Study of immunological activity after personalized immunomodulatory therapy regulating the Th17 pathway in patients with extramembranous glomerulonephritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nice

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

18 Jul 2023 → 14 Sep 2025

Decision date (initial)

2023-06-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

CHU de Nice

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety

To measure the immunological activity of GEM with anti-PLA2R1 antibodies in immunologically relapsed patients with a Th17-like cytokine profile before and after 6 months of personalized IFNα (Pegasys®) therapy.

Secondary objectives 4

1. To measure the occurrence of clinical relapse in immunologically relapsed GEM patients with anti-PLA2R1 antibodies and a Th17-like cytokine profile during the study
2. To measure cytokine production of Th17, Th2, Th1 and Treg pathways in GEM patients with immunologically relapsed anti-PLA2R1 antibodies and a Th17-like cytokine profile before and after 6 months of personalized IFNα (Pegasys®) therapy
3. To Evaluate the tolerability of IFNα (Pegasys®) in GEM patients with immunologically relapsed anti-PLA2R1 antibodies and a Th17 cytokine profil
4. To compare IFNα (Pegasys®) regimens received in GEM patients with immunologically relapsed anti-PLA2R1 antibodies based on their Th17 cytokine profile

Conditions and MedDRA coding

Extramembranous glomerulonephritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Subjects 18 years or older
2. GEM with anti-PLA2R1 autoantibody
3. Immunological relapse (defined by an increase in anti-PLA2R1 antibody titre > 14 RU/mL after a negative phase of anti-PLA2R1 antibodies, that is, immunological remission)
4. IL-17A plasma levels > 73 pg/mL after non-specific stimulation of peripheral blood immune cells
5. Symptomatic antiprotein treatment with stable and maximum tolerated dosage
6. Patients with a biological workup at the screening visit with (i) a platelet count≥ 90,000 cells/mm3; (ii) a neutrophil count ≥ 1500 cells/mm3; and (iii) appropriately monitored normal thyroid function (TSH and T4)

Exclusion criteria 14

1. Immunosuppressive treatment for GEM within 6 months prior to the screening visit
2. Pre-existing severe heart failure
3. Pre-existing psychiatric disorder or patient likely to be anxious or depressed (HAD score > 11)
4. Patients using substances or abusing substances
5. Hypersensitivity to the active substance or excipients of the study treatment
6. Secondary GEM (associated with cancer, infectious disease, autoimmune or iatrogenic disease)
7. Active nephrotic syndrome defined by KDIGO guidelines as proteinuria > 3.5 g/day (or 3.5 g/g on urine sample) and albumin < 30 g/L
8. Absence of immunological (anti-PLA2R1 antibody < 14 RU/mL in ELISA or negative indirect immunofluorescence) and clinical (partial or complete) remission
9. Patients with a history of thrombosis or on anticoagulant therapy
10. Cancer under treatment
11. Pre-existing retinopathies
12. Active and severe infections
13. Severe liver failure or cirrhosis
14. Pregnancy or breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Intraindividual variation in anti-PLA2R1 antibody titer (ELISA titer in RU/mL), after 6 months of IFNα (Pegasys®) treatment compared to pre-treatment antibody titer

Secondary endpoints 4

1. Intraindividual variation in proteinuria and albumin levels under IFNα (Pegasys®) treatment and stable symptomatic treatment
2. Intraindividual variation in cytokine profile (assay of 9 cytokines: IL-12p70; IL-17A; IL-4; IL-5; IL-1β; IL-10; IFNα; IL-6 and IFNγ) before and after 6 months of personalized treatment with IFNα (Pegasys®)
3. Clinical and Biological Tolerance of IFNα Therapy (Pegasys®)
4. Description of an effective IFNα (Pegasys®) regimen (one or two monthly doses) to induce an IL-17A level below 73 pg/ml

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nice

Sponsor organisation

Centre Hospitalier Universitaire De Nice

Address

4 Avenue Reine Victoria

City

Nice

Postcode

06000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nice

Contact name

TEISSEYRE Maxime

Public contact point

Organisation

Centre Hospitalier Universitaire De Nice

Contact name

FERNANDEZ Céline

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

Application history

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