Primary ObjectiveTo explore the pharmacodynamics effects of topically applied OMN ono Tape-stripped skin of healthy volunteerso Tape-stripped and IMQ-primed skin of healthy volunteerso Tape-stripped skin prior to IMQ applicationSecondary Objectives…
ID
Source
Brief title
Condition
- Skin and subcutaneous tissue disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacodynamic effects of this study will be assessed at the time points
indicated in the Visit and Assessment Schedule (Table 3) by:
- Local (biopsy) biomarkers ((including but not limited to IL-8, IFN-*, IFN-*,
IFN-*, MXA, MX1, IL-6, IL-10, CCL20 and HBD-2)
- Histology (HE)
- Immunohistochemistry (CD1a, HLADR, CD8+, CD4+, CD14+, CD11c)
- Transdermal Analysis Patch (IL-8, IFN-*, IL-6, IL-10, CCL20 and HBD-2)
- Perfusion by Laser speckle contrast imaging (LSCI)
- Colorimetric
- Clinical evaluation (erythema grading scale)
- Photography (total body imaging); erythema index
- Thermography
- Skin microbiome
Secondary outcome
Tolerability / safety endpoints
- Vital signs
- 12-leads ECGs
- Local tolerance (Visual Analogue Scale (NRS) pruritus and pain)
- Circulating cytokines (IFN-*, IFN-*)
Background summary
Omiganan (OMN) is a novel, synthetic, cationic peptide. OMN appears to have in
vitro activity against a wide variety of microorganisms such as gram-positive
and gram-negative bacteria and fungi [1]. Recent evidence and in vitro models
suggest that OMN also has pleiotropic effects regarding immune modulation.
Cationic peptides are believed to support antiviral immune responses via
enhancement of toll-like receptors (TLR) including TLR3, TLR7 and TLR9, and
RIG-1/Mda5 signalling. The activation of TLRs and RIG-1/Mda5 induces interferon
responses. Additionally, in vitro models indicate a strong induction of
interferon responses enhanced by TLR3, RIG-1/Mda5 stimulation. This interferon
response is strongly activated in the presence of a TLR 7 trigger, which also
suggests to investigate the combined application of OMN with a TLR 7 agonist in
humans. On the other hand, omiganan may exert immunosuppressive effects, as
evidenced by an omiganan-dependent inhibition of the release of certain
pro-inflammatory cytokines following in vitro innate immune challenges of
primary human immune cells.
The mechanism of action of imiquimod (IMQ) is based on the specific binding to
TLR-7 and TLR-8, thereby activating central transcription factors which induce
the secretion of pro-inflammatory cytokines including interferons, interleukins
and tumor necrosis factor alpha (TNF- a) which leads to inflammation and immune
activation.
In a recent study (CHDR1430 Part A), a challenge model to temporarily induce
local skin inflammation with IMQ (Aldara® cream) in healthy volunteers was
developed. The top-line results of this study showed mild to moderate
reversible skin inflammation in terms of erythema, perfusion and biopsy
biomarkers when 5mg IMQ was applied once daily under occlusion to tape stripped
skin for 2 days.
This healthy volunteer study has been designed based on the observed OMN
effects in in vitro studies in primary human immune cells (CHDR1426,
CHDR14522), and the observed IMQ effects on human skin in a recent clinical
(CHDR1430A). The study objectives are (1) to investigate the immunomodulatory
effects of topically applied OMN in furthermore untreated skin, (2) to
investigate immuno-suppressive effects of OMN on IMQ-induced inflammatory
responses of the skin, and (3) to study whether OMN enhances antiviral effects
in the skin induced by IMQ. Moreover, safety and tolerability will be assessed.
Study objective
Primary Objective
To explore the pharmacodynamics effects of topically applied OMN on
o Tape-stripped skin of healthy volunteers
o Tape-stripped and IMQ-primed skin of healthy volunteers
o Tape-stripped skin prior to IMQ application
Secondary Objectives
* To assess safety and tolerability of topically applied OMN in combination
with IMQ
Study design
Randomized, evaluator-blinded, vehicle-controlled, dose- ranging study.
Study burden and risks
OMN: The nonclinical studies conducted to date on omiganan indicate that there
were no unexpected adverse events following topical administration to rats. The
risks associated with the topical administration of omiganan to humans have
been identified in over 2500 subjects for the indications of various
indications including treatment of the inflammatory lesions of rosacea,
treatment of acne, treatment of atopic dermatitis 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.
IMQ: The risks associated with the topical application of IMQ have been
identified in healthy volunteers as well as patients with various indications
for treatment, such as BCC, AK and genital warts. Treatment appears to be safe,
reversible and reasonably tolerated, with local skin reactions including
erythema, oedema, vesicles, erosions/ulcerations, weeping/exudate,
flaking/scaling/dryness and scabbing/crusting as main side effect. Since
psoriasis exacerbations due to IMQ treatment have been described, psoriasis
patients as well as patients with other auto-immune diseases and skin
diseases are excluded to participate in this study to minimize potential
risk(s).
Previous in vitro experiments with the application of IMQ to OMN primed human
PBMCs led to an increase in antiviral biomarkers (IFN*, IFN*, IFN*). No human
data is available yet. Although systemic exposure is not expected with this
limited treatment area, circulating IFN*, IFN* and IFN* will be measured at
multiple time points. A dense visiting schedule will be used to monitor adverse
events closely.
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. Healthy male and female subjects, 18 to 45 years of age, inclusive. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, haematology, blood chemistry, and urinalysis.
2. Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and with a minimum weight of 50 kg.
3. Fitzpatrick skin type I-III (Caucasian).
4. 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.
5. Able to participate and willing to give written informed consent and to comply with the study restrictions.
Exclusion criteria
1. Any disease associated with immune system impairment, including auto-immune diseases, HIV and transplantation patients
2. Family history of psoriasis
3. History of pathological scar formation (keloid, hypertrophic scar)
4. Have any current and / or recurrent pathologically, clinical significant relevant skin condition.
5. Previous use of imiquimod/ resiquimod/ gardiquimod
6. Known hypersensitivity to the (non)investigational drug, comparative drug, drugs of the same class, or any of their excipients.
7. Hypersensitivity for dermatological marker at screening
8. Requirement of immunosuppressive or immunomodulatory medication within 30 days prior to enrollment or planned to use during the course of the study.
9. Use of topical medication (prescription or over-the-counter [OTC]) within 30 days of study drug administration, or less than 5 half-lives (whichever is longer) in local treatment area
10. Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks of enrollment.
11. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year.
12. Loss or donation of blood over 500 mL within three months prior to screening
13. Pregnant, a positive pregnancy test, intending to become pregnant, or breastfeeding
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 | EUCTR2016-004702-34-NL |
| CCMO | NL60037.056.16 |