Primary ObjectiveTo assess the efficacy of Gladskin Eczema Cream BID in patients with mild to moderate AD as assessed by EASI ScoreSecondary Objectives* To assess the pharmacodynamic effects of Gladskin Eczema Cream on the skin-microbiome, with…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Tolerability / safety endpoints
Adverse events (AE) will be collected throughout the study, at every study
visit.
Pharmacodynamic endpoints
Pharmacodynamic effects of Gladskin will be assessed at the time points
indicated in the Visit and Assessment Schedule (Table 1) by:
- Multispectral imaging (erythema and roughness of target lesion)
- Laser speckle contrast imaging (LSCI, blood flow of target lesion)
- Microbiome of skin lesions (of target lesion and non-lesional skin)
- Bacterial colonization of skin lesions (S. aureus cultures of target lesion
and non-lesional skin)
- Local (biopsy) biomarkers may comprise, but are not limited to: IL-13, IL-4,
IL-5, IL-33, TSLP, IL-31, IL-22, eotaxin
- Transepidermal water loss of lesional and non-lesional skin
Efficacy endpoints
Efficacy will be assessed at the time points indicated in the Visit and
Assessment Schedule (Table 1):
- Clinical assessment using oSCORAD; EASI, IGA
- Target lesion oSCORAD and Total Signs and Symptoms (TSS)
- Patient-reported itch (daily NRS by ediary(app) and POEM)
- Dermatology Life Quality Index (DLQI)
- Standardized total body clinical photography
- Electronic diary for medical device compliance and use of escape medication
Secondary outcome
N.A.
Background summary
The pathophysiology of AD is complex and still not completely understood.
Genetic susceptibility, environmental factors, epidermal barrier abnormalities,
immunological disturbances and dysbiosis of the skin microbiota all play a role
in the disease and the variability of these mechanisms may explain the
heterogeneous character of AD. It remains hard to discern which of these
mechanisms are primary events (causing AD), secondary events (resulting from
AD), or both (Weidinger et al., 2018).
Staphylococcus aureus is an important player regarding dysbiosis in AD.
Colonization with this pathogen and a lower general microbial diversity is
apparent in approximately 70-90% of the AD patients (Totte et al., 2016).
Several factors contribute to enhanced S. aureus adhesion to AD skin. After
adhesion S. aureus may cause or exacerbate inflammation by binding of its
superantigens (SAgs) to MHCII molecules which induces an excessive production
of T cell cytokines (Spaulding et al., 2013). In addition, SAgs are also
allergens and generate an IgE response (Geoghegan et al., 2018).
Based on the hypothesis that dysbiosis plays an important role in the
pathogenesis of AD the microbiome and especially S. aureus might be a target
for novel therapies (Geoghegan et al., 2018, Nakatsuji et al., 2017). A topical
treatment targeting the perturbed microbiome is Gladskin Eczema Cream. Gladskin
is a topical cream registered as medical device class I, with Staphefekt
SA.100, a recombinant chimeric endolysin, as active ingredient. Endolysins are
bacteria-killing enzymes that originate from bacteriophages. Gladskin
specifically targets Staphylococcus aureus, leaving the other bacteria
unharmed. It is currently on the market as medical device for skin conditions
with an infectious component, e.g. acne vulgaris, rosacea and atopic
dermatitis. Questionnaire studies, both prospective and retrospective, indicate
the potential for using Gladskin in patients with eczema. However, no
randomized controlled clinical study has been performed to explore the
potential of Gladskin as monotherapy in patients with mild to moderate atopic
dermatitis.
The objective of this study is to assess the efficacy and pharmacodynamic
effects of Gladskin after twice daily application in patients with mild to
moderate atopic dermatitis.
