Myasthenia Gravis GeneralizedINFORMNCT06685055
Markers of Favorable Response to FcRn Inhibitors(INFORM)
An observational study of Myasthenia Gravis Generalized, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
Myasthenia gravis is an autoimmune neurological disease caused by autoantibodies primarily directed against components of the postsynaptic membrane of the neuromuscular junction. Approximately 85% of patients have antibodies directed against the acetylcholine receptor (anti-AChR). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myasthenia Gravis Generalized
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- 9 Jul 2024to 9 Jul 2026
- Phase
- Observational
- 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
Study population: Patients with generalized Myasthenia Gravis positive for anti-AChR antibodies undergoing therapy with FcRn inhibitor drugs
Who may be able to join
- Age ≥18 years.
- Diagnosis of generalized anti-AChR positive Myasthenia Gravis.
- Need for therapy with neonatal Fc receptor inhibitors for immunoglobulins (FcRn) as per AIFA-approved therapeutic indications (14).
- Ability to follow up at the reference center.
- Signed informed consent for the study.
Who cannot join
- Age \<18 years.
- Poor compliance with drug therapy.
- Concurrent autoimmune diseases.
- Insufficient availability of clinical information.
- Ongoing neoplasm or infection at the time of biological sample collection.
- Refusal to sign the informed consent for the study.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Fondazione Policlinico Universitario A. Gemelli IRCCS
Rome, 00168
Raffaele Iorio, MD, PhD, +390630154807, raffaele.iorio@policlinicogemelli.it
Silvia Falso, MD, +390630154807, falsosilvia@gmail.com
About this study
Official title: Identification of Clinical, Biological, Cellular and Genetic Markers of Favorable Response to Therapy With Neonatal Fc Receptor Inhibitors for Immunoglobulins (FcRn) in Patients With Generalized Myasthenia Gravis (INFORM)
Myasthenia gravis is an autoimmune neurological disease caused by autoantibodies primarily directed against components of the postsynaptic membrane of the neuromuscular junction. Approximately 85% of patients have antibodies directed against the acetylcholine receptor (anti-AChR).
Anti-AChR antibodies act through three distinct mechanisms:
Read more
- Activation of the classical complement pathway: Formation of membrane-attack complexes (MACs) results in the destruction of the postsynaptic membrane.
- Mechanical blockade: Anti-AChR antibodies block the acetylcholine binding site on its receptor.
- Internalization and lysosomal degradation: Bivalent IgG causes cross-linking of adjacent receptors leading to internalization and degradation of AChRs (antigenic modulation).
Patient mortality has significantly reduced due to effective treatments preventing severe exacerbations of myasthenic symptoms.
In the past five years, the FDA and EMA have approved complement inhibitors and FcRn inhibitors for treating generalized myasthenia gravis with anti-AChR antibodies. Many other therapies are currently in phase 3 clinical trials or under regulatory review. However, there is no specific evidence to support which patients benefit most from one treatment class over another.
Given their relative efficacy compared to conventional therapies and high costs, their future role in the therapeutic arsenal is unclear. A personalized approach considering the different pathogenic mechanisms of anti-AChR and single gene polymorphisms involved in treatment response is essential for effective therapeutic choice. In July 2023, AIFA approved the reimbursement of Efgartigimod in Italy for treating adult patients with generalized myasthenia gravis with anti-AChR antibodies, in addition to standard therapy.
FcRn inhibitors (including Efgartigimod) prevent the interaction of IgG with the neonatal Fc receptor for immunoglobulin fragments, reducing IgG recycling and promoting the degradation of IgG and pathogenic antibodies without affecting albumin levels.
There is heterogeneity among patients in their response to FcRn inhibitors therapies. Currently, there is no specific evidence indicating which patients may benefit most from this class of treatments. Interindividual heterogeneity in the autoantibody repertoire, predominance of different pathogenic mechanisms, and single gene polymorphisms affecting treatment response. Investigating the immune profile and specific gene polymorphisms in myasthenic patients needing these innovative therapies could identify predictive biomarkers and personalize therapeutic choices.
- Conditions
- Myasthenia Gravis Generalized
- Medical subject headings
- Myasthenia Gravis
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of Clinical Markers of Favorable Response to FcRn Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Analyze the clinical status of patients comparing the results of MG-ADL clinical scale pre/post FcRn Inhibitors
Measured: 24 months
Identification of Biological and Cellular Markers of Favorable Response to FcRn Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Analyze the differences between IgG levels pre/post therapy with FcRn inhibitors
Measured: 24 months
Identification of Biological and Cellular Markers of Favorable Response to FcRn Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
- Evaluate anti-AChR positivity in patients treated with FcRn inhibitors
Measured: 24 months
Identification of Biological and Cellular Markers of Favorable Response to FcRn Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
- Dosage of proteins involved in pathogenesis
Measured: 24 months
Identification of Genetic Markers of Favorable Response to FcRn Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Investigate the presence of polymorphisms in the FCGRT gene (VTNRs) in patients refractory to therapy with FcRn inhibitors
Measured: 24 months
Identification of Clinical Markers of Favorable Response to FcRn Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Analyze the clinical status of patients comparing the results of QMG clinical scale pre/post FcRn Inhibitors
Measured: 24 months
Secondary outcomes (1)
Predictive algorithm of favorable response
Create a predictive algorithm for response to FcRn inhibitor therapies by combining clinical, cellular, biological, and genetic parameters
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2024
- Study start9 Jul 2024
- Primary completion9 Jul 2026 (estimated)
- Study completion9 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myasthenia Gravis GeneralizedStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Raffaele Iorio, Principal investigator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06685055
- Sponsor's protocol ID
- 6717
- Acronym
- INFORM
- Status last verified
- Jul 2024
- First submitted
- 10 Jul 2024
- Last updated
- 12 Nov 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Clinical, Biological, Cellular and Genetic Markers of Favorable Response to Therapy With Neonatal Fc Receptor Inhibitors for Immunoglobulins (FcRn) in Patients With Generalized Myasthenia Gravis (INFORM)
- ClinicalTrials.gov ID
- NCT06685055
- Acronym / sponsor ID
- INFORM / 6717
- Conditions
- Myasthenia Gravis Generalized
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 9 Jul 2024 (actual)
- Primary completion
- 9 Jul 2026 (estimated)
- Study completion
- 9 Jul 2026 (estimated)
- First posted
- 12 Nov 2024 (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.
