Brief Summary
The purpose of this open-label, randomized, active-comparator-controlled study is to determine the efficacy and safety of frexalimab subcutaneous administrations up to 5 years compared to tacrolimus capsules in adults undergoing kidney transplantation. Participants aged 18 to 70 years who have low-to-moderate immunologic risk of graft rejection and receive their first kidney transplant are eligible if they meet all inclusion and no exclusion criteria. Study details include:
* The study and treatment duration will be up to approximately 5 years.
* The number of visits will be approximately 38.
* The study and treatment duration will be up to approximately 5 years.
* The number of visits will be approximately 38.
Brief Title
A Study to Investigate the Efficacy and Safety of Frexalimab Versus Tacrolimus in Adults Undergoing Kidney Transplantation
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
800-633-1610
Central Contact Phone Ext
option 6
Central Contact Email
Contact-US@sanofi.com
Completion Date
Completion Date Type
Estimated
Conditions
KIDNEY TRANSPLANT REJECTION
Eligibility Criteria
Inclusion Criteria:
* Participants who are scheduled to receive their first kidney transplant from a living or deceased donor.
* Participants with low to moderate immunological risk.
Exclusion Criteria:
* Deceased donor kidney graft qualified as expanded criteria donor or donor after cardiac death.
* Positive T or B cell crossmatch, or positive virtual crossmatch per local practice at screening.
* Participants receiving a kidney graft from HLA-identical living-related donors, or have current or previous solid organ, cell, or multi-organ transplantation, or paired kidney transplantation.
* Participants whose primary causes of ESKD are idiopathic FSGS, C3 glomerulopathy, lupus nephritis, or thrombotic microangiopathy
* Evidence of active or latent TB, HIV, HBV or HCV infection.
* Participants who have known genetically predisposed thrombophilia, have history of thromboembolic events, or who need long-term anti-coagulation therapy.
* Participants who have severe medical co-morbidities, active infection, or severely limited life expectancy due to underlying medical conditions that are generally precluded from kidney transplant.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
* Participants who are scheduled to receive their first kidney transplant from a living or deceased donor.
* Participants with low to moderate immunological risk.
Exclusion Criteria:
* Deceased donor kidney graft qualified as expanded criteria donor or donor after cardiac death.
* Positive T or B cell crossmatch, or positive virtual crossmatch per local practice at screening.
* Participants receiving a kidney graft from HLA-identical living-related donors, or have current or previous solid organ, cell, or multi-organ transplantation, or paired kidney transplantation.
* Participants whose primary causes of ESKD are idiopathic FSGS, C3 glomerulopathy, lupus nephritis, or thrombotic microangiopathy
* Evidence of active or latent TB, HIV, HBV or HCV infection.
* Participants who have known genetically predisposed thrombophilia, have history of thromboembolic events, or who need long-term anti-coagulation therapy.
* Participants who have severe medical co-morbidities, active infection, or severely limited life expectancy due to underlying medical conditions that are generally precluded from kidney transplant.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Inclusion Criteria
Inclusion Criteria:
* Participants who are scheduled to receive their first kidney transplant from a living or deceased donor.
* Participants with low to moderate immunological risk.
* Participants who are scheduled to receive their first kidney transplant from a living or deceased donor.
* Participants with low to moderate immunological risk.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
70 Years
Minimum Age
18 Years
NCT Id
NCT07412470
Org Class
Industry
Org Full Name
Sanofi
Org Study Id
EFC18554
Overall Status
Recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Seamless Phase 2/3 Randomized, Open-label Study to Investigate Efficacy and Safety of Frexalimab Versus Tacrolimus in Adult Kidney Transplant Recipients
Primary Outcomes
Outcome Description
BPAR is defined as biopsy confirmed T cell mediated and antibody mediated rejection as categorized by BANFF 2022; graft loss is defined as the first date the patients meet any of the following criteria: chronic dialysis for a least 56 days, day of allograft nephrectomy, or day of re-transplant.
Outcome Measure
Composite efficacy failure rate (BPAR, graft loss, and death) by 1 year post kidney transplantation
Outcome Time Frame
by 1 year
Secondary Ids
Secondary Id
2025-521521-33-00
Secondary Outcomes
Outcome Description
eGFR will be calculated with CKD-EPI 2021 formula, based on the creatinine value, age, and gender of the participant
Outcome Time Frame
at 1 year
Outcome Measure
eGFR at 1 year post kidney transplantation
Outcome Description
eGFR will be calculated with CKD-EPI 2021 formula, based on the creatinine value, age, and gender of the participant
Outcome Time Frame
at 6 months, 2 years, 3 years, 4 years, and 5 years
Outcome Measure
eGFR at 6 months, 2 years, 3 years, 4 years, and 5 years post kidney transplantation
Outcome Time Frame
from Month 3 over time up to 5 years
Outcome Measure
Change of eGFR from Month 3 over time up to 5 years post kidney transplantation
Outcome Time Frame
at 1, 2, 3, and 5 years
Outcome Measure
Participant status of eGFR > 60 mL/min/1.73 m2 at 1, 2, 3, and 5 years post kidney transplantation
Outcome Time Frame
from Month 3 to 12
Outcome Measure
Participant status of eGFR < 60 mL/min/1.73 m² at Month 12 or with a > 10 mL/min/1.73 m² decrease in eGFR from Month 3 to 12
