A Natural History Study in Participants With Congenital Myasthenic Syndromes (CMS) Due to Mutations in DOK7, MUSK, AGRN, or LRP4

Recruiting

• Conditions: Congenital Myasthenic Syndrome

• Registration Number: NCT06078553
• Lead Sponsor: argenx

Brief Summary

Participants will attend up to 4 study visits to collect clinical assessments. The assessments will evaluate participants' symptoms and quality of life to understand disease activity in patients with CMS due to mutations in DOK7, MUSK, AGRN, or LRP4.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-08
• Study First Submitted QC: 2023-10-09
• Study First Posted: 2023-10-12
• Study Start: 2024-02-13
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-11
• Primary Completion: 2027-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Can understand the requirements of the study and can provide written informed consent/assent, and willingness and ability to comply with the study protocol procedures
• Is male or female and aged ≥2 years at the time of providing informed consent/assent
• Has a diagnosis of CMS due to biallelic pathogenic mutations in DOK7 or any pathogenic mutations in MUSK, AGRN, or LRP4
• Has a total Quantitative Myasthenia Gravis (QMG) score of ≥3 (applies only to participants aged ≥6 years)
• For participants taking oral beta agonists (eg, albuterol, salbutamol, ephedrine), participant must have been receiving the medication for ≥3 months before screening/baseline

Exclusion Criteria

• Known medical condition that would interfere with an accurate assessment of CMS, in the investigator's opinion
• Is currently participating in any interventional clinical study with a study drug at the time of providing informed consent/assent
• Diagnosis of CMS due to mutation of any gene other than DOK7, MUSK, AGRN, or LRP4

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Summary statistics of retrospective and prospective collection of data on diagnosis.	Up to 12 months
Summary statistics of retrospective and prospective collection of data on health care utilization.	Up to 12 months
Summary statistics of retrospective and prospective collection of data on medications.	Up to 12 months
Summary statistics of retrospective and prospective collection of data on change in health status related to CMS	Up to 12 months

Secondary Outcome Measures

Name	Time	Method
Change from baseline for QMG total score, each component score, and raw values	Up to 12 months	The Quantitative Myasthenia Gravis (QMG) consists of 13 items that assess ocular, bulbar, and limb function. Six of the 13 items are timed endurance tests measured in seconds. Each item has a possible score from 0 to 3, with 3 being the most severe. The total possible score is 39, with higher scores indicating more severe impairments.
Change from baseline for MG-ADL total score	Up to 12 months	The Myasthenia Gravis Activities of Daily Living (MG-ADL) is an 8-item scale that assesses MG symptoms and their effects on daily activities. The 8 items are rated by the participant on a scale of 0 to 3. The total score can range from 0 to 24, with higher total scores indicating more impairment.
Change from baseline for Neuro-QoL Fatigue score	Up to 12 months	The Quality of Life in Neurological Disorders (Neuro-QoL) Fatigue questionnaire will be completed by participants aged ≥18 years. The Neuro-QoL Pediatric Fatigue questionnaire will be completed by pediatric participants aged ≥12 to \<18 years. Participants aged \<8 years will be evaluated using the proxy version of the questionnaire.
Change from baseline for PROMIS-GHS	Up to 12 months	The Patient-Reported Outcomes Measurement Information System Global Health Scale (PROMIS-GHS) is a quality-of-life questionnaire that comprises questions on overall physical health, physical function, pain, and fatigue (GPH); and quality of life, mental health, satisfaction with social activities, and emotional problems (GMH). The participant marks their response on a 5-point Likert scale, with lower scores indicating poorer health
Change from baseline for PROMIS-DFL	Up to 12 months	The Patient-Reported Outcomes Measurement Information System Dyspnea Functional Limitations (PROMIS-DFL) is a questionnaire that evaluates the impact of dyspnea on the ability to perform daily activities within the last 7 days. The participant marks their response on a 4-point scale (0 to 3), with lower values indicating less functional impairment.
Change from baseline for EQ-5D-5L	Up to 12 months	The EQ-5D-5L questionnaire is a standardized test recognized by many health authorities as a generic measure of health status for clinical and economic appraisal. The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Participants mark their health status from 0 (the worst health you can imagine) to 100 (the best health you can imagine).
Change from baseline for 3TUG	Up to 12 months	The Triple Timed Up and Go (3TUG) is an objective measure of mobility requiring 3 repetitions (laps) to assess lower extremity weakness and fatigability.

Trial Locations

Locations (10)

The Ottawa Hospital - Civic Campus; 🇨🇦 Ottawa, Canada

CHU Timone; 🇫🇷 Marseille, France

Assistance Publique Hopitaux de Paris - Hopital Pitie-Salpetriere; 🇫🇷 Paris, France

Hospital Universitari i Politecnic La Fe; 🇪🇸 Valencia, Spain

Fondazione IRCCS Istituto Neurologico Carlo Besta; 🇮🇹 Milan, Italy

Ulster Hospital; 🇬🇧 Dundonald, United Kingdom

Oxford University Hospitals NHS Foundation Trust - John Radcliffe Hospital; 🇬🇧 Oxford, United Kingdom

UC Davis Health - UC Davis Health Midtown Ambulatory Care Center; 🇺🇸 Sacramento, California, United States

Ann and Robert H Lurie Children's Hospital of Chicago - Main Hospital; 🇺🇸 Chicago, Illinois, United States

Hospital Sisters Health System (HSHS) - St Elizabeth's Hospital; 🇺🇸 O'Fallon, Illinois, United States