The purpose of this study is to assess efficacy and safety of adimanebart in participants at least 12 years of age with DOK7-, MUSK-, AGRN-, or LRP4- Congenital Myasthenic Syndromes (CMS). The study aims to determine whether adimanebart is safe and can help people with CMS feel better and perform daily activities more easily. The study includes a double-blinded treatment period (DBTP) and an Open- label extension period (OLE). In the DBTP, all participants will be randomized in a 1:1 ratio to adimanebart or placebo. Participants who complete the DBTP will continue to the OLE. Additionally, participants who complete part of the active-treatment period of ARGX-119-2302 study are eligible to enroll in the OLE of this study. In the OLE, all participants will receive open-label adimanebart. After final IMP dose, the participants will enter a follow-up period and their health will be monitored. The total duration of the study is up to approximately 152 weeks (2 years and 11 months). More information can be found here: clinicaltrials.argenx.com/Comets
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
105
Intravenous infusion of Adimanebart
Intravenous infusion of Placebo
Change from baseline at week 24 in 6MWT distance
The 6-minute walk test (6MWT) measures the distance a participant walks in 6 minutes.
Time frame: Up to 24 weeks
Incidence of AEs and SAEs
AE: adverse event; SAE: serious adverse event
Time frame: up to 104 weeks
Change from baseline in 6MWT distance over time
The 6-minute walk test (6MWT) measures the distance a participant walks in 6 minutes.
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Change from baseline in PROMIS PF-10b T-score over time
The PROMIS PF-10b T-score (Patient-Reported Outcomes Measurement Information System Physical Function 10b) is a 10- item, participant-reported short-form questionnaire designed to assess physical function. The questionnaire asks the participant to rate the items on a 5-point Likert scale of 5 (without any difficulty) to 1 (unable to do)
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Change from baseline in QMG key component composite score over time
The Quantitative Myasthenia Gravis (QMG) scale is a standardized quantitative scoring system that was developed to assess disease severity based on impairment of body function and structures in patients with MG. Minimum value: 0 (no disease severity); Maximum value: 15 (highest disease severity).
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Change from baseline in 6MWT cadence over time
The 6-minute walk test (6MWT) measures the distance a participant walks in 6 minutes. Cadence is the number of steps taken per unit of time (steps/min) and is a measure of functional mobility.
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Change from baseline in the QMG key component raw values and scores over time
The Quantitative Myasthenia Gravis (QMG) scale is a standardized quantitative scoring system that was developed to assess disease severity based on impairment of body function and structures in patients with MG. Minimum value: 0 (no disease severity); Maximum value: 15 (highest disease severity).
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Change from baseline in PROMIS PF-WMA-SF T-score over time
The PROMIS PF-WMA-SF T-score (Patient-Reported Outcomes Measurement Information System Physical Function With Mobility Aid Short Form) is an 11-item, participant-completed questionnaire that assesses lower and upper extremity function and associated activities of daily living. The questionnaire asks the participant to rate the items on a 5-point scale of 5 (without any difficulty) to 1 (unable to do).
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Change from baseline in Neuro-QoL Short Form-Fatigue T-score over time
Neuro-QoL Short Form-Fatigue (Quality of Life in Neurological Disorders Short Form - Fatigue) is a participant-completed short-form questionnaire designed to provide a measurement of fatigue in patients with neurological conditions and the impact of their fatigue on their quality of life and daily activities.
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Change from baseline in FVC over time
FVC: forced vital capacity to assess pulmonary function
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Change from baseline in the Actigraphy measures over time
Participants will be asked to wear a wrist-worn actigraphy device to assess physical behaviour and mobility.
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Change from baseline in PGI-C over time
The Patient Global Impression of Change (PGI-C) is a patient-reported rating scale to assess the change in symptom severity and functional problems since the first IMP administration. Participants are asked to rate their change in symptom severity and functional problems on a 7- point Likert scale from 1 (much improved) to 7 (much worse).
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Change from baseline in PGI-S over time
The Patient Global Impression of Severity (PGI-S) scale is a patient-reported rating scale to assess symptom severity and functional problems. Participants are asked to rate their symptom severity and functional problems on a 7-point Likert scale from 1 (no problems) to 7 (unable to do).
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Change from baseline in CGI-C over time
The Clinical Global Impression of Change (CGI-C) scale is a clinician-reported rating scale to assess changes in a participant's symptom severity and functional problems since the first IMP administration. Clinicians are asked to rate the change in the participant's symptom severity and functional problems on a 7-point Likert scale from 1 (much improved) to 7 (much worse)
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Change from baseline in CGI-S over time
The Clinical Global Impression of Severity (CGI-S scale) is a clinician-reported rating scale to assess a participant's symptom severity and functional problems. The scale comprises a single item. Based on clinical judgment, clinicians rate the participant's symptom severity and functional problems on a 4-point Likert scale from 0 (no problems) to 4 (unable to do).
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Change from baseline in EQ-5D-5L over time
The participant-completed EQ-5D-5L questionnaire is a standardized test recognized by many health authorities as a generic measure of health status.
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Incidence of AEs and SAEs
AE: adverse event; SAE: serious adverse event
Time frame: up to 24 weeks
Adimanebart serum concentrations over time
PK=pharmacokinetic(s)
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Incidence of ADA against adimanebart
ADA: Anti-drug antibodies
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Incidence of NAb against adimanebart
Nab: neutralizing antibody(ies)
Time frame: up to 24 weeks (DBTP) + up to 104 weeks (OLE)
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