Clinical trial NCT03995901: A Safety and Efficacy Study of FCR001 vs Standard of Care in de Novo Living Donor Kidney Transplantation
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Transplanted Organ Rejection
Keywords: Kidney Transplant
Stem cell therapy
Anti-rejection medications
Living donor kidney transplant
Immune tolerance
Immunosuppression
Immunosuppressive medication
Organ transplant rejection
Lead sponsor: Talaris Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2019-06-24
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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 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.

Primary outcomes:
measure: Proportion of FCR001 recipients who are free from immunosuppression (IS), without biopsy proven acute rejection (BPAR) at 24 months post-transplant
timeFrame: 24 months post-transplant
Secondary outcomes:
measure: Change in renal function by Modification of Diet in Renal Disease (MDRD4) from post-transplant baseline (Month 1) to Month 24 in FCR001 recipients
timeFrame: 24 months post-transplant
measure: Proportion of FCR001 recipients free from IS, without BPAR, at Month 36 and 60
timeFrame: Month 36 and 60 post transplant
measure: Allograft function (eGFR by MDRD4) and change in eGFR from Month 1 to Month 24, 36, and Month 60, by treatment
timeFrame: Month 1 (post-transplant) to Month 24, 36, and Month 60
measure: 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
timeFrame: Month 24, 36, and 60
measure: 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
timeFrame: Month 1 (post transplant) to Month 24, 36, and Month 60
measure: Time to the event for the composite of BPAR, graft loss, death or lost to follow-up and for each component, by treatment group
timeFrame: Month 1 (post transplant) to Month 6, 12, 24, 36, and 60
measure: Incidence of composite endpoint of BPAR, graft loss or death, by treatment group
timeFrame: Months 12, 24, 36 and 60
measure: Incidence of composite endpoint of BPAR, graft loss, or death and lost to follow-up, by treatment group
timeFrame: Months 12, 24, 36 and 60
measure: Incidence of BPAR and treated BPAR by severity, type, and steroid-resistance, by treatment group
timeFrame: Months 12, 24, 36 and 60
measure: Incidence of acute rejection
timeFrame: Months 12, 24, 36 and 60
measure: Incidence of de novo donor-specific antibodies
timeFrame: Months 12, 24, 36 and 60
measure: 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
timeFrame: Months 12, 24, 36 and 60
measure: Incidence of renal replacement therapy by treatment group
timeFrame: Months 12, 24, 36 and 60
measure: Incidence of BPAR or eGFR <50 mL/min by treatment group
timeFrame: Months 12, 24, 36 and 60
measure: Categorical distribution of eGFR according to chronic kidney disease CKD staging classification by treatment
timeFrame: Months 12, 24, 36 and 60
measure: Incidence and severity of adverse events (AEs; including infections), serious adverse events (SAEs) and AEs leading to study and/or regimen discontinuation
timeFrame: Months 12, 24, 36 and 60
measure: Incidence of BK viremia, viruria, infection, and nephropathy by treatment
timeFrame: Months 12, 24, 36 and 60
measure: Incidence of the adverse events of special interest (proteinuria, neurotoxicity, anemia, diabetes, hypertension, dyslipidemia, opportunistic infections, major adverse cardiovascular events, and malignancies
timeFrame: Months 12, 24, 36 and 60
measure: Urinary protein and albumin excretion, estimated by urinary protein/creatinine and urinary albumin/creatinine ratios by treatment group
timeFrame: Months 12, 24, 36 and 60
measure: Subject quality of life according to 36-Item Short Form Health Survey (SF-36) will be analyzed descriptively by treatment group
timeFrame: Months 12, 24, 36 and 60
measure: Subject quality of life according to End-Stage Renal Disease Symptom Checklist (ESRD-SCL) will be analyzed descriptively by treatment group
timeFrame: Months 12, 24, 36 and 60
measure: Incidence and duration of hospitalization and readmission, according to type of ward/unit
timeFrame: Months 12, 24, 36 and 60
measure: iBox predicted allograft survival
timeFrame: Months 12 and 24 post-transplant
measure: Graft and patient survival and eGFR in FCR001 recipients who are only transiently chimeric
timeFrame: Month 24, 36, and 60
measure: To describe the incidence and severity of AEs (including infections) and SAEs among FCR001 donors
timeFrame: Month 24, 36, and 60
measure: 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
timeFrame: Month 24, 36, and 60
measure: The incidence of autologous infusions in FCR001 recipients
timeFrame: Month 6, 12, 24, 36, and 60
measure: The incidence of engraftment syndrome in FCR001 recipients
timeFrame: Month 6, 12, 24, 36, and 60
measure: The incidence of blood component transfusions in FCR001 recipients
timeFrame: Month 6, 12, 24, 36, and 60
measure: The time to neutrophil and platelet recovery in FCR001 recipients
timeFrame: Month 6, 12, 24, 36, and 60
measure: The incidence of acute and chronic Graft versus Host Disease (GvHD) in FCR001 recipients will be described
timeFrame: Month 6, 12, 24, 36, and 60
measure: The incidence of donor chimerism and level of chimerism by study visit in FCR001 recipients will be described
timeFrame: Month 6, 12, 24, 36, and 60
measure: The correlation of donor chimerism with freedom from IS)in FCR001 recipients will be described
timeFrame: Month 6, 12, 24, 36, and 60
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Ann Arbor
country: United States
facility: The University of Michigan Hospitals & Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: New York-Presbyterian/Weill Cornell
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
References: