Primary Objective- To assess efficacy and pharmacodynamic effects of topical omiganan BID Secondary Objectives- To assess safety and tolerability of topical omiganan BID
ID
Source
Brief title
Condition
- Skin and subcutaneous tissue disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacodynamic endpoints
Pharmacodynamic effects of Omiganan will be assessed at the time points
indicated in the Visit and Assessment Schedule (Table 1) by:
- Local (biopsy) biomarkers (IFN-alpha, IFN-gamma, IL 6, IL13, IL31, eotaxin3)
- Microbiome of skin lesions (in comparison to non-lesional skin)
- Bacterial colonization of skin lesions (S. aureus)
- Transepidermal water loss of lesional and non-lesional skin
- Transdermal analysis patch (TAP) biomarkers: IFN-gamma, IL-6, IL-10, IL-13,
IL-31, eotaxin3.
- Circulating cytokines (TARC, IFN-alpha, IFN-gamma, IL 6, IL13, IL31, eotaxin3)
- Thermography
Efficacy endpoints
Efficacy will be assessed at the time points indicated in the Visit and
Assessment Schedule (Table 1) by:
- Clinical assessment using SCORAD; EASI and IGA
- Patient-reported itch (daily NRS and weekly POEM)
- General clinical assessment
- Standardized total body clinical photography
- Diary for drug compliance and use of escape medication
- Partial / complete clearance of AD lesions
Secondary outcome
Tolerability / safety endpoints
Adverse events (AE) will be collected throughout the study, at every study
visit. Laboratory safety testing, 12-Lead ECGs and vital signs will be
performed and measured multiple times during the course the study according to
the Visit and Assessment Schedule.
Pharmacokinetic endpoints
Following PK samples will be analyzed:
- Day 28; Pre-dose, 10, 20, 30, 60, 120 and 180 minutes
Background summary
Atopic dermatitis (AD) is a chronic, pruritic, in*ammatory skin disease that
occurs frequently in children, but also affects many adults. Clinical features
of AD include skin dryness, erythema, oozing and crusting, and lichenification.
Pruritus is a hallmark of the condition and is the main driver of the high
disease burden for patients and their families.
Two major models currently exist to explain the pathogenesis of AD. The
predominant model describes AD as a result of impaired epidermal barrier
function due to intrinsic structural and functional abnormalities in the skin.
In this model, the disease evolves from the outside in, with an abnormal
epidermal barrier as the primary defect. The second and traditional model views
AD as primarily an immune function disorder in which Langerhans cells, T-cells,
and immune effector cells modulate an inflammatory response to environmental
factors.
Colonization of S. aureus is found in 90% of chronic AD patients versus 5% in
healthy individuals. Biofilm formation by AD-associated staphylococci almost
certainly plays a major role in the occlusion of sweat ducts and leads to
inflammation, pruritus and may therefor play a role in exacerbation. Endogenous
antimicrobial peptides are critical elements of the skin*s innate immunity. In
healthy skin, these peptides such as cathelicidins are induced upon
colonization or other external stimuli. However, in atopic skin cathelicidins
upregulation is abrogated by the presence of Th2 cytokines. This results in
lower levels of antimicrobial peptides, which could be a possible mechanism of
staphylococcal superinfection.
LL-37 and indolicidin are antimicrobial peptides that are members of the
cathelicidin family. Omiganan is a synthetic indolicidin analogue with
antimicrobial and immuno-modulatory activity. Recently it has been demonstrated
that enhanced LL-37 expression improves barrier function of the skin. Regarding
the mechanism of action, omiganan disrupts the cytoplasmic wall of
microorganisms, resulting in depolarization and cell death. Omiganan was
effective against a wide variety of bacteria and fungi, including S. aureus.
Immunomodulatory effects of omiganan were observed in a mouse model with
TPA-induced ear edema. To date, omiganan was assessed in various clinical
studies including patients with acne or rosacea where varying anti-inflammatory
activity of this compound could be demonstrated.
