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

Primary Purpose

Netherton Syndrome

Status

Recruiting

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Dupilumab Prefilled Syringe

Placebo Prefilled Syringe

About this trial

This is an interventional treatment trial for Netherton Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Dermatologie Necker
DermatologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Dupilumab

Placebo

Arm Description

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).

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)..

Outcomes

Primary Outcome Measures

The severity of the disease of the Netherton Area Severity Assessment score (NASA).

NASA score

Secondary Outcome Measures

Clinical efficacy severity of pruritus and pain

NASA score

Presence of infections (adverse event)

Number of Bacterial or viral Skin infections

Quantity of dermocorticosteroids used between each visit will be evaluated by questioning the patient.

number of tubes multiplied by the weight of one tube

QOL score

Skin inflammation

number of inflammation markers on biopsies

Protease activity

number of protease markers on biopsies

Microbiome qualitative and quantitative analysis

number and form of bacteria

Transepidermal water loss (TEWL)

Measured by a Tewameter applied on a standardized area in the anterior aspect of the forearm,

Safety of dupilumab

Blood tests performed every month until Week 16 (liver and renal tests, total blood count)

Full Information

NCT ID

NCT04244006

First Posted

January 13, 2020

Last Updated

August 22, 2023

Sponsor

University Hospital, Toulouse

Collaborators

MedSharing

1. Study Identification

Unique Protocol Identification Number

NCT04244006

Brief Title

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

Acronym

NS-DUPI

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

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 23, 2020 (Actual)

Primary Completion Date

June 1, 2024 (Anticipated)

Study Completion Date

June 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Toulouse

Collaborators

MedSharing

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Netherton Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Model Description

one arm with dupilumab (2/3 of patients) and one arm with placebo (1/3 of patients)

Masking

ParticipantCare ProviderInvestigator

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.

Allocation

Randomized

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Dupilumab

Arm Type

Experimental

Arm Description

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).

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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)..

Intervention Type

Drug

Intervention Name(s)

Dupilumab Prefilled Syringe

Intervention Description

administration of dupilumab corresponding to dupilumab arm

Intervention Type

Other

Intervention Name(s)

Placebo Prefilled Syringe

Intervention Description

administration of placebo corresponding to placebo arm

Primary Outcome Measure Information:

Title

The severity of the disease of the Netherton Area Severity Assessment score (NASA).

Description

NASA score

Time Frame

Day 0 and week 16

Secondary Outcome Measure Information:

Title

Clinical efficacy severity of pruritus and pain

Description

NASA score

Time Frame

Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28

Title

Presence of infections (adverse event)

Description

Number of Bacterial or viral Skin infections

Time Frame

Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28

Title

Quantity of dermocorticosteroids used between each visit will be evaluated by questioning the patient.

Description

number of tubes multiplied by the weight of one tube

Time Frame

Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28

Title

QOL score

Description

QOL score

Time Frame

Day 0, Week 16 and 28

Title

Skin inflammation

Description

number of inflammation markers on biopsies

Time Frame

Day 0 and week 16

Title

Protease activity

Description

number of protease markers on biopsies

Time Frame

Day 0 and week 16

Title

Microbiome qualitative and quantitative analysis

Description

number and form of bacteria

Time Frame

Day 0 and week 16

Title

Transepidermal water loss (TEWL)

Description

Measured by a Tewameter applied on a standardized area in the anterior aspect of the forearm,

Time Frame

Day 0 and Week 16

Title

Safety of dupilumab

Description

Blood tests performed every month until Week 16 (liver and renal tests, total blood count)

Time Frame

Day 0, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 28

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Nadège ALGANS

Phone

0561777204

Ext

+33

algans.n@chu-toulouse.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Helene TEXIER

texier.h@chu-toulouse.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Juliette MAZEREEUW-HAUTIER

Organizational Affiliation

Toulouse Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dermatologie Necker

City

Paris

ZIP/Postal Code

75015

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

tobecompleted

First Name & Middle Initial & Last Name & Degree

Christine Bodemer

Facility Name

Dermatology

City

Toulouse

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Helene TEXIER

texier.h@chu-toulouse.fr

First Name & Middle Initial & Last Name & Degree

Juliette MAZEREEUW-HAUTIER

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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