Efficiency of everolimus for the treatment of kidney transplanted patients presenting a rejection

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospices Civils De Lyon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

3 Dec 2020 → ongoing

Decision date (initial)

2024-09-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

French Ministry of Health

External identifiers

EU CT number

2024-513814-37-00

EudraCT number

2019-001849-41

ClinicalTrials.gov

NCT03955172

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the effectiveness of everolimus in preventing deterioration of graft function at 6 months in adult kidney transplant patients with NK-mediated rejection

Secondary objectives 3

1. - Evaluate the impact of everolimus on the severity of histological lesions at 6 months in adult kidney transplant patients with NK-mediated rejection.
2. - Evaluate the impact of everolimus on the degree of NK activability at 6 months in adult kidney transplant patients with NK-mediated rejection.
3. - Evaluate the impact of everolimus in limiting the occurrence of proteinuria, a marker of chronic glomerular damage in adult kidney transplant patients with NK-mediated rejection.

Conditions and MedDRA coding

Renal Transplantation

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Major renal transplant patient
2. Patient who had a renal graft biopsy as part of the usual follow-up finding microvascular inflammatory lesions (glomerulitis + peritubular capillaritis ≥ 2) associated with moderate chronic lesions (cg < 3 and cv < 3) according to the Banff classification 2013
3. Having a predictable “missing self”: patient having a mismatch between the HLA class I ligands of inhibitory KIRs present in the recipient and the ligands present in the recipient
4. Patient receiving at least dual immunosuppressive therapy including: an anticalcineurin (tacrolimus or cyclosporine), an antimetabolite (mycophenolic acid (CELLCEPT or MYFORTIC) or azathioprine (IMUREL)).
5. Taking effective contraception for up to 8 weeks after the end of treatment with everolimus (CERTICAN)
6. Patient affiliated to a social insurance regimen
7. An absence of anti-endothelial cell antibodies in their serum tested for by an endothelial cross match
8. At least 1 confirmed missing self: the recipient has at least one functional KIR inhibitor present genotypically whose HLA class I ligand is not present in the donor

Exclusion criteria 11

1. - Patients at high immunological risk: presence of preformed specific anti-HLA antibodies or hyperimmunized patients (incompatible graft rate > 85%) on the day of the transplant.
2. - Proteinuria > 1 g/day (or 100 mg/mmol creatininuria)
3. - History of poor tolerance of everolimus
4. Hypersensitivity to everolimus, sirolimus or one of its excipients as mentioned in the SPC of everolimus paragraph 4.3 and 6.1.
5. - Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome
6. Surgery planned for the next 6 months
7. - Severe chronic lesions (cg > 2 or cv > 2) according to the Banff 2013 classification on the classic histological examination of a graft biopsy
8. - Presence of donor-specific anti-HLA antibodies in their serum on the day of the biopsy searched by Luminex
9. Positive endothelial cross match with serum from the day of the biopsy
10. - Subject participating in another research including an exclusion period still in progress at pre-inclusion
11. Pregnant, breastfeeding women, minors, adults under guardianship or curatorship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Relative variation in Glomerular Filtration Rate (GFR) estimated by the CKD-EPI method between D-15 and M6 after starting everolimus.

Secondary endpoints 3

1. Histological: variation in the microvascular inflammation score (g+cpt) and chronic glomerular (cg) and vascular (cv) lesions determined according to the Banff 2013 classification between D-15 and M6
2. Biological: variation in the degree of in vitro activability of NK between D0 and M6
3. Clinical: relative variation in the proteinuria/creatininuria ratio between D-15 and M6

Investigational products

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

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospices Civils De Lyon

Sponsor organisation

Hospices Civils De Lyon

Address

3 Quai Des Celestins, Bp 2251 Bp 2251

City

Lyon Cedex 02

Postcode

69229

Country

France

Scientific contact point

Organisation

Hospices Civils De Lyon

Contact name

Dr Koenig

Public contact point

Organisation

Hospices Civils De Lyon

Contact name

Dr Koenig

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 14 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