Clinical Trial Using Humira in Netherton Syndrome

Netherton Syndrome Clinical Trial

— AntiTNF-SN  

Official title:

Phase II Clinical Trial Using Humira in Netherton Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02113904
• Other study ID #: P100150
• Secondary ID: 2013-002205-54
• Status: Completed
• Phase: Phase 2
• First received: April 2, 2014
• Last updated: October 16, 2017
• Start date: January 27, 2014
• Est. completion date: September 21, 2017

Study information

• Verified date: October 2017
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: September 21, 2017
• Est. primary completion date: December 20, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Netherton Syndrome
• Syndrome

Intervention

Drug:
• Adalimumab
6 injections (one every 15 days during 3 months)

Locations

Country	Name	City	State
France	Necker Enfants Malades hospital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

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