Tacrolimus Minimization in Kidney Transplant Recipients Selected According to the AGORA Algorithm for Their Low Immunological Risk and Medium-term Graft Failure (AGORAC)

Prospective, Multicenter, Randomized, Open-label, Parallel-group Controlled Phase 3 Study of Tacrolimus Minimization in Kidney Transplant Recipients Selected According to the AGORA Algorithm for Their Low Immunological Risk and Medium-term Graft Failure

The goal of this clinical trial is that validation of the non-invasive biomarkers of the AGORA algorithm should make it possible to select patients with a very low immunological risk of graft failure to authorize safe minimization of their immunosuppression for adult patients at one-year post kidney transplantation.

The main question of the AGORAC trial is to demonstrate the impact of TACROLIMUS minimization using AGORA algorithm compared to standard of care on the kidney function 18 months after the minimization period.

Study Overview

• Status: Recruiting
• Conditions: Organ Grafts
• Intervention / Treatment: Drug: TACROLIMUS

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Magali GIRAL; Phone Number: +33240087443; Email: magali.giral@chu-nantes.fr
• Study Contact Backup: Name: Sonia Brinet; Phone Number: +33253526126

Study Locations

• France
  • Nantes, France, 44000
    • Recruiting
    • CHU de Nantes
    • Contact: Magali GIRAL
• Norway
  • Oslo, Norway
    • Not yet recruiting
    • Oslo University Hospital
    • Contact: Kristian Heldal
• Spain
  • Barcelona, Spain
    • Not yet recruiting
    • Hospital Universitari Vall d'Hebron
    • Contact: Oriol BESTARD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• First kidney transplantation
• Living or brain death or
• Donation after circulatory death (Maastricht 3) donor,Compatible for ABO group with the donor,
• cPRA (Panel Reactive Antibody Calculated ) (or TGI: Incompatible Graft Rate )<20% on the day of the transplantation and no DSA (MFI <500) at pre transplant and at the time of the inclusion at one-year post transplantation (between 350 and 515 days after the transplantation.
• Eplet Mismatchs <= 14
• Normal or IFTA 1-2 histology on one-year surveillance biopsy.
• Patient insured under a health insurance scheme, according to national regulation.
• Patient (of childbearing age) with effective contraception.
• Patients treated with Tacrolimus (Prograf® or Advagraf®) and MMF / MPS (Mycophenolate Sodium) +/- Corticosteroid (CS)

Exclusion Criteria:

• Donation after circulatory death maastricht 2 (uncontrolled) and maastricht 1
• Pregnant women (serum or urine test), breastfeeding women
• Patient under legal protection (incl. under guardianship or trusteeship)
• Participation to a drug interventional study within 1 month prior to the inclusion
• Any retransplantation and combined transplantations and also other organ previous transplantations
• History of lymphoproliferative disorders
• Diagnosis of a malignant disease (according to the type of malignancy)
• Hepatitis C antibody or hepatitis B surface antigen (HbsAg) positive patient or HIV infection

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
Experimental: Ultra-low TACROLIMUS arm; Ultra-low TACROLIMUS (TAC) arm based on MMF/MPA (Mycophenolate Mofetil/ Mycophénolic Acid) with or without CS (Cortico Steroid ) and TACROLIMUS to achieve 2-3.5 ng/ml trough levels during all the duration of the study.	Drug: TACROLIMUS; TACROLIMUS 2-3.5 ng/ml
No Intervention: SOC ( Standard of care)-TACROLIMUS arm; SOC-TAC arm based on MMF/MPA with or without CS and TACROLIMUS to achieve 4 and 7 ng/ml trough levels during all the duration of the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of the renal function at 18 months after "ultra" minimization of Tacrolimus	Improvement will be assessed by measured glomerular filtration rate (mGFR) iohexol clearance.	Month 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of biopsy-proven acute rejection (BPAR) according to the 2017 Banff classification (including borderline lesions)		Month 18
Type, severity and treatment of biopsy-proven acute rejection ( BPAR)		Month 18
Appearance of de novo donor-specific alloantibody (DSA) (4 digits and MFI treshold >500)		Month 18
Appearance or worsening of histological lesions of interstitial fibrosis and inflammatory tubular atrophy (IFTA) of study biopsy by considering that only patients with normal histology or with an IFTA-1 or 2will be randomized		Month 18
Prevalence of death, and graft loss (dialysis start or retransplantation) at end of study		Month 18
Prevalence of metabolic disorders: post-transplant diabetes mellitus (PTDM), dyslipidaemia and hypertension at end of study		Month 18
Treatment adherence consisting in monitoring immunosuppression adherence using Trackyourmed® to monitor individual variability tacrolimus intake		Month 18
Change in quality of life estimated using the EQ-5D ( EuroQol instrument - dimensions) questionnaire fulfilled by patients at baseline, Month 3, Month 6, Month 9, Month 12, Month15 and Month18	There is two score in the EQ-5D-5L The first one is the descriptive system: Minimum value:5 ( no problems on any dimension) Maximum value: 25 ( extreme problems on all dimensions) The second score is EQ VAS (EuroQol vertical visual analogue scale) score. It is rated on a scale of 0-100 points. 0 points correspond to the worst possible health status, while 100 points correspond to the best possible health status.	Month 3, Month 6, Month 9, Month 12, Month15 and Month18

Collaborators and Investigators

• Sponsor: Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2024
• Primary Completion (Estimated): June 10, 2028
• Study Completion (Estimated): December 10, 2028

Study Registration Dates

• First Submitted: January 23, 2024
• First Submitted That Met QC Criteria: January 23, 2024
• First Posted (Actual): February 1, 2024

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: kidney transplant; Tacrolimus minimization; AGORA Algorithm
• Additional Relevant MeSH Terms: Organic Chemicals; Macrolides; Lactones; Tacrolimus
• Other Study ID Numbers: RC22_0525

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No