Proteomic Changes in Patients With Myasthenia Gravis and Ravulizumab (PROMPT)

Identification of Proteomic Changes in Patients With Generalized Myasthenia Gravis Treated With Ravulizumab: Insights Into Neuromuscular Junction Regeneration

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder primarily caused by antibodies targeting postsynaptic components of the neuromuscular junction, most commonly the acetylcholine receptor (AChR). In AChR-positive generalized MG, IgG1 and IgG3 antibodies activate the classical complement pathway, leading to membrane attack complex-mediated damage of the postsynaptic membrane and impaired neuromuscular transmission. Complement inhibition has therefore emerged as an effective therapeutic strategy.

Ravulizumab, a long-acting monoclonal antibody targeting complement component C5, has demonstrated clinical efficacy in reducing disease severity in patients with AChR-positive generalized MG. However, clinical responses to complement inhibition remain heterogeneous, and reliable biomarkers to monitor treatment response and neuromuscular junction recovery are currently lacking.

Blood-based proteomics represents a powerful approach for identifying molecular changes associated with disease activity and treatment response. In particular, aptamer-based proteomic platforms such as the SomaScan® assay allow high-throughput, highly sensitive quantification of thousands of circulating proteins from small volumes of plasma or serum.

The primary aim of this study is to identify proteomic changes in patients with generalized MG treated with Ravulizumab, with a specific focus on proteins involved in neuromuscular junction regeneration and repair. By leveraging advanced proteomic technologies in a real-world clinical setting, this study seeks to identify biomarkers that may help monitor treatment response, guide optimization of concomitant immunosuppressive therapies, and improve patient stratification. Ultimately, the identification of molecular pathways associated with neuromuscular junction regeneration may open new therapeutic perspectives for autoimmune neuromuscular disorders.

Study Overview

• Status: Not yet recruiting
• Conditions: Myasthenia Gravis Generalised

• Study Type: Observational
• Enrollment (Estimated): 24

Contacts and Locations

• Study Contact: Name: Raffaele Iorio, MD, PhD; Phone Number: +390630154807; Email: raffaele.iorio@policlinicogemelli.it
• Study Contact Backup: Name: Sofia Marini, MD; Phone Number: +390630154807; Email: sofiamarini97@gmail.com

Study Locations

• Italy
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario A. Gemelli IRCCS
    • Contact: Raffaele Iorio, MD, PhD; Phone Number: +390630154807; Email: raffaele.iorio@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with generalized Myasthenia Gravis positive for anti-AChR antibodies undergoing therapy with Ravulizumab

Description

Inclusion Criteria:

• Age ≥18 years;
• Diagnosis of generalized anti-AChR positive Myasthenia Gravis;
• Need for therapy with Ravulizumab drugs according to the therapeutic indications approved by AIFA;
• Signed informed consent to the study.

Exclusion Criteria:

• Age <18 years;
• Concomitant autoimmune diseases;
• Insufficient availability of clinical information;
• Ongoing neoplasia or infection at the time of biological sample collection

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To identify significant changes in plasma protein profiles in patients with generalized myasthenia gravis (gMG) treated with Ravulizumab.	To identify changes in plasma proteins after 10 and 26 weeks of treatment with Ravulizumab compared with baseline, using proteomic technology.	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To identify plasma proteins associated with a clinically meaningful improvement in patients with gMG.	To analyze correlations between plasma protein profiles and clinical outcome measures in patients with gMG after 10 and 26 weeks of treatment with Ravulizumab.	26 weeks
To identify potential biomarkers of neuromuscular junction regeneration in patients with gMG.	To create a dedicated database and perform a literature review to determine whether any of these proteins may represent potential biomarkers of neuromuscular junction regeneration in patients with gMG.	24 months

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Collaborators: Alexion Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Raffaele Iorio, Prof, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: December 19, 2025
• First Submitted That Met QC Criteria: January 7, 2026
• First Posted (Actual): January 13, 2026

Study Record Updates

• Last Update Posted (Actual): January 13, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Myasthenia Gravis; Ravulizumab; Proteomic changes
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myasthenia Gravis
• Other Study ID Numbers: 8167 (CTEP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No