hospitalization and readmission, according to type of ward/unit | Months 12, 24, 36 and 60 | ||
| Secondary | iBox predicted allograft survival | Months 12 and 24 post-transplant | ||
| Secondary | Graft and patient survival and eGFR in FCR001 recipients who are only transiently chimeric | Month 24, 36, and 60 | ||
| Secondary | To describe the incidence and severity of AEs (including infections) and SAEs among FCR001 donors | Month 24, 36, and 60 | ||
| Secondary | 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 | ||
| Secondary | The incidence of autologous infusions in FCR001 recipients | Month 6, 12, 24, 36, and 60 | ||
| Secondary | The incidence of engraftment syndrome in FCR001 recipients | Month 6, 12, 24, 36, and 60 | ||
| Secondary | The incidence of blood component transfusions in FCR001 recipients | Month 6, 12, 24, 36, and 60 | ||
| Secondary | The time to neutrophil and platelet recovery in FCR001 recipients | Month 6, 12, 24, 36, and 60 | ||
| Secondary | The incidence of acute and chronic Graft versus Host Disease (GvHD) in FCR001 recipients will be described | Month 6, 12, 24, 36, and 60 | ||
| Secondary | 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 | ||
| Secondary | The correlation of donor chimerism with freedom from IS)in FCR001 recipients will be described | Month 6, 12, 24, 36, and 60 |