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

Netherton Syndrome Clinical Trial

— NS-DUPI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04244006
• Other study ID #: RC31/19/0045
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: July 23, 2020
• Est. completion date: June 1, 2024

Study information

• Verified date: August 2023
• Source: University Hospital, Toulouse
• Contact: Nadège ALGANS
• Phone: 0561777204
• Email: algans.n[@]chu-toulouse.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: June 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Netherton Syndrome
• Syndrome

Intervention

Drug:
• Dupilumab Prefilled Syringe
administration of dupilumab corresponding to dupilumab arm

Other:
• Placebo Prefilled Syringe
administration of placebo corresponding to placebo arm

Locations

Country	Name	City	State
France	Dermatologie Necker	Paris
France	Dermatology	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Toulouse	MedSharing

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The severity of the disease of the Netherton Area Severity Assessment score (NASA).	NASA score	Day 0 and week 16
Secondary	Clinical efficacy severity of pruritus and pain	NASA score	Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
Secondary	Presence of infections (adverse event)	Number of Bacterial or viral Skin infections	Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
Secondary	Quantity of dermocorticosteroids used between each visit will be evaluated by questioning the patient.	number of tubes multiplied by the weight of one tube	Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28
Secondary	QOL score	QOL score	Day 0, Week 16 and 28
Secondary	Skin inflammation	number of inflammation markers on biopsies	Day 0 and week 16
Secondary	Protease activity	number of protease markers on biopsies	Day 0 and week 16
Secondary	Microbiome qualitative and quantitative analysis	number and form of bacteria	Day 0 and week 16
Secondary	Transepidermal water loss (TEWL)	Measured by a Tewameter applied on a standardized area in the anterior aspect of the forearm,	Day 0 and Week 16
Secondary	Safety of dupilumab	Blood tests performed every month until Week 16 (liver and renal tests, total blood count)	Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28