An Open-label Study to Investigate the Clinical Efficacy of Different Dosing Regimens of Efgartigimod IV in Patients With Generalized Myasthenia Gravis

Study Overview
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Brief Summary
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The purpose of this open-label study is to investigate the efficacy, safety, and tolerability of a continuous regimen of efgartigimod compared with a cyclic regimen in participants with Generalized Myasthenia Gravis (gMG). Study details include: The study duration will be up to 138 weeks (including screening and a safety follow-up of up to 9 weeks) Part A (regimen comparison period) - 21 weeks Part B (extension period) - up to 105 weeks The visit frequency, including virtual visits, will be weekly through Week 21 and every 5 weeks for the remainder of the study.

Official Title
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A Phase 3b, Randomized, Open-label, Parallel-Group Study to Evaluate Different Dosing Regimens of Intravenous Efgartigimod to Maximize and Maintain Clinical Benefit in Patients With Generalized Myasthenia Gravis

Conditions
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Generalized Myasthenia Gravis

Intervention / Treatment
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* Biological: Efgartigimod concentrate for solution for infusion 20 mg/mL
* Biological: Efgartigimod concentrate for solution for infusion 20 mg/mL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. At least 18 years of age, at the time of signing the informed consent. Diagnosed with Generalized Myasthenia Gravis (gMG) with confirmed documentation and supported by a physical exam and confirmed seropositivity for anti-acetylcholine receptor antibodies (AChR-Abs). Meets the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, or IV Has an Myasthenia Gravis - Activities of Daily Living (MG-ADL) total score ≥5 at screening and the day 1 visit, with more than 50% of the score due to nonocular symptoms Concomitant gMG treatment is permitted. Permitted concomitant gMG treatment includes nonsteroidal immunosuppressive drugs (NSIDs), steroids, and/or acetylcholinesterase (AChE) inhibitors. If receiving corticosteroids and/or NSIDs, must be on a stable dose for at least 1 month before screening. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and: Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before investigational medicinal product (IMP) can be administered. Exclusion Criteria: Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening A positive test for SARS-CoV-2 at screening Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of the clinical symptoms of gMG and/or put the participant at undue risk 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, provided they are adequately treated at screening: Basal cell or squamous cell skin cancer; carcinoma in situ of the cervix; Carcinoma in situ of the breast; Incidental histological finding of prostate cancer (TNM stage T1a or T1b) Clinical evidence of other significant serious diseases, a recent (<3 months) major surgery, or any other condition that, in the opinion of the investigator, could confound the results of the study or put the participant at undue risk A thymectomy within 3 months of screening Pregnant or lactating females and those who intend to become pregnant during the study or within 90 days of the last dose of IMP Use of the following prior or concomitant therapies: intravenous immunoglobulin (IVIg) or subcutaneous immunoglobulin (SCIg) within 14 days of day 1 Rituximab within 6 months of day 1 Eculizumab within 1 month of day 1 Other monoclonal antibodies (eg, adalimumab, tocilizumab, ixekizumab) within 5 half-lives of the monoclonal antibodies before day 1 Use of any other investigational product within 3 months or 5 half-lives, whichever is longer, before day 1 Receipt of a live or live-attenuated vaccines received within 4 weeks of screening. The receipt of any inactivated, subunit, polysaccharide, conjugate vaccine at any time before screening is not considered exclusionary. Previous participation in a clinical study or patient access program during which they were treated with efgartigimod Positive serum test at screening for an active viral infection with any of the following conditions: Hepatitis B virus (HBV) that is indictive of an acute or chronic infection; Hepatitis C virus (HCV) based on HCV antibody assay (unless associated with a negative HCV RNA test); HIV based on test results that are associated with an AIDS-defining condition or a CD4 count <200 cells/mm3 Total IgG <6 g/L at screening Known hypersensitivity reaction to efgartigimod or any of its excipients The participant stands in any relationship of dependency with the sponsor. The participant has been institutionalized due to an official or judicial order.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: efgartigimod IV - I<br>Patients receiving efgartigimod IV treatment (Continuous regimen: efgartigimod 10 mg/kg q2w) | Biological: Efgartigimod concentrate for solution for infusion 20 mg/mL<br>* Patients receiving efgartigimod IV treatment in a continuous treatment regimen<br>* Other names: Efgartigimod IV;|
| Experimental: efgartigimod IV - II<br>Patients receiving efgartigimod IV treatment (Cyclic regimen: efgartigimod 10 mg/kg q7d for a total of 4 infusions per TP for 2 TPs with a fixed 4-week IP between each TP) | Biological: Efgartigimod concentrate for solution for infusion 20 mg/mL<br>* Patients receiving efgartigimod IV treatment in a cyclic treatment regimen<br>* Other names: Efgartigimod IV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of the average Myasthenia Gravis - Activities of Daily Living (MG-ADL) total score change from baseline during the visit of week (W)1 through W21 by regimen arm. A higher total score indicates more impairment. |  | 21 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESIs) |  | 136 weeks | 
| Incidence of serious adverse events (SAEs) and AEs of special interest (AESIs) |  | 136 weeks | 
| Change from baseline in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) total score over time. A higher total score indicates more impairment. |  | 126 weeks | 
| Normalized area under the effect curve (AUEC) of MG-ADL total score improvement from baseline during following intervals: Day 1 through Week7, Week 7 through Week 14, Week 14 trough Week 21 and Week 7 through Week 21 |  | 21 weeks | 
| Characterization of MG-ADL total score change from baseline during the following 5 intervals using mean and standard deviation: Week 1 through Week 7, Week 8 through Week 14, Week 15 through Week 21, Week 8 through Week 21 and Week 1 through Week 21. |  | 21 weeks | 
| Number of participants who have a ≥2, 3, 4, or 5 points improvement in MG-ADL total score from baseline. during the following 5 intervals: W1 through W7, W8 through W14, W15 through W21, W8 through W21 and W1 through W21. |  | 21 weeks | 
| Percentage of participants who have a ≥2, 3, 4, or 5 points improvement in MG-ADL total score from baseline during the following 5 intervals: W1 through W7, W8 through W14, W15 through W21, W8 through W21 and W1 through W21. |  | 21 weeks | 
| Percentage of time, participants have a change in MG-ADL total score of at least 2 points from baseline during Week 4 through Week 21. |  | 21 weeks | 
| Number of participants who achieve minimal symptom expression (MSE), defined as a MG-ADL total score of 0 or 1 |  | 21 weeks | 
| Percentage of participants who achieve minimal symptom expression (MSE), defined as a MG-ADL total score of 0 or 1 in the following 5 intervals: W1 though W7, W8 through W14, W15 through W21, W8 through W21 and W1 through W21. |  | 21 weeks |