A Pilot Study of the Efficacy and Safety of Dupilumab Versus Placebo in Patients With Netherton Syndrome (NS-DUPI)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Netherton Syndrome
• Intervention / Treatment: Drug: Dupilumab Prefilled Syringe; Other: Placebo Prefilled Syringe

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Nadège Algans; Phone Number: +33 0561777204; Email: algans.n@chu-toulouse.fr
• Study Contact Backup: Name: Helene TEXIER; Email: texier.h@chu-toulouse.fr

Study Locations

• France
  • Paris, France, 75015
    • Not yet recruiting
    • Dermatologie Necker
    • Contact: tobecompleted
    • Principal Investigator: Christine Bodemer
  • Toulouse, France
    • Recruiting
    • Dermatology
    • Contact: Helene TEXIER; Email: texier.h@chu-toulouse.fr
    • Principal Investigator: Juliette Mazereeuw-Hautier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dupilumab; The patient will receive 2 doses at baseline and then 1 dose every 2 weeks (8 administrations in total) of Dupilumab 300 mg (syringe of 2 mL for subcutaneous administration).	Drug: Dupilumab Prefilled Syringe; administration of dupilumab corresponding to dupilumab arm
Placebo Comparator: Placebo; The patient will receive 2 doses at baseline and then 1 dose every 2 weeks (8 administrations in total) of placebo (syringe of 2 mL for subcutaneous administration)..	Other: Placebo Prefilled Syringe; administration of placebo corresponding to placebo arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The severity of the disease of the Netherton Area Severity Assessment score (NASA).	NASA score	Day 0 and week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
QOL score	QOL score	Day 0, Week 16 and 28
Skin inflammation	number of inflammation markers on biopsies	Day 0 and week 16
Protease activity	number of protease markers on biopsies	Day 0 and week 16
Microbiome qualitative and quantitative analysis	number and form of bacteria	Day 0 and week 16
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
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

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Collaborators: MedSharing
• Investigators: Principal Investigator: Juliette MAZEREEUW-HAUTIER, Toulouse Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: January 13, 2020
• First Submitted That Met QC Criteria: January 24, 2020
• First Posted (Actual): January 28, 2020

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Disease; Congenital Abnormalities; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Skin Diseases, Genetic; Skin Abnormalities; Abnormalities, Multiple; Keratosis; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Syndrome; Netherton Syndrome
• Other Study ID Numbers: RC31/19/0045

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No