Comparison of the effects of Belatacept and Anticalcineurins on endothelial function in kidney transplant patients - BELAFENDO

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Rouen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Phenomena and Processes [G] - Biological Phenomena [G16], Phenomena and Processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

Trial duration

24 Jul 2025 → ongoing

Decision date (initial)

2024-10-01

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To demonstrate that replacing anticalcineurins with Belatacept in kidney transplant patients results in a 6-month improvement in endothelium-dependent dilation of peripheral conductance arteries in response to postischemic hyperemia compared to kidney transplant patients maintaining anticalcineurin therapy.

Secondary objectives 4

1. To demonstrate that replacing anticalcineurins with Belatacept in kidney transplant patients results in an improvement at 6 months in endothelium-dependent dilation of peripheral conductance arteries during a sustained increase in blood flow.
2. To demonstrate that replacing anticineurins with Belatacept allows a reduction in the stiffness of the aorta and its main branches after 6 months.
3. To demonstrate that replacing anticineurins with Belatacept allows a reduction in peripheral and central arterial pressures at 6 months.
4. To demonstrate that replacing anticineurins with Belatacept increases endothelial release of NO and EETs at 6 months in peripheral conductance arteries during sustained increases in blood flow.

Conditions and MedDRA coding

Kidney transplant

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. For the Belatacept group: - Patients who underwent a graft biopsy due to impaired renal function, finding criteria for chronic toxicity of anticalcineurins leading to the introduction of Belatacept.
2. For the anticalcineurin group: -Kidney transplant patients treated with anticalcineurin for more than one year.
3. For the anticalcineurin group: -Stable renal function (defined by a creatinine level in µmol/l stable for 3 months (variation +/-20%)
4. For both groups: Date of kidney transplant greater than 1 year
5. For both groups: Age between 18 and 75 years inclusive
6. For both groups: - Patient having received clear information from one of the investigators, having read and understood the information letter and signed the consent form
7. For both groups: - Women: o of childbearing age (defined by the CTCG as a fertile woman, after menarche and until menopause, except in cases of permanent sterility (including hysterectomy, bilateral salpingectomy or bilateral oophorectomy) • using effective contraception according to the CTCG (progestin-only oral hormonal contraception for which inhibition of ovulation is not the primary mode of action, male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide) for at least 4 weeks before inclusion, during the study and up to 8 weeks after the last dose of treatment And, - Having a negative urine pregnancy test at inclusion;
8. For both groups: - women: o Postmenopausal: Menopause according to CTCG is defined as the absence of menstruation for 12 months without other medical cause. A high level of follicle-stimulating hormone (FSH) in the postmenopausal interval can be used to confirm a postmenopausal state in women who are not using hormonal contraception or hormone replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
9. For both groups: - Patient benefiting from a social protection scheme

Exclusion criteria 17

1. Chronic kidney disease stage 5 (defined by a CKD-EPI GFR <15 ml/min/1.73m²)
2. Previous or current treatment with Belatacept
3. Severe hypertension (BP ≥ 110 mm Hg and/or SBP ≥ 180 mm Hg)
4. Presence or history of functional or ligated bilateral arteriovenous fistula or bilateral thrombosis, preventing vascular explorations
5. Pregnant or breastfeeding woman, or lack of proven effective contraception
6. Excessive alcohol consumption (no more than 10 drinks per week)
7. Dialysis patient
8. History of myocardial infarction or stroke less than 6 months ago
9. Systolic heart failure requiring hospitalization within 6 months prior to inclusion or known heart failure with an LVEF <30%
10. BMI>35 kg/m²
11. Severe hepatic impairment (Child-Pugh class C)
12. Contraindication to NULOJIX 250 mg, powder for solution for infusion
13. Contraindication to NATISPRAY 0.30 mg/dose, oral spray solution (and in particular hypersensitivity to nitrate derivatives in accordance with the SPC (Summary of Product Characteristics) of NATISPRAY)
14. Person deprived of liberty by an administrative or judicial decision or person placed under judicial protection, or guardianship or curatorship
15. Active smoking with a daily consumption of more than 21 mg of nicotine per day or taking nicotine substitutes with a dose greater than 21 mg/24 hours
16. Drug addiction or suspected illicit drug use
17. Patient participating or having participated in the 4 weeks preceding their inclusion in a clinical trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is to compare the 6-month change in the amplitude of endothelium-dependent dilation during the post-ischemic hyperemia maneuver (Section 7.1) (visit V2 and V3) measured by vascular ultrasound with automated real-time software analysis between the Belatacept group and the ancalcineurin group.

Secondary endpoints 4

1. To compare the 6-month variation in the amplitude of endothelium-dependent dilation during distal skin heating (Section 6.1) (visits V2 and V3) measured by echotraking (Section 6.1) between the Belatacept group and the anticalcineurin group.
2. Compare the 6-month variation in distensibility and Young's elastic modulus, indicators of carotid stiffness, will be measured 2 cm below the bifurcation by echotracking (Section 6.1)(visits V2 and V3) between the Belatacept group and the anticalcineurin group. And the 6-month variation in carotid-femoral PWV, an indicator of aortic stiffness, will be measured by applanation tonometry (Section 6.1)(visits V2 and V3) between the Belatacept group and the anticalcineurin group.
3. To compare the 6-month change in brachial and carotid arterial pressure measurements and in the carotid augmentation index, an indicator of cardio-circulatory coupling, measured by applanation tonometry (Section 6.1) (visits V2 and V3) between the Belatacept group and the anticalcineurin group. The augmentation index is calculated as the difference between the systolic peak and the inflection in protosystole, expressed as a percentage of the central pulse pressure.
4. To compare the 6-month variation in blood concentrations of nitrites and epoxyeicosatrienoic acids (EETs) (Section 6.1), an indicator of NO availability between 44°C and 34°C (visits V2 and V3) between the Belatacept group and the anticalcineurin group.

Investigational products

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

Test 1

Comparator 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Rouen

Sponsor organisation

Centre Hospitalier Universitaire Rouen

Address

1 Rue De Germont, Bp 96031 Bp 96031

City

Rouen Cedex

Postcode

76031

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

Nell Marty

Public contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

Nell Marty

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 12 files

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

Application history

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