A Study to Assess Efficacy and Safety of Adimanebart in Adult and Pediatric Participants With DOK7-,MUSK-, AGRN-, or LRP4- Congenital Myasthenic Syndromes (CMS) (CoMetS)

Phase 3, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study With an Open-Label Extension to Evaluate the Efficacy and Safety of Intravenous Adimanebart in Adult and Pediatric Participants With DOK7-,MUSK-, AGRN-, or LRP4-CMS

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 Overview

• Status: Not yet recruiting
• Conditions: Congenital Myasthenic Syndrome; CMS
• Intervention / Treatment: Biological: Adimanebart IV; Other: Placebo IV

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sabine Coppieters, MD; Phone Number: 857-350-4834; Email: Clinicaltrials@argenx.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

DBTP:

• At least 12 years of age.
• Has a diagnosis of DOK7-, MUSK-, AGRN-, or LRP4-CMS with documented mutations.
• Participants taking oral beta agonists (eg, albuterol, salbutamol, ephedrine) or other CMS medication must have been receiving the medication for at least 6 months and agree to remain on a same stable dosing regimen of the same medication unless directed to change their CMS medication(s) by their treating physician.

OLE:

• Completed part of the active-treatment period of ARGX-119-2302.

Exclusion Criteria:

DBTP:

• Known medical condition that would interfere with an accurate assessment of CMS, confound the results of the study, or put the patient at undue risk, as assessed by the investigator.

OLE:

• Investigational study drug discontinuation in ARGX-119-2302.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Double-blinded treatment period (DBTP) - Adimanebart IV; Participants randomized to receive Adimanebart IV	Biological: Adimanebart IV; Intravenous infusion of Adimanebart
Placebo Comparator: Double-blinded treatment period (DBTP) - Placebo IV; Participants randomized to receive Placebo IV	Other: Placebo IV; Intravenous infusion of Placebo
Experimental: Open-label extension (OLE) - Adimanebart IV; Participants receive Adimanebart IV	Biological: Adimanebart IV; Intravenous infusion of Adimanebart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline at week 24 in 6MWT distance	The 6-minute walk test (6MWT) measures the distance a participant walks in 6 minutes.	Up to 24 weeks
Incidence of AEs and SAEs	AE: adverse event; SAE: serious adverse event	up to 104 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in 6MWT distance over time	The 6-minute walk test (6MWT) measures the distance a participant walks in 6 minutes.	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)	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).	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.	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).	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).	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.	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	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.	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).	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).	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)	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).	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.	up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Incidence of AEs and SAEs	AE: adverse event; SAE: serious adverse event	up to 24 weeks
Adimanebart serum concentrations over time	PK=pharmacokinetic(s)	up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Incidence of ADA against adimanebart	ADA: Anti-drug antibodies	up to 24 weeks (DBTP) + up to 104 weeks (OLE)
Incidence of NAb against adimanebart	Nab: neutralizing antibody(ies)	up to 24 weeks (DBTP) + up to 104 weeks (OLE)

Collaborators and Investigators

• Sponsor: argenx

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030

Study Registration Dates

• First Submitted: July 30, 2026
• First Submitted That Met QC Criteria: July 30, 2026
• First Posted (Actual): August 4, 2026

Study Record Updates

• Last Update Posted (Actual): August 4, 2026
• Last Update Submitted That Met QC Criteria: July 30, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Neuromuscular Junction Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myasthenic Syndromes, Congenital
• Other Study ID Numbers: ARGX-119-17-CMS-3001; 2025-524460-37-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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