Disease of the neuro muscular junction
Conditions
Interventions
Patients will be randomized in a 1:1 ratio to receive either efgartigimod PH20
SC 1000 mg or efgartigimod IV 10 mg/kg in addition to their concomitant gMG
therapy.
Efgartigimod PH20 SC or efgartig
Sponsors
argenx BV
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: 1. Must be capable of giving signed informed consent as described in Section 10.1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 2. At least 18 years of age at the time of signing the ICF. 3. Diagnosed with gMG with confirmed documentation and supported by at least 1 of the following: a. History of abnormal neuromuscular transmission demonstrated by single fiber electromyography or repetitive nerve stimulation b. History of positive edrophonium chloride test c. Demonstrated improvement in MG signs upon treatment with oral acetylcholinesterase (AChE) inhibitors as assessed by the treating physician 4. Meeting the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, IVa, or IVb 5. Abdominal skin tissue allows for absorption and assessment of local safety of the planned SC injection, as determined by the investigator. 6. An MG-ADL total score of *5 points, with more than 50% of the score due to nonocular symptoms at screening and baseline. 7. Receiving a stable dose of other gMG treatment (concomitant gMG treatment) prior to screening. For patients receiving nonsteroidal immunosuppressants (NSIDs), steroids, and/or AChE inhibitors as concomitant medications, the following dose conditions apply: a. NSIDs (eg, azathioprine, methotrexate, cyclosporine, tacrolimus, mycophenolate mofetil, and cyclophosphamide): treatment initiated at least 6 months prior to screening and no changes to dose in the 3 months before screening. b. Steroids: treatment initiated at least 3 months prior to screening and no dose changes in the month before screening c. AChE inhibitors: stable dose with no dose escalation during the 2 weeks before screening. AChE inhibitors must be withheld for at least 12 hours before the QMG assessment, to be consistent with the revised manual for the QMG test, as recommended by the MFGA. 8. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and: a. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last study dose of the IMP: * Refrain from donating sperm Plus either * Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent Or * Must agree to use a male condom with a female partner using an additionally highly effective contraceptive method with a failure rate of <1% per year as described in Section 10.5. when having sexual intercourse with a woman of childbearing potential who is not currently pregnant Or * Be a sterilized man who has had a documented absence of sperm post-procedure b. Female participants are eligible to participate if they are not pregnant or breastfeeding, and they are 1 of the following: * Women of non-childbearing potential (WONCBP), as defined in Section 10.5.1. Or * Women of childbearing potential (WOCBP) as defined in Section 10.5.1 and is using a contraceptive method that is highly effective (with a failur
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: 1. Are pregnant or lactating, or intend to become pregnant during the study or within 90 days after the last dose of IMP. 2. 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 reoccurrence 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 the participant has had a recent major surgery, or who have any other condition that, in the opinion of the investigator, could confound the results of the study or put the participant at undue risk. 3. Worsening muscle weakness secondary to concurrent infections or medications (aminoglycosides, beta-blockers, etc.) 4. A documented lack of clinical response to plasma exchange (PLEX) 5. Received a live-attenuated vaccine fewer than 28 days before screening. Receiving an inactivated subunit, polysaccharide, or conjugate vaccine any time before screening is not exclusionary. 6. Received a thymectomy <3 months prior to screening or one is planned to be performed during the study period. 7. 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, see Section 10.8) * Hepatitis C virus (HCV) based on HCV antibody assay * Human immunodeficiency virus (HIV) based on a CD4 count of <200 cells/mm3 or test results that are associated with an acquired immunodeficiency syndrome (AIDS)-defining condition, such as: Cytomegalovirus retinitis with loss of vision, Pneumocystis jiroveci pneumonia, chronic intestinal cryptosporidiosis, HIV-related encephalopathy, Mycobacterium tuberculosis (pulmonary or extrapulmonary), or invasive cervical cancer b. Positive nasopharyngeal swab test for SARS-CoV-2 8. 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 IMP b. Use of any monoclonal antibody within 6 months before the first dose of the IMP c. Use of Ig administered intravenously (IVIg), SC (SCIg), or intramuscularly within 4 weeks of screening d. Use of PLEX within 4 weeks of screening e. Previously participated in a clinical study with efgartigimod and/or products co-formulated with rHuPH20 and received at least 1 administration of IMP 9. Total IgG levels <6 g/L at screening 10. Current or history of (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint: * Percent reduction from baseline in total immunoglobulin G (IgG) levels at day 29, ie, 7 days after the fourth IV or SC administration | — |
Secondary
| Measure | Time frame |
|---|---|
| Secundary endpoints: * Absolute values, change from baseline, and percent reduction from baseline in total IgG levels over time * Absolute values, change from baseline, and percent reduction from baseline in acetylcholine receptor binding autoantibodies (AChR-Ab) levels over time in AChR-Ab positive patients * Absolute values, change from baseline, and percent reduction from baseline in IgG subtype levels (IgG1, IgG2, IgG3, and IgG4) over time * Area under the effect curve (AUEC) of the percentage reduction from baseline total IgG and similar AUEC for each IgG subtype per dosing interval (days 1*8, days 8*15, days 15*22, and days 22*29), days 1*29, and over the entire study (days 1*71) * PK parameters: maximum concentration (Cmax) (after all doses for the IV treatment arm), concentration observed predose (Ctrough) * Incidence and prevalence of anti-drug antibodies (ADAs) against efgartigimod * Incidence and prevalence of ADAs against rHuPH20 in the SC treatment arm * Incidence and severity of adverse events (AEs), incidence of serious adverse events (SAEs), and changes in laboratory test results, physical examination results, vital signs, and electrocardiogram (ECG) results * Number and percentage of Myasthenia Gravis Activities of Daily Living (MG-ADL) responders * Number and percentage of Quantitative Myasthenia Gravis (QMG) responders * Change from baseline in MG-ADL total score over time * Change from baseline in QMG score over time | — |
Countries
Netherlands
Outcome results
None listed