Clinical trial NCT04244006: A Pilot Study of the Efficacy and Safety of Dupilumab Versus Placebo in Patients With Netherton Syndrome
Official title: A Randomized Double-blinded Pilot Study of the Efficacy and Safety of Dupilumab Versus Placebo in Patients With Netherton Syndrome
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Netherton Syndrome
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
Collaborators: name: MedSharing
First posted: 2020-01-28
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: one arm with dupilumab (2/3 of patients) and one arm with placebo (1/3 of patients)
Primary purpose: TREATMENT

Brief summary: To date, there are no effective therapy for the management of Netherton Syndrome (NS) Patients use emollients with a limited efficacy on scaling and no efficacy on skin inflammation and pruritus. They may also use topical corticosteroids or calcineurin inhibitors in case of eczematous lesions. The use of therapies targeting skin inflammation has been reported in a few case reports. Their efficacy is very limited and their uses are limited because of the chronicity of the disease, the impaired skin barrier function and the risk for skin infections and skin cancers. Therefore, there is a huge medical need for novel therapies in NS.The expected consequences of this study are that a 16-week course of dupilumab will be more effective than placebo for the treatment of moderate to severe NS Dupilumab could therefore improve skin condition and quality of life.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The severity of the disease of the Netherton Area Severity Assessment score (NASA).
timeFrame: Day 0 and week 16
Secondary outcomes:
measure: Clinical efficacy severity of pruritus and pain
timeFrame: Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
measure: Presence of infections (adverse event)
timeFrame: Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
measure: Quantity of dermocorticosteroids used between each visit will be evaluated by questioning the patient.
timeFrame: Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
measure: QOL score
timeFrame: Day 0, Week 16 and 28
measure: Skin inflammation
timeFrame: Day 0 and week 16
measure: Protease activity
timeFrame: Day 0 and week 16
measure: Microbiome qualitative and quantitative analysis
timeFrame: Day 0 and week 16
measure: Transepidermal water loss (TEWL)
timeFrame: Day 0 and Week 16
measure: Safety of dupilumab
timeFrame: Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
Other outcomes:
Locations:
city: Paris
country: France
facility: Dermatologie Necker
city: Toulouse
country: France
facility: Dermatology
Study officials:
affiliation: Toulouse Hospital
name: Juliette MAZEREEUW-HAUTIER
role: PRINCIPAL_INVESTIGATOR
References: