Primary objective: • To assess efficacy of CLS003 in reduction of wart area after six weeks of treatment when applied to cutaneous warts (common or plantar)• To evaluate the activity of the ionic contra-viral therapy CLS003, in a HPV biomarker after…
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 CLS003 will be assessed at the time points indicated
in the Visit and
Assessment Schedule (Table 1) by
• Morphological wart assessment on-site;
• Wart size and morphology assessment by standardized clinical photography;
• HPV viral load assessment of target lesions by quantitative PCR including HPV
genotyping in swabs and biopsies.
• Percent reduction in wart area at Week 6 to baseline
• Percent reduction in wart area at follow-up Weeks 10 and 14 to baseline
• 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 0, 2,4,6, 10
and 14 to baseline
• Mean HPV viral load (nominal, natural log transformed, and natural log of
viral load per DNA copies)at treatment weeks and overall
• Percent clearance of warts
Secondary outcome
Tolerability / safety endpoints
Adverse events (AE) will be collected throughout the study, at every study
visit. Vital signs will be collected at baseline and weeks 1, 4, 6, 10 and 14.
Plasma digoxin levels will be determined by therapeutic drug monitoring (TDM)
at week 2, week 4 and week 6. ECGs will be performed at screening and week 14
(EOS).
Background summary
Cutanea Life Sciences (CLS) is investigating various formulations with digoxin
and furosemide as a potential treatment for HPV
infections of skin and other similar tissue. The anti-viral activity of digoxin
and furosemide has been demonstrated in several in-vitro
studies conducted by CLS. Both drugs prompted antiviral effects by
extracellular K+; these effects were most potent when digoxin
and furosemide were used in combination.
This new approach, described as Ionic Contra-Viral Therapy (ICVT), is suggested
to be most effective via local application. One
potential viral target of ICVT is human papillomavirus (HPV) in associated
cutaneous and mucosal lesions. While there are multiple
potential clinical indications, this first study will focus on cutaneous warts.
Current clinical treatments for HPV infections mainly involve lesion
destruction. The usual first line treatments are wart paints
containing salicylic acid and / or lactic acid and cryotherapy, usually with
liquid nitrogen. However, current available treatments are
considered unsatisfactory and there is an unmet need to develop drugs with
greater efficacy and specificity.
Specifically, the ionic properties of digoxin and furosemide were noted to
inhibit the K+ influx on which DNA viruses rely for
replication. These drugs interact with the cell membrane ion co-transporters
Na+/K+-ATPase and Na+-K+-2Cl- co-transporter-1. This
controlled depletion of cellular K+ has the potential to broaden the spectrum
of antiviral activity.
This study is intended to utilize an efficient biomarker and pharmacokinetic
study design to assess safety and to evaluate ICVT as a
potential treatment for HPV-associated conditions in a small group of healthy
subjects as a pilot study. Because clinical outcomes
(i.e. clearance of the lesion) often require lengthy treatment / observation
periods the study design will utilize measurements of HPV
viral load as a biomarker of anti-viral effect.
Study objective
Primary objective:
• To assess efficacy of CLS003 in reduction of wart area after six weeks of
treatment when applied to cutaneous warts (common or plantar)
• To evaluate the activity of the ionic contra-viral therapy CLS003, in a HPV
biomarker after six weeks of treatment, and after four and eight weeks of
post-treatment follow-up, when applied to cutaneous warts (common or plantar),
as assessed by:
o Changes from pretreatment in wart area
o Clinical assessments of the wart morphology
o Changes from pre-treatment in the exploratory HPV quantitative biomarker
• To evaluate the changes in wart dimensions and morphology relative to the
specific HPV genotypes, and HPV viral load at pre-treatment (baseline)
Secondary objective:
• To evaluate the safety and tolerability of CLS003 when applied to cutaneous
warts for up to six weeks
Study design
This is a A Phase 2, Randomized, Vehicle-Controlled, Double-Blind,
Proof-of-Concept Study to Evaluate Efficacy and Safety of Topical Ionic
Contra-viral Therapy (ICVT) Comprised of Digoxin and Furosemide in Cutaneous
Warts.
