Membranous NephropathyPhase 2ALPHAGEMNCT05941845
Interferon Alfa Therapy Based on Th17 Profile in Membranous Nephropathy
A Phase 2 study testing Peginterferon Alfa-2A 180 MCG/ML Injectable Solution in people with Membranous Nephropathy, run by Centre Hospitalier Universitaire de Nice at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Membranous Nephropathy
- What is being tested?
- Peginterferon Alfa-2A 180 MCG/ML Injectable Solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteFrance
- Study dates
- 14 Sep 2023to 14 Sep 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study of Immunological Activity After Personalized Immunomodulatory Therapy Regulating the Th17 Pathway in Patients With Membranous Nephropathy
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.
Read the 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.
- Conditions
- Membranous Nephropathy
- Being tested
- Peginterferon Alfa-2A 180 MCG/ML Injectable Solution
- Keywords
- Membranous nephropathy, Immunomodulatory therapy, Interferon alpha, Interleukine 17-A (IL-17A), Personalized medicine
- Medical subject headings
- Glomerulonephritis, Membranous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Peginterferon Alfa-2A 180 MCG/ML Injectable SolutionDrug
Also called Pegasys®, interferon alfa
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).
| Study group | Role | What they receive |
|---|---|---|
| 6-month interferon alfa treatment | Experimental | Not described Receives: Drug: Peginterferon Alfa-2A 180 MCG/ML Injectable Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 18 months
Secondary outcomes (6)
Nephrotic syndrome monitoring over 6-month interferon alfa treatment
Intra-individual variation in proteinuria (g/g) under IFN alfa and stable symptomatic treatment
Measured: Baseline to Week 24
Nephrotic syndrome monitoring over 6-month interferon alfa treatment
Intra-individual variation in albuminemia (g/L) under IFN alfa and stable symptomatic treatment
Measured: Baseline to Week 24
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
Measured: Baseline to Week 24
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
Measured: Baseline to Week 24
Clinical Tolerance monitoring over 6-month interferon alfa treatment
Percentage of Participants with clinical Adverse Events (AEs)
Measured: At Week 52
Biological Tolerance monitoring over 6-month interferon alfa treatment
Percentage of Participants with biological Adverse Events (AEs)
Measured: At Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2023
- Study start14 Sep 2023
- Primary completion14 Sep 2025
- Study completion14 Sep 2025
Why it stopped: Only screenfail during inclusion period
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Membranous NephropathyStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NiceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05941845
- Sponsor's protocol ID
- 22-AOIP-03
- Acronym
- ALPHAGEM
- Status last verified
- Jun 2026
- First submitted
- 20 Jun 2023
- Last updated
- 18 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Not planed
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Immunological Activity After Personalized Immunomodulatory Therapy Regulating the Th17 Pathway in Patients With Membranous Nephropathy
- ClinicalTrials.gov ID
- NCT05941845
- Acronym / sponsor ID
- ALPHAGEM / 22-AOIP-03
- Conditions
- Membranous Nephropathy
- Keywords
- Membranous nephropathy, Immunomodulatory therapy, Interferon alpha, Interleukine 17-A (IL-17A), Personalized medicine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Only screenfail during inclusion period
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- 14 Sep 2023 (actual)
- Primary completion
- 14 Sep 2025 (actual)
- Study completion
- 14 Sep 2025 (actual)
- First posted
- 12 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 6-month interferon alfa treatment | Experimental | Drug: Peginterferon Alfa-2A 180 MCG/ML Injectable Solution |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Peginterferon Alfa-2A 180 MCG/ML Injectable SolutionAlso: Pegasys®, interferon alfaInjections 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). | Drug | 6-month interferon alfa treatment |
Primary outcome
Membranous nephropathy immunological activity monitoring over 6-month interferon alfa treatment
Time frame: 18 months
Intra-individual variation in anti-PLA2R1 antibody titer (ELISA titer in RU/mL), before and after 6 months of treatment with IFN alfa
6 secondary outcomes
Nephrotic syndrome monitoring over 6-month interferon alfa treatment
Time frame: Baseline to Week 24
Nephrotic syndrome monitoring over 6-month interferon alfa treatment
Time frame: Baseline to Week 24
Immune response monitoring over 6-month interferon alfa treatment
Time frame: Baseline to Week 24
Immune response monitoring over 6-month interferon alfa treatment
Time frame: Baseline to Week 24
Clinical Tolerance monitoring over 6-month interferon alfa treatment
Time frame: At Week 52
Biological Tolerance monitoring over 6-month interferon alfa treatment
Time frame: At Week 52
Results and safety
The study was stopped early (reason given: Only screenfail during inclusion period). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2026.
- Individual participant dataSharing planned: No. Not planed
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Peginterferon Alfa-2A 180 MCG/ML Injectable Solution in people with Membranous Nephropathy, run by Centre Hospitalier Universitaire de Nice at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Only screenfail during inclusion period). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Membranous nephropathy immunological activity monitoring over 6-month interferon alfa treatment (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2026.