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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nantes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

10 Dec 2024 → ongoing

Decision date (initial)

2024-01-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Agence nationale de la recherche ( French National research agency )

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective 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

Secondary objectives 5

1. Show that patients in the ultra-minimization arm have a risk of immunological events and of graft loss comparable to those observed in the SOC arm
2. Show that patients in the ultra-minimization arm have a lower prevalence metabolic disorders
3. Show that patients in the ultra-minimization arm have a better adhere to the treatment
4. Show that patients in the ultra-minimization arm have a better quality of life
5. show that patient in the ultra minimization arm will have an improvement of the renal function

Conditions and MedDRA coding

kidney transplantation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Adult patient
2. Patients treated with Tacrolimus (Prograf® or Advagraf®) and MMF / MPS +/- Corticosteroid (CS)
3. First kidney transplantation
4. Living or a brain death or deceased donor (Maastricht 3)
5. Compatible for ABO group with the donor
6. One year post kidney transplantation ( between 350 et 515 days after the transplantation)
7. cPRA (ou TGI <20%) 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
8. Normal or IFTA 1-2 histology on one-year surveillance biopsy or within the month before the V1 visit
9. Patient insured under a health insurance scheme, according to national regulation.
10. Patient (of childbearing age) with effective contraception (sexual abstinence, use of a condom with spermicide, contraceptive sponge, uterine diaphragm, hormonal contraception, or intrauterine contraceptive device) The contraception should be used throughout the entire study period.
11. Eplet Mismatchs <= 14

Exclusion criteria 8

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the AGORAC Trial will be the improvement of the renal function (mGFR) at 18 months after “ultra” minimization of Tacrolimus (TAC: Prograf®, Advagraf®) as assessed by iohexol clearance3

Secondary endpoints 10

1. Compare between the two treatment arms at the end of the 18-month follow-up, the incidence of Biopsy proven rejection (BPAR) according to the 2017 Banff classification (including borderline lesions)31
2. Compare between the two treatment arms at the end of the 18-month follow-up the type, severity and treatment of BPAR
3. Compare between the two treatment arms at the end of the 18-month follow-up the Appearance of de novo DSA (4 digits and MFI threshold >500)
4. Compare between the two treatment arms at the end of the 18-month follow-up the appearance or worsening of histological lesions of interstitial fibrosis and inflammatory tubular atrophy (at indication biopsy or the end of the study) of study biopsy by considering that only patients with normal histology or with an IFTA-1 or 2 will be randomized
5. Compare between the two treatment arms at the end of the 18-month follow-up the prevalence of death, and graft loss at end of study
6. Compare between the two treatment arms at the end of the 18-month follow-up the Prevalence of metabolic disorders: post-transplant diabetes mellitus (PTDM), dyslipidaemia and hypertension at end of study
7. Compare between the two treatment arms at the end of the 18 months follow up the treatment adherence consisting in monitoring immunosuppression adherence using Trackyourmed® to monitor individual variability tacrolimus intake
8. Compare between the two treatment arms at the end of the 18 months follow up the change in quality of life estimated using the EQ-5D questionnaire fulfilled by patients at baseline, M3, M6, M9, M12, M15 and M18
9. Estimated Glomerular Filtartion rate (eGFR) will be calculated at 12 months by CKD-EPI
10. compared between the two treatment arms at the end of the 18-month follow-up: 9. Composite endpoint : incidence of either secondary endpoint #1 or #3 or #4 or #5 or #6.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nantes

Sponsor organisation

Centre Hospitalier Universitaire De Nantes

Address

5 Allee De L Ile Gloriette, Cs 69301 Cs 69301

City

Nantes Cedex 1

Postcode

44093

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Pr GIRAL

Public contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Pr GIRAL

Locations

3 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications