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

Phase II Clinical Trial Using Humira in Netherton Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Netherton Syndrome
• Intervention / Treatment: Drug: Adalimumab

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

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris
    • Paris, Paris, France, 75015
      • Necker Enfants Malades hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adalimumab	Drug: Adalimumab; 6 injections (one every 15 days during 3 months); Other Names: Humira

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SN-EASI score and EASI score	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	month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SN-EASI score and EASI score	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	at inclusion before treatment
SN-EASI score and EASI score	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	month 6
Number of participants with adverse events	To evaluate the safety of adalimumab for netherton syndrome patients	month 3
CDLQI and DLQI	To evaluate the quality of life of the patients	at inclusion before treatment
CDLQI and DLQI	To evaluate the quality of life of the patients	month 3
CDLQI and DLQI	To evaluate the quality of life of the patients	month 6
Improvement of pain	Visual scale from 0 to 10	month 3
Improvement of pruritus	Visual scale from 0 to 10	month 3
Hair growth	Visual scale from 1 to 4	month 3
Circulating inflammatory response (pro-inflammatory cytokines) cutaneous inflammatory response	Markers of inflammatory response before and after treatment	month 3
Circulating inflammatory response (pro-inflammatory cytokines) cutaneous inflammatory response	Markers of inflammatory response before and after treatment	month 6

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: URC-CIC Paris Descartes Necker Cochin
• Investigators: Study Chair: Christine Bodemer, MD, PhD, : Department of Dermatology, Necker Enfants malades hospital, University Paris Descartes 149 rue de sèvres 75015 Paris, France

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2014
• Primary Completion (Actual): December 20, 2016
• Study Completion (Actual): September 21, 2017

Study Registration Dates

• First Submitted: April 2, 2014
• First Submitted That Met QC Criteria: April 11, 2014
• First Posted (Estimated): April 15, 2014

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Adalimumab; TNF-alpha; Netherton syndrome; Orphan genetic syndrome
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Infant, Newborn, Diseases; Skin Diseases; Congenital Abnormalities; Abnormalities, Multiple; Skin Diseases, Genetic; Skin Abnormalities; Keratosis; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Netherton Syndrome; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Adalimumab
• Other Study ID Numbers: P100150; 2013-002205-54 (EudraCT Number)

Drug and device information, study documents

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