ODORAT : Optimal dose of anti-lymphocyte globulin in kidney transplant recipients with low immunological risk

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional Universitaire

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

24 Jun 2025 → ongoing

Decision date (initial)

2024-10-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

CHU de Besançon · Neovii Pharmaceuticals AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response

The purpose of this study is to find the optimal non-depleting dose (MTD) of rabbit anti-human T-lymphocyte immunoglobulin (Grafalon®) to prevent the complications associated with prolonged CD4 T cell lymphopenia in low immunological risk renal transplant recipients.

Secondary objectives 8

1. To evaluate the tolerance of Grafalon® in each dose level
2. to evaluate the pharmacokinetic of Grafalon® during the treatment period and until month-3 in each dose level, to describe immune profile and immune restauration in each dose level
3. to describe time to event clinical endpoints since transplantation at each dose level
4. to describe the rate of patients with infection up to 1 year after transplantation in each dose level
5. to describe the number of infections by patients up to 1 year after transplantation in each dose level
6. to describe the rate of patients with an atherosclerotic event up to 1 year after transplantation in each dose level
7. to describe the rate of patients with a diagnosis of cancer up to 1 year after transplantation in each dose level
8. to describe Renal function at 1 year post transplant in each dose level

Conditions and MedDRA coding

renal transplant

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Age ≥ 18 years
2. Patient receiving first kidney transplantation

Exclusion criteria 8

1. History of opportunistic infection that required intensive care hospitalization in the two years preceding the transplant
2. Anti-HLA immunization (Flow PRA > or = 20%, presence of donor specific antibody before and/or at time of transplantation and with a positive CDC and FXM with historical and/or transplant day sera)
3. Multi-organ transplant
4. Previous transplant(s)
5. History of cancer
6. Thrombocytopenia < 50 000 platelets
7. Any active infections or Infection with Hepatitis C, B viruses or HIV
8. Pregnant or breast-feeding subjects,

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome for the de-escalation study is the DLT defined by a T cell (CD3+) relative depletion above 30 % compared to baseline (Day 0) at the end of the Grafalon® induction treatment (Day 4).

Secondary endpoints 8

1. Toxicities: Incidence and grade for Adverse events (AEs), drug related AEs, drug related AE leading to dose reduction or discontinuation during treatment, SAE and SUSAR, according to CTCAE V5.0.
2. Pharmacokinetic study including for each dose level the calculation of the plasmatic clearance evaluated by the AUC of Grafalon® at day 0 and day 4 and the trough level of Grafalon® at each visit until month-3.
3. The absolute count and proportion of different T and B cell subpopulations, NK cells, monocytes and neutrophils at each time point.
4. Time to Transplant failure defined as the time since transplantation to either graft loss or death with a functioning graft. Return to dialysis or retransplantation defined graft loss. Overall survival defined as the time since transplantation to death. Time to kidney allograft acute rejection defined as the time since transplantation since to kidney allograft acute rejection.
5. The infection up to 1 year after transplantation defined by : -the onset of a severe bacterial infection: all bacterial infections leading to patient hospitalization) -or an opportunistic infection: all types of infections that occur only in patients with an immune system deficiency and never in healthy patients (i.e. pneumocystis, tuberculosis, cryptococcosis, candidosis, Kaposi sarcoma, herpesviridae infections, B EBV lymphoma, HTLV T leukemia, toxoplasmosis, cryptococosis, polyomavirus vir
6. The atherosclerotic event up to 1 year after transplantation defined by major adverse cardiovascular events (MACE)
7. The diagnosis of cancer up to 1 year after transplantation defined by all types and stages of post transplant solid organ, cutaneous or hematological malignancies
8. Renal function at 1 year post transplant evaluated by estimated glomerular filtration rate (eGFR) calculated by the creatinine clearance according to the formula CKD-EPI : eDFG = 141 x min(Scr/k, 1)α x max(Scr/k, 1)-1.209 x 0.993âge x 1.018 [if female] x 1.159 [if African ethnicity]

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Universitaire

Sponsor organisation

Centre Hospitalier Regional Universitaire

Address

2 Place Saint Jacques, Cs 51804 Cs 51804

City

Besancon Cedex

Postcode

25030

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Universitaire

Contact name

Emilie GAIFFE

Public contact point

Organisation

Centre Hospitalier Regional Universitaire

Contact name

Ingrid TISSOT

Locations

1 EU/EEA country · 1 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 10 files

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

Application history

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