Antigen-specific immune therapy (CNP-106) for treatment of generalised myasthenia gravis: rationale and design of first-in-human randomised controlled trial.

Introduction: Myasthenia gravis (MG) is a T cell-dependent B cell-mediated autoimmune disease with pathogenic antibodies directed against components of the acetylcholine receptor (AChR). Current therapies do not address the root cause of the disease (autoimmune recognition of AChR) and are associated with possible serious side effects. Therefore, new therapeutic options targeting antigen-specific autoimmunity are needed. COUR nanoparticle (CNP-106) is an antigen-specific immune tolerance therapy directed to the AChR to stop the pathogenic driver of MG. Data from experimental models suggest the potential benefit of CNP-106 to patients by reprogramming the immune system to AChR and stopping the progression of the disease. The aim of this study is to determine the safety and preliminary efficacy of CNP-106 in AChR antibody-positive generalised MG subjects.

Methods and analysis: The outlined study is a multicentre Phase 1b/2a double-blind, randomised, placebo-controlled trial with an enrolment target of 54 AChR antibody-positive generalised MG subjects. The primary endpoint is safety and tolerability. Exploratory and secondary endpoints include disease-specific clinical scores, measures of quality of life and activities of daily living, antigen-specific T cells and AChR antibodies. Trial enrolment is anticipated to start in 2024.

Ethics and dissemination: The trial has ethical approval from the Central Institutional Review Boards and has clinical trial authorisation from the Food and Drug Administration. Trial results will be communicated to participants, presented at national and international meetings and published in peer-reviewed journals.

Trial registration number: NCT06106672.