CMS, Congenital Myasthenic Syndrome
Conditions
Brief summary
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
Interventions
BIOLOGICALAdimanebart IV
Intravenous infusion of Adimanebart
OTHERPlacebo IV
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
12 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline at week 24 in 6MWT distance | Up to 24 weeks | The 6-minute walk test (6MWT) measures the distance a participant walks in 6 minutes. |
| Incidence of AEs and SAEs | up to 104 weeks | AE: adverse event; SAE: serious adverse event |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in 6MWT distance over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | The 6-minute walk test (6MWT) measures the distance a participant walks in 6 minutes. |
| Change from baseline in PROMIS PF-10b T-score over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | 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) |
| Change from baseline in QMG key component composite score over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | 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). |
| Change from baseline in 6MWT cadence over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | 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. |
| Change from baseline in the QMG key component raw values and scores over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | 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). |
| Change from baseline in PROMIS PF-WMA-SF T-score over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | 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). |
| Change from baseline in Neuro-QoL Short Form-Fatigue T-score over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | 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. |
| Change from baseline in FVC over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | FVC: forced vital capacity to assess pulmonary function |
| Change from baseline in the Actigraphy measures over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | Participants will be asked to wear a wrist-worn actigraphy device to assess physical behaviour and mobility. |
| Change from baseline in PGI-C over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | 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). |
| Change from baseline in PGI-S over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | 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). |
| Change from baseline in CGI-C over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | 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) |
| Change from baseline in CGI-S over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | 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). |
| Change from baseline in EQ-5D-5L over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | The participant-completed EQ-5D-5L questionnaire is a standardized test recognized by many health authorities as a generic measure of health status. |
| Incidence of AEs and SAEs | up to 24 weeks | AE: adverse event; SAE: serious adverse event |
| Adimanebart serum concentrations over time | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | PK=pharmacokinetic(s) |
| Incidence of ADA against adimanebart | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | ADA: Anti-drug antibodies |
| Incidence of NAb against adimanebart | up to 24 weeks (DBTP) + up to 104 weeks (OLE) | Nab: neutralizing antibody(ies) |
Contacts
CONTACTSabine Coppieters, MD
Outcome results
None listed