A Pilot Study of the Efficacy and Safety of Dupilumab Versus Placebo in Patients With Netherton Syndrome

This is a proof of concept (pilot) double-blind randomized placebo-controlled study evaluating the efficacy and safety of dupilumab for the treatment of NS. Patients will be randomized in a 2:1 ratio to receive dupilumab (2 doses of 300 mg), or placebo, at baseline and then 1 dose of dupilumab 300 mg, or placebo, every 2 weeks until week 14 (total of 8 administrations).Moderate to severe NS were selected in order to be able to measure the improvement of skin condition.

Inclusion criteria

• Adult patients affiliated to a social insurance protection regimen.
• Clinical diagnosis of NS (7) (trichorrhexis invaginata, extensive scaling, skin inflammation, allergic manifestations) and absent or marked reduction of LEKTI staining.
• Moderate to severe forms: NASA (Netherton Area Severity Assessment score) score ≥ 5/12 at inclusion.
• Patients able to understand the study procedures including the ability to complete patient-based self-assessment questionnaires.
• Patients who agree to sign the written informed consent.

Exclusion criteria

• Hypersensitivity to dupilumab or its excipients.
• Modification of the usual treatment (emollients and topical corticosteroids used on a regular basis) within 2 weeks before inclusion.
• Treatment with topical calcineurin inhibitors 1 week before inclusion.
• Treatment with oral immunosuppressant (including cyclosporine, methotrexate, azathioprine, mycophenolate mofetil), oral retinoids (acitretin, alitretinoin, isotretinoin) or phototherapy within 4 weeks before inclusion.
• Treatment with immunomodulating biologics (Tumor Necrosis Factor (TNF) inhibitor) 16 weeks before inclusion.
• Treatment with another investigational drug within 8 weeks before inclusion.
• Treatment with a systemic antibiotic within 2 weeks before inclusion.
• Active skin infection requiring the use of a systemic therapy within 2 weeks before the inclusion.
• Any other condition that according to the investigator will impair the ability to evaluate treatment effect.
• Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g., tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis, aspergillosis).
• Current infections including infection with helminthes.
• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study. Women of childbearing age, potentially sexually active, and unwilling to use adequate birth control methods.
• Mental or physical incapacity to fill in the questionnaires.