Interferon Alfa Therapy Based on Th17 Profile in Membranous Nephropathy

NCT05941845 | Terminated Phase 2

• 1 other identifier: 22-AOIP-03
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Membranous Nephropathy (MN) is a renal autoimmune disease mediated by autoantibodies. Current management is based on the use of immunosuppressive therapies. MN patients with a pro-inflammatory Th17 cytokine profile have a 10.5-fold increased risk of disease relapse. Interferon-based immunomodulatory therapies are effective in blocking the production of cytokines in the Th17 pathway avoiding an increased risk of infection, unlike immunosuppressive treatments. To date, these treatments have not been evaluated in the management of MN. The aims of the ALPHAGEM project are to monitor the immunological activity of the disease before and after 6 months of personalized interferon-alfa treatment in MN patients.

Conditions

Membranous Nephropathy

Keywords

Membranous nephropathy; Immunomodulatory therapy; Interferon alpha; Interleukine 17-A (IL-17A); Personalized medicine

Outcome Measures

Primary Outcomes (1)

• Membranous nephropathy immunological activity monitoring over 6-month interferon alfa treatment

  Intra-individual variation in anti-PLA2R1 antibody titer (ELISA titer in RU/mL), before and after 6 months of treatment with IFN alfa

  18 months

Secondary Outcomes (6)

• Nephrotic syndrome monitoring over 6-month interferon alfa treatment

  Baseline to Week 24

• Nephrotic syndrome monitoring over 6-month interferon alfa treatment

  Baseline to Week 24

• Immune response monitoring over 6-month interferon alfa treatment

  Baseline to Week 24

• Immune response monitoring over 6-month interferon alfa treatment

  Baseline to Week 24

• Clinical Tolerance monitoring over 6-month interferon alfa treatment

  At Week 52

Study Arms (1)

6-month interferon alfa treatment

EXPERIMENTAL

Drug: Peginterferon Alfa-2A 180 MCG/ML Injectable Solution

Interventions

Peginterferon Alfa-2A 180 MCG/ML Injectable Solution DRUG

Injections will be carried out on the Nephrology day hospitalization ward. The injections follows a personalized administration schedule: all enrolled patients will receive an injection of Pegasys® at Week 0. Patients with a persistent Th17 profile (cytokine profile showing IL-17A levels greater than 73 pg/ml) at Week 2 will receive a new dose of Pegasys®, followed by a monthly cytokine profile. In the case of a persistent Th17 profile, 2 injections will be given two weeks apart. In patients with no Th17 profile at Week 2, no Pegasys® injections will be performed at this time. Cytokine profiles will be performed monthly, and in the case of a persistent Th17 profile, 1 injection will be performed. In total, patients will receive a minimum of one injection and a maximum of 13 injections of 180 µg (1 injection every two weeks for 24 weeks).

Also known as: Pegasys®, interferon alfa

6-month interferon alfa treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 and above
• Diagnosis of membranous nephropathy PLA2R1 antibodies-mediated
• Immunological relapse (defined as an increase in anti-PLA2R1 antibody titer \> 14 RU/mL after a phase of anti-PLA2R1 antibody negativation, i.e. immunological remission)
• Plasma IL-17A levels \> 73 pg/mL after non-specific stimulation of peripheral blood immune cells
• Symptomatic anti-proteinuric treatment at a stable, maximum-tolerated dosage;
• Patients 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) at screening

You may not qualify if:

• Immunosuppressive treatment for MN in the 6 months before screening
• Secondary MN (associated with cancer, infectious disease, autoimmune or iatrogenic disease)
• Active nephrotic syndrome defined according to KDIGO guidelines by proteinuria \> 3.5 g/day (or 3.5 g/g urine sample) and albuminemia \< 30 g/L
• Absence of previous immunological (anti-PLA2R1 antibodies \< 14 RU/mL in ELISA or negative indirect immunofluorescence) and clinical (partial or complete) remission
• Patients with a history of thrombosis or treated with anticoagulants
• Pregnancy or breastfeeding
• Cancer in treatment
• Pre-existing retinopathy
• Active and severe infections
• Severe liver failure or cirrhosis
• Pre-existing severe heart failure
• Pre-existing psychiatric disorder or patient at risk of anxiety or depression (HAD Score \> 11)
• Patients who use or abuse substances
• Hypersensitivity to active substance or excipients of study treatment

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (1)

CHU de NICE

Nice, France

Location

MeSH Terms

Conditions

Glomerulonephritis, Membranous

Interventions

peginterferon alfa-2a; Interferon-alpha

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: July 12, 2023
• Study Start: September 14, 2023
• Primary Completion: September 14, 2025
• Study Completion: September 14, 2025
• Last Updated: June 18, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)