Clinical Trial Using Humira in Netherton Syndrome

NCT ID: NCT02113904

Last Updated: 2017-10-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-27
• Study Completion Date: 2017-09-21

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.

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

Conditions

Netherton Syndrome

Keywords

Netherton syndrome; Adalimumab; TNF-alpha; Orphan genetic syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Adalimumab

Group Type: EXPERIMENTAL

Adalimumab

Intervention Type: DRUG

6 injections (one every 15 days during 3 months)

Interventions

Adalimumab

6 injections (one every 15 days during 3 months)

Intervention Type: DRUG

Other Intervention Names

Humira

Eligibility 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

• Minimum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christine Bodemer, MD, PhD

Role: STUDY_CHAIR

: Department of Dermatology, Necker Enfants malades hospital, University Paris Descartes 149 rue de sèvres 75015 Paris, France

Locations

Necker Enfants Malades hospital

Paris, , France

Countries

France

Other Identifiers

2013-002205-54

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

P100150

Identifier Type: -

Identifier Source: org_study_id