Dupilumab in adults with severe chronic hand eczema with an inadequate response or intolerance to alitretinoin: a randomized, double-blind, placebo-controlled proof of concept efficacy study

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 30

Inclusion Criteria

• Age >= 18 years and <= 75 years.
• Severe or very severe chronic hand eczema as defined by a Physician Global
Assessment (PGA) using a validated Photoguide.
• Inflammatory subtypes of hand eczema: recurrent vesicular hand eczema or
chronic fissured hand eczema.
• An inadequate response to topical corticosteroids within 6 months before
screening.
• A history of prior alitretinoin exposure and inadequate response or
intolerance to alitretinoin.
• Patients has also received standard skin care, including emollients and
barrier protection as appropriate, without significant improvement.
• Patients has avoided irritants and contact allergens, if identified, without
significant improvement.
• Women of childbearing potential are required to use a highly effective method
of birth control, prior to receiving study intervention, during the study and
for at least 10 weeks after receiving the last administration of study
intervention.
• A woman of childbearing potential must have a negative serum or urine
pregnancy test (β-human chorionic gonadotropin [β-hCG]) at screening and at
Week 0 prior to administration of study intervention;
• Agree not to receive a live virus or live bacterial vaccination during the
study, or within 12 weeks after the last administration of study intervention.
• Agree not to receive a BCG vaccination during the study, or within 12 months
after the last administration of study intervention.
• Be willing and able to adhere to the prohibitions and restrictions specified
in this protocol.
• Must sign an informed consent form (ICF) indicating that he or she
understands the purpose of and procedures required for the study, and is
willing to participate in the study.

Exclusion Criteria

• Other clinical subtypes of hand eczema, e.g. hyperkeratotic hand eczema, as
defined by the Danish Contact Dermatitis Group.
• Treatment with alitretinoin, systemic immunosuppressive medication or UV
radiation within the previous 4 weeks.
• Patients with predominantly atopic dermatitis, in whom the hands are also
involved, but no main concern. Patients with controlled atopic dermatitis, in
which the hands are mainly affected, are eligible for inclusion.
• Psoriasis of the hands.
• Active bacterial, fungal, or viral infection of the hands.
• Pregnant/lactating or planning to become pregnant during the study period.
• Current malignancy (other than successfully treated non-metastatic cutaneous
squamous cell or basal cell carcinoma and*or localized carcinoma in situ of the
cervix).
• Participant has known allergies, hypersensitivity, or intolerance to
dupilumab or its excipients: L-arginine hydrochloride, L-histidine, polysorbate
80, sodium acetate, acetic acid, sucrose, water for injections.
• Participants with active helminth and other parasitic infections.
• Patients infected with human immunodeficiency virus (HIV) (positive serology
for HIV antibody).
• Patients testing positive for hepatitis B virus (HBV) or hepatitis C (HCV)
infection.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Main study:<br /><br>Severity of hand eczema, measured with the proportion of patients reaching 75%<br /><br>improvement on the Hand Eczema Severity Index (HECSI-75).This instrument is<br /><br>being used in the standard care of patients with hand eczema.<br /><br>The amount of positive patch test results compaired to baseline.<br /><br><br /><br>Substudy:<br /><br>Difference in gene expression profile before and after treatment. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• health related quality of life.<br /><br>• improvement in severity of hand eczema, assessed by the patient.<br /><br>• improvement in severity of hand eczema, assessed by the photographic guide<br /><br>for hand eczema.<br /><br>• improvement in severity of hand eczema, assessed by the hand eczema severity<br /><br>index (mean percentage change, HECSI-50, HECSI-90).<br /><br>• work productivity and impairment.<br /><br>• the safety and tolerability of treatment.<br /><br>• treatment-related changes in the serum biomarkers.<br /><br>• the effects of dupilumab treatment on histologic morphology.<br /><br>• the effects of dupilumab treatment on the microbiome colonization profiles.</p><br>