Myasthenia gravis is an autoimmune neurological disease caused by autoantibodies primarily directed against components of the postsynaptic membrane of the neuromuscular junction. Approximately 85% of patients have antibodies directed against the acetylcholine receptor (anti-AChR).
Anti-AChR antibodies act through three distinct mechanisms:
- Activation of the classical complement pathway: Formation of membrane-attack complexes (MACs) results in the destruction of the postsynaptic membrane.
- Mechanical blockade: Anti-AChR antibodies block the acetylcholine binding site on its receptor.
- Internalization and lysosomal degradation: Bivalent IgG causes cross-linking of adjacent receptors leading to internalization and degradation of AChRs (antigenic modulation).
Patient mortality has significantly reduced due to effective treatments preventing severe exacerbations of myasthenic symptoms.
In the past five years, the FDA and EMA have approved complement inhibitors and FcRn inhibitors for treating generalized myasthenia gravis with anti-AChR antibodies. Many other therapies are currently in phase 3 clinical trials or under regulatory review. However, there is no specific evidence to support which patients benefit most from one treatment class over another.
Given their relative efficacy compared to conventional therapies and high costs, their future role in the therapeutic arsenal is unclear. A personalized approach considering the different pathogenic mechanisms of anti-AChR and single gene polymorphisms involved in treatment response is essential for effective therapeutic choice. In July 2023, AIFA approved the reimbursement of Efgartigimod in Italy for treating adult patients with generalized myasthenia gravis with anti-AChR antibodies, in addition to standard therapy.
FcRn inhibitors (including Efgartigimod) prevent the interaction of IgG with the neonatal Fc receptor for immunoglobulin fragments, reducing IgG recycling and promoting the degradation of IgG and pathogenic antibodies without affecting albumin levels.
There is heterogeneity among patients in their response to FcRn inhibitors therapies. Currently, there is no specific evidence indicating which patients may benefit most from this class of treatments. Interindividual heterogeneity in the autoantibody repertoire, predominance of different pathogenic mechanisms, and single gene polymorphisms affecting treatment response. Investigating the immune profile and specific gene polymorphisms in myasthenic patients needing these innovative therapies could identify predictive biomarkers and personalize therapeutic choices.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with generalized Myasthenia Gravis positive for anti-AChR antibodies undergoing therapy with FcRn inhibitor drugs
Key inclusion criteria (5 listed)
- Age ≥18 years.
- Diagnosis of generalized anti-AChR positive Myasthenia Gravis.
- Need for therapy with neonatal Fc receptor inhibitors for immunoglobulins (FcRn) as per AIFA-approved therapeutic indications (14).
- Ability to follow up at the reference center.
- Signed informed consent for the study.
Key exclusion criteria (6 listed)
- Age \<18 years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identification of Clinical Markers of Favorable Response to FcRn Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Time frame: 24 months
Analyze the clinical status of patients comparing the results of MG-ADL clinical scale pre/post FcRn Inhibitors
Identification of Biological and Cellular Markers of Favorable Response to FcRn Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Time frame: 24 months
Analyze the differences between IgG levels pre/post therapy with FcRn inhibitors
Identification of Biological and Cellular Markers of Favorable Response to FcRn Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Time frame: 24 months
• Evaluate anti-AChR positivity in patients treated with FcRn inhibitors
Identification of Biological and Cellular Markers of Favorable Response to FcRn Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Time frame: 24 months
• Dosage of proteins involved in pathogenesis
Identification of Genetic Markers of Favorable Response to FcRn Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Time frame: 24 months
Investigate the presence of polymorphisms in the FCGRT gene (VTNRs) in patients refractory to therapy with FcRn inhibitors
Identification of Clinical Markers of Favorable Response to FcRn Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Time frame: 24 months
Analyze the clinical status of patients comparing the results of QMG clinical scale pre/post FcRn Inhibitors
1 secondary outcome
Predictive algorithm of favorable response
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2024.
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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.
Raffaele Iorio principal investigator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Myasthenia Gravis Generalized, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
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 5 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 12 Nov 2024. 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 Italy. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Raffaele Iorio, MD, PhD (+390630154807, raffaele.iorio@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of Clinical Markers of Favorable Response to FcRn Inhibitors Therapy in Patients With Generalized Myasthenia Gravis (time frame: 24 months). The study lists 6 primary outcomes in all. 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 12 Nov 2024.