AntiTNF-SN: Clinical Trial Using Humira in Netherton Syndrome

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT02113904

Collaborator

(none)

Enrollment

Location

Arm

43.8

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

N/A

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 :

Jan 27, 2014

Actual Primary Completion Date :

Dec 20, 2016

Actual Study Completion Date :

Sep 21, 2017

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Adalimumab

Drug: Adalimumab

6 injections (one every 15 days during 3 months)

Other Names:

Humira

Outcome Measures

Primary Outcome Measures

SN-EASI score and EASI score [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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Necker Enfants Malades hospital	Paris		France	75015

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Study Chair: Christine Bodemer, MD, PhD, : Department of Dermatology, Necker Enfants malades hospital, University Paris Descartes 149 rue de sèvres 75015 Paris, France