Myasthenia Gravis, GeneralizedOPTIMISENCT06455709
Markers of Favorable Response to Complement Inhibitors Therapy
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
- 5 Jun 2024to 1 Jun 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 complement inhibitor drugs
Who may be able to join
- Age ≥18 years;
- Diagnosis of generalized anti-AChR positive Myasthenia Gravis;
- Need for therapy with complement inhibitor drugs according to the therapeutic indications approved by AIFA (16);
- Ability to perform follow-up at the reference center;
- Signed informed consent to the study.
Who cannot join
- Age <18 years;
- Poor compliance with drug therapy;
- Concomitant autoimmune diseases;
- Insufficient availability of clinical information;
- Ongoing neoplasia or infection at the time of biological sample collection;
- Refusal to sign the informed consent to the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione Policlinico Universitario A. Gemelli IRCCS
Roma, 00168
Raffaele Iorio, MD, PhD, +390630154807, raffaele.iorio@policlinicogemelli.it
Sofia Marini, +390630154807, sofiamarini97@gmail.com
About this study
Official title: Identification of Clinical, Biological, Cellular and Genetic Markers of Favorable Response Complement Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
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 for the treatment of generalized myasthenia gravis with anti-AChR antibody positivity. Eculizumab, a humanized monoclonal antibody, binds to the complement fragment C5, inhibiting its cleavage into C5a and C5b, and preventing the formation of the terminal complement complex C5b-9 (MAC).
Currently, Eculizumab is approved in Italy for generalized myasthenia gravis associated with anti-acetylcholine receptor antibody positivity.
This class of drugs is generally more effective than conventional immunosuppressive therapies, though it comes with higher costs.
There is heterogeneity among patients in their response to complement inhibitor therapies. Currently, there is no specific evidence indicating which patients may benefit most from this class of treatments. Personalized therapy, considering the predominant pathogenic mechanisms of anti-AChR in individual patients, seems necessary. Interindividual heterogeneity in the autoantibody repertoire could underlie different responses to complement inhibitor therapies. For example, inhibition of the complement cascade in patients whose autoantibodies also block receptors might result in an unsatisfactory treatment response. Moreover, C5 gene polymorphisms could explain a lack of response to these new drugs. Investigating the immune, genetic, and cellular profile of myasthenic patients eligible for these new pharmacological therapies could be useful for identifying predictive markers of response and personalizing 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 Complement Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
- Analyze the clinical status of patients comparing the results of MG-ADL and QMG clinical scales pre/post complement inhibitors therapy.
Measured: 24 months
Identification of Biological and Cellular Markers of Favorable Response to Complement Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Analyze the differences between complement proteins pre/post therapy with complement inhibitor drugs.
Measured: 24 months
Identification of Biological and Cellular Markers of Favorable Response to Complement Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Measure the levels of proteins involved in the pathogenesis of the disease.
Measured: 24 months
Identification of Genetic Markers of Favorable Response to Complement Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Investigate the presence of polymorphisms in the gene encoding the complement protein C5 in patients refractory to therapy with complement inhibitors.
Measured: 24 months
Secondary outcomes (1)
Predictive algorithm of favorable response
Create a predictive algorithm for response to complement 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 Jun 2024
- Study start5 Jun 2024
- Primary completion1 Jun 2026 (estimated)
- Study completion1 Jun 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
- NCT06455709
- Sponsor's protocol ID
- 6743
- Acronym
- OPTIMISE
- Status last verified
- Jul 2025
- First submitted
- 3 Jun 2024
- Last updated
- 1 Aug 2025
- 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 1 Aug 2025. 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 Complement Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
- ClinicalTrials.gov ID
- NCT06455709
- Acronym / sponsor ID
- OPTIMISE / 6743
- Conditions
- Myasthenia Gravis, Generalized
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 5 Jun 2024 (actual)
- Primary completion
- 1 Jun 2026 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 12 Jun 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 for the treatment of generalized myasthenia gravis with anti-AChR antibody positivity. Eculizumab, a humanized monoclonal antibody, binds to the complement fragment C5, inhibiting its cleavage into C5a and C5b, and preventing the formation of the terminal complement complex C5b-9 (MAC).
Currently, Eculizumab is approved in Italy for generalized myasthenia gravis associated with anti-acetylcholine receptor antibody positivity.
This class of drugs is generally more effective than conventional immunosuppressive therapies, though it comes with higher costs.
There is heterogeneity among patients in their response to complement inhibitor therapies. Currently, there is no specific evidence indicating which patients may benefit most from this class of treatments. Personalized therapy, considering the predominant pathogenic mechanisms of anti-AChR in individual patients, seems necessary. Interindividual heterogeneity in the autoantibody repertoire could underlie different responses to complement inhibitor therapies. For example, inhibition of the complement cascade in patients whose autoantibodies also block receptors might result in an unsatisfactory treatment response. Moreover, C5 gene polymorphisms could explain a lack of response to these new drugs. Investigating the immune, genetic, and cellular profile of myasthenic patients eligible for these new pharmacological therapies could be useful for identifying predictive markers of response and personalizing 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 complement inhibitor drugs
Key inclusion criteria (5 listed)
- Age ≥18 years;
- Diagnosis of generalized anti-AChR positive Myasthenia Gravis;
- Need for therapy with complement inhibitor drugs according to the therapeutic indications approved by AIFA (16);
- Ability to perform follow-up at the reference center;
- Signed informed consent to the study.
Key exclusion criteria (6 listed)
- Age <18 years;
- Poor compliance with drug therapy;
- Concomitant autoimmune diseases;
- Insufficient availability of clinical information;
- Ongoing neoplasia or infection at the time of biological sample collection;
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 Complement Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Time frame: 24 months
- Analyze the clinical status of patients comparing the results of MG-ADL and QMG clinical scales pre/post complement inhibitors therapy.
Identification of Biological and Cellular Markers of Favorable Response to Complement Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Time frame: 24 months
Analyze the differences between complement proteins pre/post therapy with complement inhibitor drugs.
Identification of Biological and Cellular Markers of Favorable Response to Complement Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Time frame: 24 months
Measure the levels of proteins involved in the pathogenesis of the disease.
Identification of Genetic Markers of Favorable Response to Complement Inhibitors Therapy in Patients With Generalized Myasthenia Gravis
Time frame: 24 months
Investigate the presence of polymorphisms in the gene encoding the complement protein C5 in patients refractory to therapy with complement inhibitors.
1 secondary outcome
Predictive algorithm of favorable response
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2025.
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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.
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: looking for participants now, as of the sponsor's last update on 1 Aug 2025. 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?
This study is still under way. Results are not available in the source record yet.
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 Complement Inhibitors Therapy in Patients With Generalized Myasthenia Gravis (time frame: 24 months). The study lists 4 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 1 Aug 2025.