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Clinical Trial Using Humira in Netherton Syndrome (AntiTNF-SN)

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ClinicalTrials.gov Identifier: NCT02113904
Recruitment Status : Completed
First Posted : April 15, 2014
Last Update Posted : October 18, 2017
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

The main objective of this studies therapeutic : to determine the effect of Adalimumab (HumiraR) on clinical inflammatory manifestations of patients with Netherton syndrome after 3 months of treatment , with a post treatment period follow-up of 3 months.

Second objectives are To evaluate the safety of Adalimumab in the context of NS To evaluate the improvement of the quality of life at 3 months To evaluate the improvement of pruritus and pain in the patients To study markers of inflammatory and allergy in NS prior and after treatment Benefit of the study An improvement by at least 20% of the cutaneous signs in these patients who suffer from a genetic incurable, chronic, painful and very afflicting disease would be of a great help for these patients. NS is a major source of social exclusion.

Risks They are inherent to the risks of biotherapies, especially for an anti-TNF therapy, they comprise a risk of infection. Cutaneous infections occur mainly during infancy, and we have therefore chosen to treat patients over 4 years of age in this study.

A close clinical surveillance will be set up (initially every week during the first month of treatment, then every month). This will represents a large number of visits but will provide a high level of security.

Benefits/risks ratio In the absence of curative treatment for these patients with a severe genetic skin disease, the benefits/risks ration clearly appears to be in favour of an expected benefit.


Condition or disease Intervention/treatment Phase
Netherton Syndrome Drug: Adalimumab Phase 2

Detailed Description:

Netherton syndrome (NS) is a rare (incidence is estimated at 1 in 100 000) but severe genetic skin disease characterized by scaly erythroderma at birth, abnormal hair and severe psoriasiform /atopic dermatitis-like lesions with high IgE levels and allergic manifestations. It has considerable impact on the quality of life of patients, as a result of inflammatory and painful flares, the chronicity of the lesions, severe growth retardation with definitive short stature.

NS is caused by loss of function SPINK5 mutations which lead to unregulated epidermal protease activity : kallikrein 5, kallikrein 7 and elastase proteases are found overactive following loss of inhibition. Secondly, KLK5 activates PAR-2 receptors at the keratinocyte surface leading to the activation of the NF-KB pathway and the release of different pro-inflammatory cytokines such TNF-alpha .

There is no specific treatment for NS. The different therapeutic attempts by Soriatane (acitretin) have worsen the skin inflammation and dryness. The use of topical calcineurin inhibitors (Tacrolimus) has sometimes improved skin inflammation but with an important systemic diffusion. The use of immune suppressive drugs in severe patients with NS followed in our labelized Centre (Cyclosporine, methotrexate, mycophenolate mofetil) have not brought a significant and durable improvement. So NS is a very distressing genodermatosis.

For these clinical and biological considerations, a benefit with anti TNF treatment could be expected and the evaluation of such treatment is justified in NS. The clinical case of an adult patient with severe NS, improved by anti-Tnf treatment has recently been published in the literature


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Clinical Trial Using Humira in Netherton Syndrome
Actual Study Start Date : January 27, 2014
Actual Primary Completion Date : December 20, 2016
Actual Study Completion Date : September 21, 2017


Arm Intervention/treatment
Experimental: Adalimumab Drug: Adalimumab
6 injections (one every 15 days during 3 months)
Other Name: Humira




Primary Outcome Measures :
  1. SN-EASI score and EASI score [ Time Frame: month 3 ]
    To evaluate the severity of specific netherthon syndrome clinical manifestation and the severity of atopic dermatitis before treatment, after three months of treatment, after a period of three months without treatment


Secondary Outcome Measures :
  1. SN-EASI score and EASI score [ Time Frame: at inclusion before treatment ]
    To evaluate the severity of specific netherthon syndrome clinical manifestation and the severity of atopic dermatitis before treatment, after three months of treatment, after a period of three months without treatment

  2. SN-EASI score and EASI score [ Time Frame: month 6 ]
    To evaluate the severity of specific netherthon syndrome clinical manifestation and the severity of atopic dermatitis before treatment, after three months of treatment, after a period of three months without treatment

  3. Number of participants with adverse events [ Time Frame: month 3 ]
    To evaluate the safety of adalimumab for netherton syndrome patients

  4. CDLQI and DLQI [ Time Frame: at inclusion before treatment ]
    To evaluate the quality of life of the patients

  5. CDLQI and DLQI [ Time Frame: month 3 ]
    To evaluate the quality of life of the patients

  6. CDLQI and DLQI [ Time Frame: month 6 ]
    To evaluate the quality of life of the patients

  7. Improvement of pain [ Time Frame: month 3 ]
    Visual scale from 0 to 10

  8. Improvement of pruritus [ Time Frame: month 3 ]
    Visual scale from 0 to 10

  9. Hair growth [ Time Frame: month 3 ]
    Visual scale from 1 to 4

  10. Circulating inflammatory response (pro-inflammatory cytokines) cutaneous inflammatory response [ Time Frame: month 3 ]
    Markers of inflammatory response before and after treatment

  11. Circulating inflammatory response (pro-inflammatory cytokines) cutaneous inflammatory response [ Time Frame: month 6 ]
    Markers of inflammatory response before and after treatment



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Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient over 4 years of age at the time of enrolment
  • Patient with a clinical, immuno-histochemical and/or molecular diagnosis confirmed
  • Vaccinations to date
  • Informed consent form signed by the patient and/or his parents (or the legal authority) if the patient is a child
  • Patient with social security coverage

Exclusion Criteria:

  • Ongoing severe infections
  • Well known allergy to one of Adalimumab ingredients
  • Allergy to xylocaine
  • Ongoing treatment to immunosuppressive drugs and biotherapies
  • History of malignancy
  • Heart, renal, haematological and/or confirmed hepatic involvement
  • Pregnant, or breastfeeding, patients
  • Anomalies of the standard balance sheet: neutropenia < 1000/mm3, polynucleose > 12 000 / mm3 - lymphopenia < 1000 / mm3 - anemia < 9g / 100ml - thrombocytopenia < 150 000 /mm3, thrombocytosis > 500 000/mm3 - transaminase > 3N

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): NCT02113904


Locations
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France
Necker Enfants Malades hospital
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Study Chair: Christine Bodemer, MD, PhD : Department of Dermatology, Necker Enfants malades hospital, University Paris Descartes 149 rue de sèvres 75015 Paris, France

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02113904     History of Changes
Other Study ID Numbers: P100150
2013-002205-54 ( EudraCT Number )
First Posted: April 15, 2014    Key Record Dates
Last Update Posted: October 18, 2017
Last Verified: October 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Netherton syndrome
Adalimumab
TNF-alpha
Orphan genetic syndrome
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
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents