* To evaluate the safety and tolerability of CyPep-1 when applied on healthy skin for up to one week. * To evaluate the safety and tolerability of CyPep-1 when applied to cutaneous warts for up to four weeks.* To evaluate the activity of the CyPep-1…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacodynamic / efficacy endpoints
Pharmacodynamic effects of CyPep-1 will be assessed at the time points
indicated in the Visit and
Assessment Schedule (Table 1) by
o Changes in morphology on-site;
o Change in total wart count;
o HPV viral load assessment of target lesions by quantitative PCR including HPV
genotyping in swabs and biopsies;
o Absolute reduction in wart size (diameter and volume) at Week 4 as compared
to baseline, measured by calliper and 3D photography;
o Absolute reduction in wart size (diameter and volume) at follow-up (week 10
and 16) as compared to baseline, measured by calliper and 3D photography;
o Change in the HPV viral load (nominal, natural log transformed, and natural
log of viral load per DNA copies) as determined by qPCR at Weeks 1, 2,3,4, 10
and 16 as compared to baseline
o Mean HPV viral load (nominal, natural log transformed, and natural log of
viral load per DNA copies) at treatment weeks and overall
o Percent reduction and clearance of warts
o If considered applicable, cellular and immune response in biopsies (inlcuding
H&E, HPV E4, Ki67)
Pharmacokinetic endpoints
Following PK samples will be analyzed:
Part 2: Day 28 (EOT) to determine if there is systemic exposure to CyPep-1.
Tolerability / safety endpoints
Adverse events (AE) will be collected throughout the study, at every study
visit. Vital signs and ECGs will performed at several timepoints as represented
in the Visit and Assessment schedules (table 1).
Secondary outcome
Exploratory endpoints
o Changes in morphology
o Changes in morphology by optical coherence tomography
Background summary
Human papillomavirus (HPV) refers to a group of DNA viruses that can induce
neoplastic growth of human epithelial cells. In the skin, these neoplastic
tumors are commonly known as warts. Cutaneous wart diagnosis is generally based
on clinical examination, but it can also be determined by specific histological
criteria. Some warts persist for many years and untreated warts represent a
pool of HPV cross infection within the community. Many people find warts either
unsightly or painful and there is considerable social stigma associated with
visible warts. Current clinical treatments for HPV-induced warts mainly involve
mechanical or chemical destruction. The usual first line treatments are wart
paints containing salicylic acid and / or trichloroacetic acid and cryotherapy
with liquid nitrogen. However, current available treatments are considered
painful, unsatisfactory and there is an unmet need to develop drugs with
greater efficacy and specificity.
Normal mammalian cells are known for their asymmetric distribution of
electrostatically neutral zwitterionic phospholipids within their membrane
bilayer. Their outer membrane leaflets consist mainly of cholinophospholipids
with neutral polar head-groups, while the aminophospholipids with negatively
charged headgroups, such as phosphatidylethanolamine (PE) and
phosphatidylserine (PS) are mainly found in their inner membrane leaflets. This
asymmetrical lipid arrangement is thought to promote mechanical membrane
stability, whereby especially interactions between the PS on the inner leaflet
and skeletal proteins seem to entail membrane modulatory effects. In contrast,
neoplastic cells often overexpress PS in the outer leaflet of their cell
membranes, resulting in a slightly more negatively charged membrane than normal
cells. As such, the electrochemical differences between normal and tumor cells
represent a largely unexplored therapeutic opportunity.
Based on this observation, Cytovation has developed CyPep-1, a
chemically synthesized, positively charged peptide consisting of 27-D amino
acids. Cytovation is investigating various formulations with CyPep-1 as a
potential treatment for HPV infections of skin and other tissues. CyPep-1s mode
of action selectively targets- and lyses HPV-infected cells by inducing
pyroptosis (necrosis) of infected keratinocytes by removing the surrounding
cell membrane. This releases viral particles, potentially providing in-situ
immunization. The described mode of action of this broad-spectrum product has
been validated through extensive preclinical testing and applies to all HPV
strains.
This Phase 1 study is intended to explore the safety, tolerability,
pharmacodynamics and efficacy of topical CyPep-1 as a potential treatment for
HPV-associated conditions. Since this is a first-on-human study of a topical
formulation, the first subjects will be monitored more frequently in order to
establish the safety profile. Because clinical outcomes (i.e.
reduction/clearance of the lesion) often require lengthy treatment /
observation periods, the study design will primarily utilize clinical
measurements of wart dimensions, along with HPV viral load as a biomarker of
anti-viral effect.
Study objective
* To evaluate the safety and tolerability of CyPep-1 when applied on healthy
skin for up to one week.
* To evaluate the safety and tolerability of CyPep-1 when applied to cutaneous
warts for up to four weeks.
