CMS, Congenital Myasthenic Syndrome
Conditions
Brief summary
The purpose of this study is to assess the safety and tolerability of ARGX-119 in adult participants with DOK7- Congenital Myasthenic Syndromes. The study will also assess how ARGX-119 is processed by the body (pharmacokinetics), how the immune system reacts to it (immunogenicity), and how it may improve the way patients feel and function. After the screening period, eligible participants will be randomized in a 4:1 ratio to receive intravenous infusions of ARGX-119 or placebo during the double-blinded treatment period. Participants will then enter the follow-up period. After the follow-up period, participants may enrol in the active-treatment period, where they will receive open-label ARGX-119. The full duration of the study is approximately 38 months.
Interventions
BIOLOGICALARGX-119
Intravenous infusion of ARGX-119
OTHERPlacebo
Intravenous infusion of placebo
Sponsors
argenx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years of age. * Has genetically confirmed congenital myasthenic syndromes due to mutation of downstream of kinase 7 (DOK7-CMS). * Participants taking oral beta agonists (eg, albuterol, salbutamol, ephedrine) must have been receiving the medication for more than 3 months and agree to remain on a same stable dosing regimen of the same medication until the end of the study.
Exclusion criteria
* Diagnosis of CMS due to mutation of any gene other than DOK7. * 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. * History of malignancy, cancer, unless considered cured by adequate treatment with no evidence of recurrence for more than 5 years. Adequately treated participants with the following cancers can be included at any time: Basal cell or squamous cell skin cancer, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histological findings of prostate cancer. * Pregnant or lactating state or intention to become pregnant during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of adverse events (AEs) | Up to week 42 | — |
| Change from active-treatment baseline over time for 6MWT distance | Up to 72 weeks | The 6-minute walk test (6MWT) measures the distance a participant walks in 6 minutes. Before and after the 6MWT assessment, the participant's blood pressure, heart rate, and SPO2 will be recorded, and the participant's perception of fatigue and dyspnea will be measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed serum concentration (Cmax) of ARGX-119 | Up to 42 weeks + 72 weeks | — |
| Incidence of ADA against ARGX-119 | Up to 42 weeks + 72 weeks | ADA : anti-drug antibodies |
| Change from baseline over time for key components of the QMG scale | Up to 42 weeks + 72 weeks | 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: 39 (highest disease severity). The change from active-treatment baseline will be used for the 72 week timepoint. |
| Change from baseline over time for MG-ADL | Up to 42 weeks + 72 weeks | The Myasthenia Gravis Activities of Daily Living (MG-ADL) is an 8-item scale that assesses MG symptoms and their effects on daily activities. Minimum value: 0 (normal symptoms); Maximum value: 24 (most severe symptoms). The change from active-treatment baseline will be used for the 72 week timepoint. |
| Change from baseline over time for PROMIS-GH scale | Up to 42 weeks | The Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) is a 10-item participant completed quality of life questionnaire that measures global physical health and mental health. The participant records their response to each question on a 5-point Likert scale, with lower scores indicating poorer health (Minimum value: 0, Maximum value: 20) |
| Change from active-treatment baseline over time for 6MWT cadence | Up to 72 weeks | The 6-minute walk test (6MWT) measures the distance a participant walks in 6 minutes. Before and after the 6MWT assessment, the participant's blood pressure, heart rate, and SPO2 will be recorded, and the participant's perception of fatigue and dyspnea will be measured. |
| Change from active-treatment baseline over time for PROMIS PF-WMA-SF | Up to 72 weeks | The PROMIS PF-WMA-SF 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 0 (unable to do). |
| Change from active-treatment baseline over time for Neuro-QoL fatigue | Up to 72 weeks | — |
| Change from active-treatment baseline over time for FVC | Up to 72 weeks | — |
| Change from active-treatment baseline over time for PGI-C | Up to 72 weeks | — |
| Change from active-treatment baseline over time for PGI-S | Up to 72 weeks | — |
| Change from active-treatment baseline over time for CGI-C | Up to 72 weeks | — |
| Change from active-treatment baseline over time for CGI-S | Up to 72 weeks | — |
| Change from active-treatment baseline over time for EQ-5D-5L | Up to 72 weeks | — |
| Incidence of AEs and SAEs | Up to 72 weeks | AE : Adverse events ; SAE : Serious Adverse events |
Countries
Canada, France, Italy, Spain, United Kingdom, United States
Outcome results
None listed