Generalized Myasthenia Gravis gMG
Conditions
Interventions
Efgartigimod infusion IV. This concerns one infusion in part A, and 4 infusions
in 3 weeks in part B.
Sponsors
argenx BV
Eligibility
Age
2 Years to 17 Years
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the trial only if all of the following criteria apply: 1. Ability of the participant and/or his/her legally authorized representative to understand the requirements of the trial and provide written informed consent/assent, if applicable (including consent/assent for the use and disclosure of research-related health information), willingness and ability to comply with the trial protocol procedures (including attending the required trial visits). 2. Male or female participants between 2 to less than 18 years of age at the time of providing informed consent/assent. Age groups are enrolled in a staggered fashion respectively: 6 participants in the 12 to less than 18 years of age group followed by 6 participants in the 2 to less than 12 years of age group at the time of providing informed consent/assent. 3. Diagnosed with gMG with confirmed documentation 4. Meeting the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, and IVa. 5. Eligible participants should have an unsatisfactory response (efficacy and/or safety) to immunosuppressants, steroids or AChE inhibitors and should be on stable concomitant gMG therapy of adequate duration before screening. 6. Positive serologic test for anti-AChR antibodies at screening (for younger participants (
Exclusion criteria
Exclusion criteria: Participants are excluded from the trial if any of the following criteria apply: 1. Participants with MGFA class I, IVb, and V. 2. Female adolescents of childbearing potential: Pregnancy or lactation, or the participant intends to become pregnant during the trial or within 90 days after the last dose of IMP. 3. Has any of the following medical conditions: a) Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening. b) Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of myasthenia gravis or put the participant at undue risk. c) History of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for >=3 years before the first administration of the IMP. Participants with the following cancers can be included at any time: • Adequately treated 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 (TNM Classification of Malignant Tumors stage T1a or T1b) d) Clinical evidence of other significant serious diseases, or have had a recent major surgery, or who have any other condition that, in the opinion of the investigator, could confound the results of the trial or put the participant at undue risk. 4. Estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73m2 at screening. 5. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2 times the upper limit of normal (ULN) and bilirubin greater than 1.5 × ULN, or any other clinically meaningful abnormalities. 6. Worsening muscle weakness secondary to concurrent infections or medications (aminoglycosides, fluoro-quinolones, beta-blockers, etc). 7. A documented lack of clinical response to plasma exchange (PLEX). 8. Received a live or live-attenuated vaccine fewer than 28 days before screening. (Receiving an inactivated, subunit, polysaccharide, or conjugate vaccine any time before screening is not exclusionary.) 9. Received a thymectomy <3 months before screening or 1 is planned to be performed during the trial period. 10. The following results from these diagnostic assessments will be considered exclusionary: a) Positive serum test at screening for an active viral infection with any of the following conditions: • Hepatitis B virus (HBV) that is indicative of an acute or chronic infection (https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf) • Hepatitis C virus (HCV) based on HCV antibody assay b) Positive HIV serology at screening. c) Positive nasopharyngeal swab PCR test for SARS-CoV-2 at screening. 11. Using the following prior or concomitant therapies: a) Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of the IMP. b) Use of any monoclonal antibody within the 6 months before the first dose of the IMP. c) Use of intravenous immunoglobulin (IVIg), immunoglobulins administered subcutaneously (SC) or intramuscularly, or PLEX within 4 weeks before screening. 12. Total IgG levels below the lower limit of normal (LLN) according to the reference ranges of the central laboratory for participant by sex and age at screening. 13. A known hypersensitivity reaction to efgartigimod or any of its excipients. 14. Current participation in another interventional clinical trial. 15. History (within 12 months of screening) of current alc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efgartigimod concentrations as input for compartmental, model-driven analysis to determine (age and size dependency of) clearance (CL) and volume of distribution (Vd) PD parameters: total IgG levels and anti-acetylcholine receptor antibodies (AChR-Ab) as input for PK/PD modeling analysis | — |
Secondary
| Measure | Time frame |
|---|---|
| • Incidence and severity of adverse events (AEs), incidence of serious AEs (SAEs), incidence of AEs of special interest (AESIs), and changes in laboratory test results, physical examination results, vital sign measurements, and electrocardiogram (ECG) (Part B only for ECGs) • Efgartigimod serum concentrations • Levels of total IgG and AChR-Ab absolute values, change from baseline, and percent (%) reduction from baseline • Incidence and prevalence of antidrug antibodies (ADA) against efgartigimod • MG-ADL total score: absolute value and change from baseline • Total Quantitative Myasthenia Gravis (QMG) score: absolute value and change from baseline • Total score EQ-5D-Y: absolute value and change from baseline • Quality of Life in Neurological Disorders (Neuro-QoL) Pediatric Fatigue Score: values and change from baseline • Change in protective antibody titers to vaccines received before or received during the trial | — |
Countries
Netherlands
Outcome results
None listed