* To evaluate the activity of the CyPep-1, after four weeks of treatment, and
after six and twelve weeks of post-treatment follow-up, when applied to
cutaneous common warts, as assessed by:
o Changes from pretreatment in wart size
o Clinical assessments of the wart morphology
o Changes from pre-treatment in the HPV load
Study design
This study has a phase 1, randomized, vehicle-controlled, double-blind, single
center design to explore the safety, tolerability and pharmacodynamics (PD) of
topically applied CyPep-1 in otherwise healthy patients with cutaneous warts.
The study will entail two parts. Part 1 will follow a target area of 5x5 cm
healthy skin to study tolerability and safety of the formulation. During this
study part also a maximum of 3 common warts, preferably at the dorsal side of
the hand / finger(s), will be treated. Several assessments will be done to
determine pharmacodynamics and (possible) efficacy after a treatment period of
1 week.
Part 2 will evaluate the pharmacodynamics and efficacy of CyPep-1 after a
treatment period of 4 weeks. Study part 2 will commence after an interim
analysis, e.g. a blind data review, of study part 1 has been conducted.
Intervention
o CyPep-1 topical formulation 1% (w/w)
o Vehicle topical formulation (placebo)
Study burden and risks
The nonclinical studies to date conducted on CyPep-1 indicate that there were
no unexpected adverse events following administration to dogs, rats or
mini-pigs. The risks associated with the topical administration of CyPep-1 to
humans have not yet been identified in man. Due to the topical administration
of CyPep-1 only limited systemic exposure can be expected. To mitigate the risk
a dense monitoring period is implemented after administration in Part 1. In
general the risk can be evaluated as acceptable.
Møllendalsveien 65C
Bergen 5009
NO
Møllendalsveien 65C
Bergen 5009
NO
Listed location countries
Age
Inclusion criteria
1. Healthy subjects (male, non-pregnant female), 18 to 65 years of age, inclusive. (Healthy status is defined by absence of evidence of any clinical significant/uncontrolled 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 35 kg/m2, inclusive;
3. Free of clinically significant systemic or dermatologic disorders, which, in the opinion of the investigator, will interfere with the study results or increase the risk of Adverse Events;
4. Have at least 1 (non- peri / subungual) common wart on the, preferably, dorsal side of the hand /fingers which is 3-10 mm (inclusive) in diameter in its longest dimension on the plane of the skin;
5. If female of childbearing potential, have a negative urine pregnancy test at Screening/Day 0, and is willing to use effective contraception during the study (i.e. oral, implanted, injectable, IUD, diaphragm, condom, tubal ligation, abstinence, or are in a monogamous relationship with a partner who has had a vasectomy);
6. Able to participate and willing to give written informed consent and to comply with the study restrictions;
7. Ability to communicate well with the investigator in the Dutch language;
8. Willing to refrain from using cosmetics or other topical products in the treatment area for the duration of the study;
9. Agree not to use wart-removing products (prescription or over-the-counter) in the target area or prohibited medications other than the study medication during the course of the study.
Exclusion criteria
Eligible subjects must meet none of the following exclusion criteria:
1. Any clinically significant abnormality as determined by medical history taking and physical examinations obtained during the screening visit that in the opinion of the investigator would interfere with the study objectives or compromise subject safety;
2. Not willing to use effective (double barrier) contraception until at least 3 months after last study drug application;
3. For women: a positive pregnancy test and/or breastfeeding at screening or women who plan to become pregnant;
4. A positive test for drugs of abuse at screening;
5. History of alcohol or illicit drug abuse (alcohol abuse defined as alcohol consumption > 21 units/week);
6. Positive test results for Hepatitis B, Hepatitis C or HIV;
7. Have used salicylic acid or any other over-the-counter wart-removing product including cryo-therapy in the treatment area within 28 days prior to first study drug application;
8. Have required systemic intake of immunosuppressive or immunomodulatory medication (including oral or parenteral corticosteroids) within 60 days prior to first study drug application or during the course of the study. Routine use of inhaled or intranasal corticosteroids during the study is allowed;
9. Have any current and / or recurrent clinical significant skin infection in the treatment area other than common warts;
10. Have a known sensitivity to any of the investigational product ingredients;
11. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times in the past year;
12. Donation of blood or blood loss of >500 mL within 3 months prior to screening or donation of plasma within 14 days
13. Not having a general practitioner;
14. Not willing to give permission to have the general practitioner to be notified upon participation in this study;
15. Any condition that in the opinion of the investigator would complicate or compromise the study or the well-being of the subject.;Part 2 only:
16. Have treatment resistant / persistent warts as defined as one of the following:
a. More than 5 different failed treatments including topical formulations and cryotherapy
b. Longer than 6 years presence of the target wart
c. Having received active treatment in a clinical trial with an experimental drug for cutaneous warts.
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 | EUCTR2018-002733-38-NL |
| CCMO | NL67664.056.18 |