Kidney Transplant Rejection
Conditions
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.
Interventions
DRUGFrexalimab
Pharmaceutical form:Solution for injection-Route of administration:IV
DRUGTacrolimus
Pharmaceutical form:Capsule-Route of administration:Oral
Pharmaceutical form:Solution for injection-Route of administration:IV
DRUGmycophenolate mofetil
Pharmaceutical form:Tablet or capsule-Route of administration:Oral
Pharmaceutical form:Tablet-Route of administration:Oral
DRUGmethylprednisolone
Pharmaceutical form:Solution for injection-Route of administration:IV
DRUGprednisone
Pharmaceutical form:Tablet-Route of administration:Oral
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
\[Specify Complex Masking\]
Intervention model description
\[Specify Complex Design\]
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite efficacy failure rate (BPAR, graft loss, and death) by 1 year post kidney transplantation | by 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| eGFR at 1 year post kidney transplantation | at 1 year | eGFR will be calculated with CKD-EPI 2021 formula, based on the creatinine value, age, and gender of the participant |
| eGFR at 6 months, 2 years, 3 years, 4 years, and 5 years post kidney transplantation | at 6 months, 2 years, 3 years, 4 years, and 5 years | eGFR will be calculated with CKD-EPI 2021 formula, based on the creatinine value, age, and gender of the participant |
| Change of eGFR from Month 3 over time up to 5 years post kidney transplantation | from Month 3 over time up to 5 years | — |
| Participant status of eGFR > 60 mL/min/1.73 m2 at 1, 2, 3, and 5 years post kidney transplantation | at 1, 2, 3, and 5 years | — |
| 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 | from Month 3 to 12 | — |
| Proteinuria at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years post kidney transplantation | at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years | defined as protein concentration in the urine |
| iBox score at 1 year post kidney transplantation | at 1 year | — |
| Composite of participant and graft survival at 5 years post kidney transplantation | at 5 years | — |
| Composite of participant and graft survival over time and at 6 months, 1 year, 2 years, 3 years, and 4 years post kidney transplantation | at 6 months, 1 year, 2 years, 3 years, and 4 years | — |
| 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) | at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years | — |
| 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) | at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years | — |
| Incidence of BPAR (yearly and cumulative) up to 5 years post kidney transplantation | up to 5 years | — |
| Time to first BPAR | up to 5 years | — |
| Incidence of graft rejection at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years post kidney transplantation | at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years | — |
| Incidence of rejection episodes with clinical resolution up to 5 years post kidney transplantation | up to 5 years | — |
| Composite efficacy failure rate (BPAR, graft loss, and death) by 6 months post kidney transplantation | by 6 months | — |
| Incidence of de novo donor-specific antibodies at 1 year post kidney transplantation | at 1 year | — |
| Incidence of de novo donor-specific antibodies at 5 years post kidney transplantation | at 5 years | — |
| 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 | until 5 years | — |
| Participants with medical device AEs, ADEs, medical device SAEs, SADEs, and device deficiencies during the study period | until 5 years | — |
| 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 | at Months 1, 2, 3, 4, 5, 6 and then every 6 months until the end of the study | — |
| Frexalimab plasma concentration over time | up to 1 year | — |
| Incidence of ADA | until 5 years | — |
| Incidence of new-onset diabetes post kidney transplantation | until 5 years | — |
| Incidence of hypertension, anti-hypertensive regimen, and systolic and diastolic blood pressure | until 5 years | — |
| Incidence of dyslipidemia, lipid-lowering regimen, and measures of dyslipidemia, including serum TG and total, non-HDL, LDL, and HDL cholesterol | until 5 years | — |
| Titer of ADA | until 5 years | — |
| Persistence of ADA | until 5 years | — |
| Prevalence of hypertension, anti-hypertensive regimen, and systolic and diastolic blood pressure | until 5 years | — |
| Prevalence of dyslipidemia, lipid-lowering regimen, and measures of dyslipidemia, including serum TG and total, non-HDL, LDL, and HDL cholesterol | until 5 years | — |
Countries
Australia, China
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
Outcome results
None listed