Primary Objective• To explore the pharmacodynamic effects of topically applied omiganan • To explore the treatment effect of omiganan compared to placebo in uVIN patients Secondary Objectives• To assess safety and tolerability • To explore the…
ID
Source
Brief title
Condition
- Vulvovaginal disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To measure the pharmacodynamic effect of topical omiganan on uVIN lesions
Secondary outcome
- To assess the safety and tolerability of Omiganan in uVIN patients
- To research the pharmacokinetics of Omiganan
Background summary
Usual type vulvar intraepithelial neoplasia (uVIN) is a human papillomavirus
(HPV)-induced premalignant skin disorder affecting the vulvar skin. The
incidence is increasing, especially in younger women. The majority of the
affected individuals have symptoms like itching, burning, dyspareunia, and
discolouration of the vulvar skin which may take on a warty appearance.
Standard treatment consists of surgery or laser treatment that can be
mutilating and causing physical and psychological problems. In addition, after
these treatments the risk of recurrence may be as high as 40-50%. Therefore,
there is need for topical treatments that women can apply at home and are
effective in treating uVIN without significant toxicity and without the need
for potentially mutilating surgery.
Endogenous antimicrobial peptides are critical elements of the endothelial
innate immunity. In healthy skin, these peptides such as cathelicidins are
induced upon colonization or other external stimuli. Omiganan is a synthetic
indolicidin analogue with antimicrobial and immuno-modulatory activity that is
hypothesized to effect HPV-mediated lesions on skin and other epithelia such as
the vaginal mucosa. Omiganan has been shown to have inhibitory effects against
HPV and it exhibited direct inhibitory effects in IL-8, MCP-1 and IL-10 in
vitro. Furthermore, immunomodulation mediated by TLRs was demonstrated since
omiganan inhibited IL-10, IL-6, IL-8 and TNF-α in a concentration-dependent
manner, as well as IL-1b.
CLS001 is a topical gel containing omiganan pentahydrochloride. In clinical
studies completed to date (seventeen trials with various formulations) in over
2500 subjects, topical administration of omiganan appears to be safe and well
tolerated. The majority of the adverse events that occurred in the clinical
trials were mild and resolved without treatment.
Due to the immunomodulatory activity of omiganan and its apparent anti-viral
activity, we hypothesize that omiganan is a potential new treatment for uVIN.
This study is intended to assess the pharmacodynamics of omiganan as a
potential treatment for uVIN. Furthermore, exploratory efficacy by means of
clinical outcomes (i.e. clearance of the lesions), time to recurrence and
sub-clinical parameters / biomarkers will be assessed.
Study objective
Primary Objective
• To explore the pharmacodynamic effects of topically applied omiganan
• To explore the treatment effect of omiganan compared to placebo in uVIN
patients
Secondary Objectives
• To assess safety and tolerability
• To explore the pharmacokinetics of omiganan
Study design
Part 1 is a phase 2 randomized, double-blind, parallel group study. Eligible
patients will be randomized in two treatment arms: topical 2.5% omiganan gel or
placebo for 12 weeks, with a ratio of 8:4 respectively . Per subject one or
more uVIN lesions will be treated. All patients that complete part 1 can be
enrolled in Part 2 of the trial with an open label, compassionate use of
topical 2.5% omiganan gel QD for up to 3 months.
Intervention
Patients will use 2.5% omiganan gel once daily on the VIN lesions
Study burden and risks
not applicable
656 Swedesford Road Suite 320 320
Pennsylvania 19087 Wayne
US
656 Swedesford Road Suite 320 320
Pennsylvania 19087 Wayne
US
Listed location countries
Age
Inclusion criteria
1. Women >= 18 years
2. Biopsy proven uVIN, biopsies to have been taken within the last three months
3. Written informed consent to participate in the trial
4. At least one lesion that can be accurately measured (using RECIST criteria)
o in at least one dimension with longest diameter >= 20mm
o OR in two perpendicular dimensions that when multiplied together give a surface area of greater than 120mm2 (e.g. 15mm x 8mm or 12mm x 10mm)
Exclusion criteria
1. Has any concomitant disease or significant medical conditions 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.
2. Clinically significant abnormalities, as judged by the Investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis) or ECG. In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects.
3. Indication of a current active infectious disease of the vulva, other than HPV
4. Pregnant, breast feeding or trying to conceive
5. Active treatment for uVIN within the previous eight weeks
6. Patients receiving immunosuppressive therapy
7. HIV positive or transplant patients
8. Any condition that in the opinion of the investigator could interfere with the conduct of the study
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 | EUCTR2015-002724-16-NL |
| CCMO | NL54315.056.15 |