Outcome Description
defined as protein concentration in the urine
Outcome Time Frame
at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years
Outcome Measure
Proteinuria at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years post kidney transplantation
Outcome Time Frame
at 1 year
Outcome Measure
iBox score at 1 year post kidney transplantation
Outcome Time Frame
at 5 years
Outcome Measure
Composite of participant and graft survival at 5 years post kidney transplantation
Outcome Time Frame
at 6 months, 1 year, 2 years, 3 years, and 4 years
Outcome Measure
Composite of participant and graft survival over time and at 6 months, 1 year, 2 years, 3 years, and 4 years post kidney transplantation
Outcome Time Frame
at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years
Outcome Measure
Death-censored graft survival over time and at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years post kidney transplantation (including the causes of graft loss)
Outcome Time Frame
at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years
Outcome Measure
Participant survival over time and at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years post kidney transplantation (including the causes of death)
Outcome Time Frame
up to 5 years
Outcome Measure
Incidence of BPAR (yearly and cumulative) up to 5 years post kidney transplantation
Outcome Time Frame
up to 5 years
Outcome Measure
Time to first BPAR
Outcome Time Frame
at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years
Outcome Measure
Incidence of graft rejection at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years post kidney transplantation
Outcome Time Frame
up to 5 years
Outcome Measure
Incidence of rejection episodes with clinical resolution up to 5 years post kidney transplantation
Outcome Time Frame
by 6 months
Outcome Measure
Composite efficacy failure rate (BPAR, graft loss, and death) by 6 months post kidney transplantation
Outcome Time Frame
at 1 year
Outcome Measure
Incidence of de novo donor-specific antibodies at 1 year post kidney transplantation
Outcome Time Frame
at 5 years
Outcome Measure
Incidence of de novo donor-specific antibodies at 5 years post kidney transplantation
Outcome Time Frame
until 5 years
Outcome Measure
Participants with AEs, SAEs, AEs leading to permanent study intervention discontinuation, AESIs, and PCSAs in laboratory tests, ECG, and vital signs during the study period
Outcome Time Frame
until 5 years
Outcome Measure
Participants with medical device AEs, ADEs, medical device SAEs, SADEs, and device deficiencies during the study period
Outcome Time Frame
at Months 1, 2, 3, 4, 5, 6 and then every 6 months until the end of the study
Outcome Measure
Side effects of immunosuppressive therapy evaluated by MTSOSD-59R score at Months 1, 2, 3, 4, 5, 6 and then every 6 months until the end of the study
Outcome Time Frame
up to 1 year
Outcome Measure
Frexalimab plasma concentration over time
Outcome Time Frame
until 5 years
Outcome Measure
Incidence of ADA
Outcome Time Frame
until 5 years
Outcome Measure
Incidence of new-onset diabetes post kidney transplantation
Outcome Time Frame
until 5 years
Outcome Measure
Incidence of hypertension, anti-hypertensive regimen, and systolic and diastolic blood pressure
Outcome Time Frame
until 5 years
Outcome Measure
Incidence of dyslipidemia, lipid-lowering regimen, and measures of dyslipidemia, including serum TG and total, non-HDL, LDL, and HDL cholesterol
Outcome Time Frame
until 5 years
Outcome Measure
Titer of ADA
Outcome Time Frame
until 5 years
Outcome Measure
Persistence of ADA
Outcome Time Frame
until 5 years
Outcome Measure
Prevalence of hypertension, anti-hypertensive regimen, and systolic and diastolic blood pressure
Outcome Time Frame
until 5 years
Outcome Measure
Prevalence of dyslipidemia, lipid-lowering regimen, and measures of dyslipidemia, including serum TG and total, non-HDL, LDL, and HDL cholesterol
Outcome Time Frame
At 1 year
Outcome Measure
Incidence of chronic allograft nephropathy at 1 year
Outcome Time Frame
At 3 months, 1, 2, 3, 4, and 5 years
Outcome Measure
HbA1c levels at 3 months, 1, 2, 3, 4, and 5 years post transplantation in non-diabetic participants at baseline.
Outcome Time Frame
at 3 months, 1, 2, 3, 4, and 5 years
Outcome Measure
Proportion of baseline non-diabetic participants using insulin and/other anti-diabetic medication at 3 months, 1, 2, 3, 4, and 5 years post transplantation.
Outcome Time Frame
at 1, 2, 3, 4, 5-year
Outcome Measure
Incidence of the composite cardiac and cerebrovascular events (cardiovascular death, myocardial infarction, ischemic stroke, and revascularization [surgical or percutaneous] procedures) at 1, 2, 3, 4, 5-year post transplantation.
Outcome Time Frame
at 1 year
Outcome Measure
Framingham cardiovascular risk score at 1 year post transplantation
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
70
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Enver Akalin
Investigator Email
eakalin@montefiore.org
Investigator Phone
718-920-4815
Investigator Department
Medicine
Investigator Division
Nephrology
Investigator Sponsor Organization
External
Study Department
Medicine
Study Division
Nephrology
MeSH Terms
TACROLIMUS
ANTILYMPHOCYTE SERUM
MYCOPHENOLIC ACID
METHYLPREDNISOLONE
PREDNISONE
MACROLIDES
LACTONES
ORGANIC CHEMICALS
IMMUNE SERA
ANTIBODIES
IMMUNOGLOBULINS
IMMUNOPROTEINS
BLOOD PROTEINS
PROTEINS
AMINO ACIDS, PEPTIDES, AND PROTEINS
SERUM GLOBULINS
GLOBULINS
BIOLOGICAL PRODUCTS
COMPLEX MIXTURES
CAPROATES
ACIDS, ACYCLIC
CARBOXYLIC ACIDS
FATTY ACIDS
LIPIDS
PREDNISOLONE
PREGNADIENETRIOLS
PREGNADIENES
PREGNANES
STEROIDS
FUSED-RING COMPOUNDS
POLYCYCLIC COMPOUNDS
PREGNADIENEDIOLS