Clinical trial NCT03861455: Efficacy and Safety of Dupilumab Chronic Hands Eczema Refractory to Highly Potent Topical Corticosteroids
Official title: DUPECZEMAIN : Double Blind Placebo-controlled Randomized Multicenter Study Assessing the Efficacy and Safety of Dupilumab in Moderate to Severe Chronic Hands Eczema Refractory to Highly Potent Topical Corticosteroids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hand Eczema
Keywords: Chronic Hand Eczema
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2019-03-04
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized 1:1 to receive dupilumab 300 mg every 2 weeks after a 600 mg-loading dose of dupilumab on day 0 or placebo.
Primary purpose: TREATMENT

Brief summary: Dupilumab has recently demonstrated high efficacy and good safety profile in the treatment of moderate-to-severe atopic dermatitis. There is a crucial need of developing new treatment options in Chronic hand eczema refractory to topical therapy. Investigators hypothesise that Dupilumab will also have high efficacy and good safety profile in the treatment of moderate to severe Chronic hand eczema refractory to highly potent topical corticosteroids.

Detailed description: Chronic hand eczema is a frequent chronic inflammatory skin disease which may have significant physical, psychological and social impact on daily activities, emotional and social life as well as work. In Chronic hand eczema, there is a close relationship between atopic dermatitis (that involves 70% of patients), sensitization to environmental antigens and irritant triggering factors. There are limited treatment options for Chronic hand eczema refractory to highly potent topical steroids. The only systemic treatment labelled in Chronic hand eczema, alitretinoin, is associated with moderate efficacy, high drop-out due to adverse events and it requires strict contraception measures in women of child bearing potential. Dupilumab has recently demonstrated high efficacy and good safety profile in the treatment of moderate-to-severe atopic dermatitis. There is a crucial need of developing new treatment options in Chronic hand eczema refractory to topical therapy. the investigators hypothesise that Dupilumab will also have high efficacy and good safety profile in the treatment of moderate to severe Chronic hand eczema refractory to highly potent topical corticosteroids.

Eligibility criteria: Inclusion Criteria:

* Patients affiliated to a social insurance protection regimen.
* Patients with moderate to severe chronic (\>6 months) hand eczema with an Investigator global assessment (IGA) of 3 or 4 (out of a scale of 0 to 4).
* Patients intolerant (according to the physician) or resistant to highly potent topical corticosteroids. Inadequate response (resistance) to highly potent topical corticosteroids is defined as a history of failure to achieve and maintain remission or a low disease activity state (comparable to an IGA score of 0 \[indicating clear\] to 2 \[indicating mild\]) despite treatment with a daily regimen of highly potent topical corticosteroids applied for 14 days or for the maximum duration recommended for highly potent topical corticosteroids.
* Patients who are able to understand the study procedures including the ability to complete patient-oriented questionnaires.
* Patients who are able to apply a stable dose of emollients within 7 days before the baseline visit.
* Patients who agree to sign the written informed consent.

Exclusion Criteria:

* Hypersensitivity to dupilumab or to any of its ingredients
* Patients under adult autonomy protection system
* Any other condition (e;g., psoriasis) on the hands that according to the investigator will impair the ability to evaluate treatment effect.
* Treatment with topical corticosteroids or topical calcineurin inhibitors within one week of baseline.
* Treatment with oral immunosuppressants (including cyclosporine, methotrexate, azathioprine, mycophenolate mofetil), alitretinoin or phototherapy within 4 weeks of baseline visit.
* Treatment with an investigational drug within 8 weeks (or 5 half-lives) of baseline.
* Active chronic infection requiring the use of a systemic antibiotic within 2 weeks before study start.
* Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g., tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis, aspergillosis) despite infection resolution; or unusually frequent, recurrent, or prolonged infections, per investigator judgment.
* History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening.
* Positive for hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody at the screening visit.
* Patients with known helminth infections.
* Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study. Women of childbearing potential who are sexually active and unwilling to use an adequate birth control method

Primary outcomes:
measure: severity score mTLSS (modified Total Lesion Symptom Score)
timeFrame: Week 16
Secondary outcomes:
measure: Evolution of pruritus
timeFrame: Week 16
measure: Evolution of pain
timeFrame: Week 16
measure: Improvement of quality of life
timeFrame: Week 16
measure: Improvement of quality of life by EQ-5D-5L
timeFrame: Week 16
measure: evolution of sleep loss
timeFrame: Week 16
measure: IGA - Clearance
timeFrame: Week 16
measure: PaGa - Clearance
timeFrame: Week 16
measure: Improvement of work productivity
timeFrame: Week 16
measure: Evolution of the Eczema Area and Severity Index (EASI)
timeFrame: Week 16
measure: Incidence of Treatment-Emergent Adverse Event
timeFrame: Week 16
measure: evolution of laboratory parameters - full blood count
timeFrame: Week 16
measure: evolution of laboratory parameters - transaminases
timeFrame: Week 16
measure: evolution of laboratory parameters - total immunoglobulin E
timeFrame: Week 16
measure: evolution of laboratory parameters - specific immunoglobulin E
timeFrame: Week 16
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Saint André Hospital
city: Montpellier
country: France
facility: Hôpital Saint Eloi
city: Pierre-Bénite
country: France
facility: CHU Lyon-Sud Département d'allergologie et d'immunologie clinique
city: Toulouse
country: France
facility: Larrey Hospital
Study officials:
affiliation: Lyon Sud Hospital
name: Marie Tauber
role: STUDY_DIRECTOR
References:
citation: Halioua B. [Hand eczema : disability and impact]. Ann Dermatol Venereol. 2014 Jun;141 Suppl 1:S111-6. doi: 10.1016/S0151-9638(14)70148-6. French.
citation: Cortesi PA, Scalone L, Belisari A, Bonamonte D, Cannavo SP, Cristaudo A, De Pita O, Gallo R, Giannetti A, Gola M, Pigatto PD, Mantovani LG. Cost and quality of life in patients with severe chronic hand eczema refractory to standard therapy with topical potent corticosteroids. Contact Dermatitis. 2014 Mar;70(3):158-68. doi: 10.1111/cod.12130. Epub 2013 Sep 19.
citation: Fowler JF, Graff O, Hamedani AG. A phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of alitretinoin (BAL4079) in the treatment of severe chronic hand eczema refractory to potent topical corticosteroid therapy. J Drugs Dermatol. 2014 Oct;13(10):1198-204.
citation: Blauvelt A, de Bruin-Weller M, Gooderham M, Cather JC, Weisman J, Pariser D, Simpson EL, Papp KA, Hong HC, Rubel D, Foley P, Prens E, Griffiths CEM, Etoh T, Pinto PH, Pujol RM, Szepietowski JC, Ettler K, Kemeny L, Zhu X, Akinlade B, Hultsch T, Mastey V, Gadkari A, Eckert L, Amin N, Graham NMH, Pirozzi G, Stahl N, Yancopoulos GD, Shumel B. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet. 2017 Jun 10;389(10086):2287-2303. doi: 10.1016/S0140-6736(17)31191-1. Epub 2017 May 4.
citation: Molin S, Merl J, Dietrich KA, Regauer M, Flaig M, Letule V, Saucke T, Herzinger T, Ruzicka T, Hauck SM. The hand eczema proteome: imbalance of epidermal barrier proteins. Br J Dermatol. 2015 Apr;172(4):994-1001. doi: 10.1111/bjd.13418. Epub 2015 Feb 26.