Study objective
Primary Objective
To assess the efficacy of Gladskin Eczema Cream BID in patients with mild to
moderate AD as assessed by EASI Score
Secondary Objectives
* To assess the pharmacodynamic effects of Gladskin Eczema Cream on the
skin-microbiome, with emphasis on Staphylococcus aureus
* To assess the clinical and pharmacodynamic effects of Gladskin Eczema Cream
as assessed by (oSCORAD, IGA, target lesion oSCORAD, TSS, 3D imaging, laser
speckle contrast imaging, TEWL, itch and biopsy biomarkers)
* To assess the safety and tolerability of Gladskin Eczema Cream
Study design
A randomized, double-blind, placebo controlled, single center study.
Intervention
Gladskin eczema cream
Study burden and risks
Gladskin eczema cream is registered as medical device class I with CE marking,
and over the counter available.
In vitro skin sensitisation and irritation tests showed that Gladskin eczema
cream is not considered to be irritant. No prediction could be made in respect
of its potential to cause eye irritation, therefore general instructions in
this study will include a warning to avoid spill of cream in the eyes, when
applied to the face.
In addition to the in vitro work, the medical device currently has 5 years of
marketing experience. Very few adverse events are reported by customers. The
most frequently reported adverse events are redness, worsening of disease,
burning sensation, itching, and swelling. During the application in clinical
trial for a period of 12 weeks no substantial safety issues were reported (De
Wit J. et al.). In general it can be concluded that Gladskin eczema cream is
well tolerated without substantial risks for the trial subject. The short
treatment period of 14 days and the visit schedule will enable to monitor
closely potential adverse events.
The invasive measurements in this study consist of small, 3mm, skin punch
biopsies. These will be limited to 3 skin biopsies in total.
In conclusion, we assess the risks associated with the medical device and
methods as low and acceptable for the patients to participate in the study.
Antonie van Leeuwenhoeklaan, building SR 9
Bilthoven 3721 MA
NL
Antonie van Leeuwenhoeklaan, building SR 9
Bilthoven 3721 MA
NL
Listed location countries
Age
Inclusion criteria
For enrollment of subjects the following criteria must be met:
1. Male and female subjects with mild to moderate AD (IGA 2 or 3) 18 to 55
years of age, inclusive. The health status is verified by absence of evidence
of any clinically significant active or uncontrolled chronic disease other than
AD following a detailed medical history and a complete physical examination
2. Diagnosed with AD according to the Hanifin criteria
3. EASI *4
4. Suitable target lesion defined as an eczema lesion of at least 1% BSA
(preferably the antecubital fossa) with at least mild erythema and mild
induration
5. *5% body surface area (BSA) affected at screening and baseline
6. Willing to not wash the target lesion 12 hours before every study visit
7. Willing to use microbiome friendly wash solution and refrain from other
products for washing from screening until end-of-study
8. Able to participate and willing to give written informed consent and to
comply with the study restrictions
9. Has sufficient Dutch language skills to be able to communicate well with the
Investigator, understand the informed consent and complete questionnaires and
e-diary.
Exclusion criteria
1. Any current and / or recurrent clinically significant skin condition other
than AD
2. Ongoing use of prohibited atopic dermatitis treatments. Washout periods
prior to baseline (first dose of the study medical device) are as follows:
a. Any topical medication (prescription or over-the-counter [OTC]): 14 days.
Continued use of emollients during wash-out is allowed.
b. Cyclosporine/oral steroids/azathioprine/mycophenolate mofetil/other systemic
AD treatments: 4 weeks
c. Phototherapy: 3 weeks
d. Biologics: 5 half-lives of the drug
e. Systemic antibiotics: 14 days
3. Tanning due to sunbathing, excessive sun exposure or a tanning booth within
3 weeks of enrolment
4. Known hypersensitivity to the compound or excipients of the compound
5. Pregnant, a positive pregnancy test, intending to become pregnant, or
breastfeeding;
6. Participation in an investigational drug or device study within 3 months
prior to screening or more than 4 times a year
7. Any (medical) condition that would, in the opinion of the investigator,
potentially compromise the safety or compliance of the patient or may preclude
the patient*s successful completion of the clinical trial.
8. Subject has a body temperature of >38°C at any visit;.
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
In other registers
| Register | ID |
|---|---|
| CCMO | NL71660.056.19 |
| OMON | NL-OMON24034 |