A Study to Investigate the Efficacy and Safety of Frexalimab Versus Tacrolimus in Adults Undergoing Kidney Transplantation (FREXERA)

A Seamless Phase 2/3 Randomized, Open-label Study to Investigate Efficacy and Safety of Frexalimab Versus Tacrolimus in Adult Kidney Transplant Recipients

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.

Study Overview

• Status: Recruiting
• Conditions: Kidney Transplant Rejection
• Intervention / Treatment: Drug: Frexalimab; Drug: Frexalimab; Drug: rabbit anti-thymocyte globulin; Drug: mycophenolate mofetil; Drug: mycophenolate sodium; Drug: methylprednisolone; Drug: prednisone; Drug: Tacrolimus

• Study Type: Interventional
• Enrollment (Estimated): 526
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: contact-us@sanofi.com

Study Locations

• Australia
  • Sydney, Australia, 2050
    • Recruiting
    • Investigational Site Number : 0360003
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Recruiting
      • Investigational Site Number : 0360001
• Chile
  • Reg Metropolitana de Santiago
    • Santiago, Reg Metropolitana de Santiago, Chile, 8330034
      • Recruiting
      • Investigational Site Number : 1520004
• China
  • Chengdu, China, 610041
    • Recruiting
    • Investigational Site Number : 1560003
  • Jinan, China, 250014
    • Recruiting
    • Investigational Site Number : 1560012
  • Nanchang, China, 330006
    • Recruiting
    • Investigational Site Number : 1560017
  • Nanning, China, 530007
    • Recruiting
    • Investigational Site Number : 1560008
  • Shanghai, China, 200127
    • Recruiting
    • Investigational Site Number : 1560001
  • Wuhan, China, 430030
    • Recruiting
    • Investigational Site Number : 1560006
• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Investigational Site Number : 2080001
• Israel
  • Ramat Gan, Israel, 5262100
    • Recruiting
    • Investigational Site Number : 3760002
• Spain
  • Málaga, Spain, 29010
    • Recruiting
    • Investigational Site Number : 7240005
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Recruiting
      • Investigational Site Number : 7240001
  • Catalunya [Cataluña]
    • Barcelona, Catalunya [Cataluña], Spain, 08036
      • Recruiting
      • Investigational Site Number : 7240007
    • L'Hospitalet de Llobregat, Catalunya [Cataluña], Spain, 08907
      • Recruiting
      • Investigational Site Number : 7240003
• United Kingdom
  • England
    • Birmingham, England, United Kingdom, B15 2TH
      • Recruiting
      • Investigational Site Number : 8260001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tacrolimus	Drug: rabbit anti-thymocyte globulin; Pharmaceutical form:Solution for injection-Route of administration:IV; Drug: mycophenolate mofetil; Pharmaceutical form:Tablet or capsule-Route of administration:Oral; Drug: mycophenolate sodium; Pharmaceutical form:Tablet-Route of administration:Oral; Drug: methylprednisolone; Pharmaceutical form:Solution for injection-Route of administration:IV; Drug: prednisone; Pharmaceutical form:Tablet-Route of administration:Oral; Drug: Tacrolimus; Pharmaceutical form:Capsule-Route of administration:Oral
Experimental: Frexalimab; Frexalimab: the first dose of frexalimab will be given intravenously, the maintenance dose of frexalimab will be administered subcutaneously via on-body delivery system(OBDS)	Drug: Frexalimab; Pharmaceutical form:Solution for injection-Route of administration:IV; Other Names: SAR441344; Drug: Frexalimab; Pharmaceutical form:Solution for injection-Route of administration:SC; Other Names: SAR441344; Drug: rabbit anti-thymocyte globulin; Pharmaceutical form:Solution for injection-Route of administration:IV; Drug: mycophenolate mofetil; Pharmaceutical form:Tablet or capsule-Route of administration:Oral; Drug: mycophenolate sodium; Pharmaceutical form:Tablet-Route of administration:Oral; Drug: methylprednisolone; Pharmaceutical form:Solution for injection-Route of administration:IV; Drug: prednisone; Pharmaceutical form:Tablet-Route of administration:Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite efficacy failure rate (BPAR, graft loss, and death) by 1 year post kidney transplantation	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.	by 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
eGFR at 1 year post kidney transplantation	eGFR will be calculated with CKD-EPI 2021 formula, based on the creatinine value, age, and gender of the participant	at 1 year
eGFR at 6 months, 2 years, 3 years, 4 years, and 5 years post kidney transplantation	eGFR will be calculated with CKD-EPI 2021 formula, based on the creatinine value, age, and gender of the participant	at 6 months, 2 years, 3 years, 4 years, and 5 years
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	defined as protein concentration in the urine	at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years
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

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

Helpful Links

• EFC18554 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2026
• Primary Completion (Estimated): August 15, 2029
• Study Completion (Estimated): August 15, 2033

Study Registration Dates

• First Submitted: February 3, 2026
• First Submitted That Met QC Criteria: February 11, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Fatty Acids; Lipids; Acids, Acyclic; Carboxylic Acids; Polycyclic Compounds; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Macrolides; Lactones; Pregnadienetriols; Pregnadienediols; Biological Products; Complex Mixtures; Caproates; Prednisolone; Immune Sera; Prednisone; Mycophenolic Acid; Methylprednisolone; Tacrolimus; Antilymphocyte Serum
• Other Study ID Numbers: EFC18554; 2025-521521-33-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No