Main study:To evaluate the efficacy of dupilumab in patients with inflammatory subtypes of severe chronic hand eczema with an inadequate response or intolerance to alitretinoin and in patients with concomitant positive patch test results.Substudy:…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study:
Severity of hand eczema, measured with the proportion of patients reaching 75%
improvement on the Hand Eczema Severity Index (HECSI-75).This instrument is
being used in the standard care of patients with hand eczema.
The amount of positive patch test results compaired to baseline.
Substudy:
Difference in gene expression profile before and after treatment.
Secondary outcome
• health related quality of life.
• improvement in severity of hand eczema, assessed by the patient.
• improvement in severity of hand eczema, assessed by the photographic guide
for hand eczema.
• improvement in severity of hand eczema, assessed by the hand eczema severity
index (mean percentage change, HECSI-50, HECSI-90).
• work productivity and impairment.
• the safety and tolerability of treatment.
• treatment-related changes in the serum biomarkers.
• the effects of dupilumab treatment on histologic morphology.
• the effects of dupilumab treatment on the microbiome colonization profiles.
Background summary
Hand eczema is a common condition with a 1-year prevalence up to 10%.
Alitretinoin is the only approved systemic treatment for all clinical types of
hand eczema. However, it is less effective in non-hyperkeratotic forms, such as
the inflammatory subtypes of hand eczema. In our current clinical experience
with dupilumab, patients with atopic dermatitis and concomitant hand eczema
also have beneficial effects on hand eczema. Among these patients were also
patients who were refractory to alitretinoin and other off-label
immunosuppressive drugs.
Study objective
Main study:
To evaluate the efficacy of dupilumab in patients with inflammatory subtypes of
severe chronic hand eczema with an inadequate response or intolerance to
alitretinoin and in patients with concomitant positive patch test results.
Substudy:
To compare genomic changes due to dupilumab in active HE lesions and changes in
the HE transcriptome defined by gene expression differences between lesional
and non-lesional skin.
Study design
A randomized, double-blind, placebo-controlled proof of concept efficacy study,
set in a university dermatology clinic, tertiary referral center.
Intervention
Group I: dupilumab in starting dose of 600mg s.c. and subsequently 300mg s.c.
every two weeks.
Group II: placebo in starting dose of 600mg s.c. and subsequently 300mg s.c.
every two weeks.
The treatment period is 16 weeks.
Study burden and risks
Eligible patients will be recruited during routine clinical consultations in
the department of Dermatology of the UMCG. There is a total of 6 visits. The
screening comprises a short medical exam, disease severity assessment,
epicutaneous allergy test, serum test and for women also a pregnancy test.
Participants will be asked to fill out the questionnaires five times. Clinical
photographs will be taken at defined intervals. At every visit a short medical
exam will be performed and patients will be asked about possible side effects.
Extra biomarker laboratory measurements will be carried out, but these will be
carried out during the laboratory measurements that are routinely assessed in
treatment with dupilumab in AD patients. If patients participate in the
substudy, skin biopsies will be performed. This is a standard dermatological
procedure, performed on a daily base. It is a generally safe procedure with
minimal burden to the patient. Biopsies can be mainly associated with a small
risk of scarring, prolonged bleeding and/or infection. One extra visit is
needed to give patients consideration time before participation in the study.
Results of the trial can be related to the population of patients with severe
hand eczema.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-001561-32-NL |
| CCMO | NL71585.042.19 |