An open-label study to investigate the clinical efficacy of different dosing regimens of efgartigimod IV in patients with generalized myasthenia gravis

Phase 1

Conditions: Generalized Myasthenia Gravis (gMG)
MedDRA version: 21.1Level: PTClassification code 10028417Term: Myasthenia gravisSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2021-002504-12-ES

Lead Sponsor: argenx BV

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 72

Inclusion Criteria

1. Capable of giving signed informed consent as described in Section 10.1.3 of the protocol, 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 informed consent
3. Diagnosed with gMG with confirmed documentation and supported by a physical exam and confirmed seropositivity for AChR-Abs
4. Meets the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MFGA) class II, III, or IV
5. Has an MG-ADL total score =5 at screening and the day 1 visit, with more than 50% of the score due to nonocular symptoms
6. 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.
7. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and:
a. Male participants:
- Male participants are not allowed to donate sperm from signing the ICF until the end of the study.
b. Female participants:
- WOCBP (defined in Section 10.4.1 of protocol) must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before IMP can be administered.
- The contraception requirements for WOCBP are described in Section 10.4.2.1 of the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 43
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 29

Exclusion Criteria

1. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening
2. A positive test for SARS-CoV-2 at screening
3. 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
4. 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:
a. Basal cell or squamous cell skin cancer
b. Carcinoma in situ of the cervix
c. Carcinoma in situ of the breast
d. Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
5. 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
6. A thymectomy within 3 months of screening
7. Pregnant or lactating females and those who intend to become pregnant during the study or within 90 days of the last dose of IMP
8. Use of the following prior or concomitant therapies:
a. IVIg or subcutaneous (SC)Ig within 14 days of day 1
b. Rituximab within 6 months of day 1
c. Eculizumab within 1 month of day 1
d. Other monoclonal antibodies (eg, adalimumab, tocilizumab, ixekizumab) within 5 half-lives of the monoclonal antibodies before day 1
e. Use of any other investigational product within 3 months or 5 half-lives, whichever is longer, before day 1
f. Receipt of a live or live-attenuated vaccine within 4 weeks of screening. The receipt of any inactivated, subunit, polysaccharide, conjugate vaccine at any time before screening is not considered exclusionary.
9. Previous participation in a clinical study or patient access program during which they were treated with efgartigimod
10. Positive serum test at screening for an active viral infection with any of the following conditions:
a. Hepatitis B virus (HBV) that is indictive of an acute or chronic infection
b. Hepatitis C virus (HCV) based on HCV antibody assay (unless associated with a negative HCV RNA test)
c. HIV based on test results that are associated with an AIDS-defining condition or a CD4 count =200 cells/mm3
11. Total IgG <6 g/L at screening
12. Known hypersensitivity reaction to efgartigimod or any of its excipients
13. The participant stands in any relationship of dependency with the sponsor.
14. The participant has been institutionalized due to an official or judicial order.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the clinical efficacy of efgartigimod IV 10 mg/kg administered in a q2w continuous regimen compared to that administered in a cyclic regimen;Secondary Objective: • To evaluate the safety and tolerability of both treatment regimens used throughout the study<br>• To assess the clinical efficacy of efgartigimod IV in both treatment regimens over time<br>• To compare the number of participants who achieve maximal clinical effect during different treatment regimens;Primary end point(s): Mean of the average MG-ADL total score change from baseline during the visit of week (W)1 through W21 by regimen arm;Timepoint(s) of evaluation of this end point: 21 weeks

Secondary Outcome Measures

Name	Time	Method

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