Intervention
Subjects will administer a gel containing a dose of 10-25mg per wart. De gel
will contain either 0.125% furosemide (w/w), 0,125% digoxin (w/w), a
combination of digoxin 0.125% (w/w) and furosemide 0.125% (w/w) or solely the
vehicle.
Study burden and risks
CLS003 has been investigated in a prior phase I study conducted in twelfth (12)
healthy volunteers with cutaneous warts. Subjects were treated on 7
consequetive days. Plasma levels of furosemide en digoxin were below the limit
of quantification, indicating that CLS iss only marginally absorbed. CLS was
well tolerated and no serious adverse events occured. The most common reported
treatment emergent adverse events were all mild in severity and included
headache, application site erythema and application site pruritus.
CLS003 seems to be a quite safe product and subtherapeutic doses will be
administered. Nevertheless, we have implemented the
following precautionary measures;
• Subjects who have any current and / or recurrent pathologically relevant skin
infections/illness in the treatment area other than common
warts (with the exception of herpes simplex virus labialis) are excluded from
study participation;
• Subjects who have any current uncontrolled infection will be excluded from
study participation;
• Subjects with a known sensitivity to any of the investigational product
ingredients, including digoxin and furosemide are excluded
from study participation;
Thus, in this study the subjects will only receive sub-therapeutic doses of
test product and the subjects will be screened thoroughly
prior to study enrolment.
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
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 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;;3.Fitzpatrick skin type I-II-III-IV;;4.Capable of tolerating treatment;;5.Free of clinical significant systemic or dermatologic disorder, which, in the opinion of the investigator, will interfere with the study results or increase the risk of Adverse Events;6. Have at least 2 (non-subungual) common warts or at least 2 (non-subungual) plantar warts on non-genital, non-facial skin of which at least 2 are 3mm in diameter in their longest dimensions on the plane of the skin ;7.If female of childbearing potential, have a negative urine pregnancy test at Screening/Day 1, 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);;8.Able to participate and willing to give written informed consent and to comply with the study restrictions;;9.Ability to communicate well with the investigator in the Dutch language;;10.Free of any clinical significant systemic or dermatologic disorder, which, in the opinion of the investigator, will interfere with the study results or increase the risk of Adverse Events;;11.Willing to refrain from using cosmetics or other topical products in the treatment area, or prohibited medications for the duration of the study;;12.Agree not to use any wart-removing product (prescription or over-the-counter) other than the study product 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.For women: a positive pregnancy test and/or nursing at screening or women who plan to become pregnant or are breastfeeding.;3.A positive test for drugs of abuse at screening;;4.History of alcohol or illicit drug abuse (alcohol abuse defined as alcohol consumption > 28 units/week);;5.Positive test results for Hepatitis B, Hepatitis C or HIV;;6.Have used salicylic acid or any other over-the-counter wart-removing product in the treatment area within 30 days prior to enrolment;;7.Have received cryotherapy in the treatment area within 60 days prior to enrolment;;8.Have required systemic intake of immunosuppressive or immunomodulatory medication (including oral or parenteral corticosteroids) within 30 days prior to enrolment 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 pathologically relevant skin infections in the treatment area other than common warts (with the exception of herpes simplex virus labialis);;10.Have a known sensitivity to any of the investigational product ingredients, including digoxin and furosemide;;11.Clinically relevant abnormal laboratory results, ECG, vital signs, or physical findings at screening that in the opinion of the investigator would interfere with the study objectives or compromise subject safety;;12.Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times in the past year;;13.Any psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol;;14.Not having a general practitioner;;15.Not willing to accept information transfer which concerns participation in the study, or information regarding health, like laboratory results, findings at anamnesis or physical examination and eventual adverse events to and from his general practitioner;;16.Not willing to give permission to have the general practitioner to be notified upon participation in this study;
Design
Recruitment
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-003688-39-NL |
| CCMO | NL50718.056.14 |