search
Back to results

Interferon Alfa Therapy Based on Th17 Profile in Membranous Nephropathy (ALPHAGEM)

Primary Purpose

Membranous Nephropathy

Status
Not yet recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Peginterferon Alfa-2A 180 MCG/ML Injectable Solution
Sponsored by
Centre Hospitalier Universitaire de Nice
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Membranous Nephropathy focused on measuring Membranous nephropathy, Immunomodulatory therapy, Interferon alpha, Interleukine 17-A (IL-17A), Personalized medicine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 Exclusion Criteria: 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

Sites / Locations

  • CHU de NICE

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

6-month interferon alfa treatment

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Nephrotic syndrome monitoring over 6-month interferon alfa treatment
Intra-individual variation in proteinuria (g/g) under IFN alfa and stable symptomatic treatment
Nephrotic syndrome monitoring over 6-month interferon alfa treatment
Intra-individual variation in albuminemia (g/L) under IFN alfa and stable symptomatic treatment
Immune response monitoring over 6-month interferon alfa treatment
Intra-individual variation in cytokine profile (assay of 8 cytokines in pg/ml: IL-12p70; IL-17A; IL-4; IL-5; IL-1β; IL-10; IFNα; IL-6) before and after 6 months of personalized treatment with IFN alfa
Immune response monitoring over 6-month interferon alfa treatment
Intra-individual variation in cytokine profile (assay of 1 cytokine in UI/ml: IFNγ) before and after 6 months of personalized treatment with IFN alfa
Clinical Tolerance monitoring over 6-month interferon alfa treatment
Percentage of Participants with clinical Adverse Events (AEs)
Biological Tolerance monitoring over 6-month interferon alfa treatment
Percentage of Participants with biological Adverse Events (AEs)

Full Information

First Posted
June 20, 2023
Last Updated
July 4, 2023
Sponsor
Centre Hospitalier Universitaire de Nice
search

1. Study Identification

Unique Protocol Identification Number
NCT05941845
Brief Title
Interferon Alfa Therapy Based on Th17 Profile in Membranous Nephropathy
Acronym
ALPHAGEM
Official Title
Study of Immunological Activity After Personalized Immunomodulatory Therapy Regulating the Th17 Pathway in Patients With Membranous Nephropathy
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 24, 2023 (Anticipated)
Primary Completion Date
January 24, 2025 (Anticipated)
Study Completion Date
July 24, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Nice

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
Membranous Nephropathy (MN) is a renal autoimmune disease mediated by autoantibodies, in particular the anti-phospholipase A2 receptor antibodies (anti-PLA2R1). The development of these autoantibodies is the consequence of a genetic predisposition, environmental factors and a dysregulation of the immune response, with increased production of pro-inflammatory Th2 and Th17 cytokines. Current management is based on the use of immunosuppressive therapies to induce immunological remission, which precedes clinical remission. Disease relapse may occur in 5-28% of patients, and may be complicated by long-term renal failure. MN patients with a pro-inflammatory Th17 cytokine profile have a 10.5-fold increased risk of disease relapse. Rituximab induces the regulatory T pathway, but has no impact on the Th17 pathway. 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. These treatments have been used for many years in the management of autoimmune diseases (such as multiple sclerosis for interferon beta) and viral infectious diseases (such as chronic hepatitis B for interferon alfa), affections where the Th17 pathway plays a key pathophysiological role. 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 with immunological relapse and a Th17-type cytokine profile, and to assess drug tolerance.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Membranous Nephropathy
Keywords
Membranous nephropathy, Immunomodulatory therapy, Interferon alpha, Interleukine 17-A (IL-17A), Personalized medicine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
6-month interferon alfa treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Peginterferon Alfa-2A 180 MCG/ML Injectable Solution
Other Intervention Name(s)
Pegasys®, interferon alfa
Intervention Description
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).
Primary Outcome Measure Information:
Title
Membranous nephropathy immunological activity monitoring over 6-month interferon alfa treatment
Description
Intra-individual variation in anti-PLA2R1 antibody titer (ELISA titer in RU/mL), before and after 6 months of treatment with IFN alfa
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Nephrotic syndrome monitoring over 6-month interferon alfa treatment
Description
Intra-individual variation in proteinuria (g/g) under IFN alfa and stable symptomatic treatment
Time Frame
Baseline to Week 24
Title
Nephrotic syndrome monitoring over 6-month interferon alfa treatment
Description
Intra-individual variation in albuminemia (g/L) under IFN alfa and stable symptomatic treatment
Time Frame
Baseline to Week 24
Title
Immune response monitoring over 6-month interferon alfa treatment
Description
Intra-individual variation in cytokine profile (assay of 8 cytokines in pg/ml: IL-12p70; IL-17A; IL-4; IL-5; IL-1β; IL-10; IFNα; IL-6) before and after 6 months of personalized treatment with IFN alfa
Time Frame
Baseline to Week 24
Title
Immune response monitoring over 6-month interferon alfa treatment
Description
Intra-individual variation in cytokine profile (assay of 1 cytokine in UI/ml: IFNγ) before and after 6 months of personalized treatment with IFN alfa
Time Frame
Baseline to Week 24
Title
Clinical Tolerance monitoring over 6-month interferon alfa treatment
Description
Percentage of Participants with clinical Adverse Events (AEs)
Time Frame
At Week 52
Title
Biological Tolerance monitoring over 6-month interferon alfa treatment
Description
Percentage of Participants with biological Adverse Events (AEs)
Time Frame
At Week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maxime TEISSEYRE, MD
Phone
+33492038828
Email
teisseyre.m@chu-nice.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Céline FERNANDEZ, MsC
Phone
+33492038828
Email
fernandez.c3@chu-nice.fr
Facility Information:
Facility Name
CHU de NICE
City
Nice
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Céline FERNANDEZ
Phone
+33492038828
Email
fernandez.c3@chu-nice.fr

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Not planed

Learn more about this trial

Interferon Alfa Therapy Based on Th17 Profile in Membranous Nephropathy

We'll reach out to this number within 24 hrs