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

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

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.

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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


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




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)



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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04244006


Contacts
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Contact: Nadège ALGANS 0561777204 ext +33 algans.n@chu-toulouse.fr
Contact: Helene TEXIER texier.h@chu-toulouse.fr

Locations
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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
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Principal Investigator: Juliette MAZEREEUW-HAUTIER Toulouse Hospital
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Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT04244006    
Other Study ID Numbers: RC31/19/0045
First Posted: January 28, 2020    Key Record Dates
Last Update Posted: September 5, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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