A previous study investigated the administration of 2.5% omiganan QD in
patients with mild to moderate atopic dermatitis on one target lesion. The
results of this trial showed statistical significant improvement of patient
reported morning itch and the local objective SCORAD compared to placebo. Since
the outcomes suggest dose dependency to a certain degree, we hypothesize that
administration of omiganan twice daily will lead to a more effective treatment
of mild to moderate AD.
This study is intended to assess the clinical efficacy and pharmacodynamics of
omiganan as a potential treatment for AD. Clinical efficacy by means of
clinical outcomes (i.e. clearance of the lesions, oSCORAD, EASI) and
sub-clinical parameters / biomarkers on the skin and systemic ones will be
assessed.
Study objective
Primary Objective
- To assess efficacy and pharmacodynamic effects of topical omiganan BID
Secondary Objectives
- To assess safety and tolerability of topical omiganan BID
Study design
A randomized, double-blind, vehicle controlled study to assess the efficacy,
pharmacodynamics (PD), safety/tolerability of omiganan BID in patients with
mild to moderate AD.
Intervention
Volunteers with AD will apply gel on all AD lesions bidaily for a period of 4
weeks. Based on randomization this gel is placebo (only vehicle), contains 1%,
1.75% or 2.5% Omiganan*5HCL.
Study burden and risks
The risks associated with the topical administration of CLS001 to humans has
been identified in over 2500 subjects in total in fourteen clinical trials
completed with topical applications of omiganan in formulations ranging from
0.5% to 3% in an aqueous gel and from 1% to 5% in an alcoholic solution for the
indications of various indications including treatment of the inflammatory
lesions of rosacea, treatment of acne and treatment of S. aureus in the nasal
carriage. Omiganan when applied topically to intact or abraded skin,
intranasally or at peripheral and central venous catheter sites appears to be
safe and well tolerated. In addition, omiganan was not detected in the plasma
of subjects after topical application to intact or abraded skin, to the nasal
mucosa or at peripheral catheter sites. The risk of topical application to a
very restricted lesional area can be considered minimal. Potential beneficial
effects on atopic dermatitis lesions are to be explored in this study.
Therefore, providing the protocol is adhered to, careful observation and
medical management will minimize any associated risk in this study.
1500 Liberty Ridge Drive, Suite 3000 -
Wayne, Pennsylvania 19087
US
1500 Liberty Ridge Drive, Suite 3000 -
Wayne, Pennsylvania 19087
US
Listed location countries
Age
Inclusion criteria
1. Male and female subjects with mild to moderate AD 18 to 65 years of age, inclusive. The health status is verified by absence of evidence of any clinical significant active or uncontrolled chronic disease other than AD following a detailed medical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, virology and urinalysis;
2. AD diagnosis confirmed;
3. Symptoms present for at least 1 year;
4. EASI between 7.1 - 50.0, inclusive at screening;
5. 2-20% body surface area (BSA) affected at screening;
6. Body mass index (BMI) between 18 and 35 kg/m2, inclusive, and with a minimum weight of 50 kg;
7. Able to participate and willing to give written informed consent and to comply with the study restrictions;
8. Subjects and their partners of childbearing potential must use effective contraception, for the duration of the study and for 3 months after the last dose.
Exclusion criteria
1. Any current and / or recurrent clinical significant skin condition other than AD;
2. Pregnant, a positive pregnancy test, intending to become pregnant, or breastfeeding;
3. Ongoing use of prohibited atopic dermatitis treatments. Washout periods prior to baseline (first dose of the study drug) are as follows:
a. Cyclosporine/oral steroids/azathioprine/mycophenolate mofetil/other systemic immunosuppressants: 4 weeks
b. Phototherapy: 3 weeks
c. Biologics: 5 half-lives of the drug
d. Topical calcineurin-inhibitors: 10 days;
4. Use of topical medication (prescription or over-the-counter [OTC]) within 14 days of study drug administration, or less than 5 half-lives (whichever is longer) in local treatment area;
5. Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks of enrollment;
6. Known hypersensitivity to the compound or excipients of the compound or known hypersensitivity to one or more different emollients;
7. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year;
8. Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening;
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 | EUCTR2016-003849-28-NL |
| CCMO | NL59314.056.16 |