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

• ClinicalTrials.gov Identifier: NCT04244006
• Recruitment Status: Recruiting
• First Posted: January 28, 2020
• Last Update Posted: September 5, 2021
• Sponsor: University Hospital, Toulouse
• Collaborator: MedSharing
• Information provided by (Responsible Party): University Hospital, Toulouse

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Netherton Syndrome	Drug: Dupilumab Prefilled Syringe; Other: Placebo Prefilled Syringe	Phase 2; Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: one arm with dupilumab (2/3 of patients) and one arm with placebo (1/3 of patients)
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Dupilumab and placebo will be provided in identically matching 2 mL pre-filled syringes. To protect the blind, each treatment kit of 2 mL (dupilumab/placebo) glass pre-filled syringes will be prepared such that the treatments (dupilumab and its matching placebo) are identical and indistinguishable and will be labeled with a treatment kit number.
• Primary Purpose: Treatment
• Official Title: A Randomized Double-blinded Pilot Study of the Efficacy and Safety of Dupilumab Versus Placebo in Patients With Netherton Syndrome
• Actual Study Start Date: July 23, 2020
• Estimated Primary Completion Date: June 1, 2022
• Estimated Study Completion Date: June 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. The severity of the disease of the Netherton Area Severity Assessment score (NASA). [ Time Frame: Day 0 and week 16 ]
   NASA score

Secondary Outcome Measures :

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

Eligibility Criteria

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

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.

Contacts and Locations

Contacts

Contact: Nadège ALGANS; 0561777204 ext +33; algans.n@chu-toulouse.fr

Contact: Helene TEXIER; texier.h@chu-toulouse.fr

Locations

France

Dermatologie Necker; Not yet recruiting

Paris, France, 75015

Contact: tobecompleted

Principal Investigator: Christine Bodemer

Dermatology; Recruiting

Toulouse, France

Contact: Helene TEXIER texier.h@chu-toulouse.fr

Principal Investigator: Juliette MAZEREEUW-HAUTIER

Sponsors and Collaborators

University Hospital, Toulouse

MedSharing

Investigators

• Principal Investigator: Juliette MAZEREEUW-HAUTIER; Toulouse Hospital

More Information

• Responsible Party: University Hospital, Toulouse
• ClinicalTrials.gov Identifier: NCT04244006
• Other Study ID Numbers: RC31/19/0045
• First Posted: January 28, 2020
• Last Update Posted: September 5, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Netherton Syndrome; Syndrome; Disease; Pathologic Processes; Abnormalities, Multiple; Congenital Abnormalities; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Skin Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Keratosis; Skin Diseases