Targeting Collagen VII Antibodies in Bullous Diseases Using Efgartigimod IV (VYVGART)

Inclusion criteria

• For DEB patients (aged 12 years or older): DEB confirmed with mutation analysis and correlated by phenotype, and treatment of at least 1 wound treated with topical gene therapy (VYJUVEK). Presence of C7 antibodies above normal cutoff on ELISA.
• For (classic) EBA patients (aged 18 years or older): EBA confirmed with positive histopathology (DIF), C7 antibodies above normal cutoff on ELISA, and having at least 1 skin lesion.
• The participant has a Karnofsky performance status of at least 60% at screening.
• Contraceptive use by reproductive male and female patients should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and:

• Male participants:

• Must agree to use an acceptable method of contraception and not donate sperm from the time that the ICF is signed until they have received their last dose of IMP.
• Female participants:

• Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at week 1 / baseline before study intervention can be administered. Subsequent urine pregnancy tests are to be completed at week 6, week 11, week 16, week 21, and week 26 / EoS.
• WOCBP must agree to use a highly effective or acceptable contraception method until at least 90 days after they receive their last dose of IMP.

Exclusion criteria

• Linear IgA dermatosis-like EBA or other autoimmune blistering diseases (including but not limited to pemphigus vulgaris, bullous pemphigoid, mucous membrane pemphigoid).
• Use of the following EBA treatments:

• sulfasalazine, IVIg, subcutaneous administration of immunoglobulin (SCIg), immunoadsorption or plasma exchange within 2 weeks of the screening visit, tetracyclines with or without nicotinamide at doses higher than the recommended daily allowance (RDA)/dietary reference intake (DRI) within 2 weeks of the screening visit.
• any monoclonal antibody (including rituximab or another anti-CD20 biologic) within 6 months of the screening visit.
• complementary therapies-such as traditional Chinese medicines, herbs, or procedures (e.g., acupuncture)-within 4 weeks (or 5 half-lives) of the screening visit, if the investigator determines that such therapies may interfere with the study's efficacy assessments and/or potentially risk the safety of the participant.
• The use of the following EBA treatments is permitted throughout the study: OCS, topical corticosteroids, conventional immunosuppressants (e.g., azathioprine, cyclophosphamide, methotrexate, mycophenolate, or mofetil), and dapsone.
• Moderate to severe renal insufficiency.
• Known contraindication to OCS therapy.
• Clinically significant uncontrolled active or chronic, bacterial, viral, or fungal infection at screening
• Medical instability limiting ability to travel to the Investigative Center
• Diseases or conditions that could interfere with the assessment of safety and efficacy of the study treatment and compliance of the subject with study visits/procedures, as determined by the investigator.
• Subjects actively receiving chemotherapy or immunotherapy at screening
• Active drug or alcohol addiction as determined by the investigator.
• Pregnant or nursing women
• 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, provided they are adequately treated prior to 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)