Topical Ionic Contra-Viral Therapy in Actinic Keratosis

Study Overview
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Brief Summary
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To explore the pharmacodynamics and evaluate safety, tolerability and clinical efficacy of ICVT comprised of digoxin and furosemide (dual agent), digoxin (single agent), furosemide (single agent) in patients with AK.

Official Title
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A Phase 2, Randomized, Double Blind, Vehicle Controlled, Parallel Group Study to Explore the Efficacy, Pharmacodynamics and Safety of Topical Ionic Contra-Viral Therapy (ICVT) Comprised of Digoxin and Furosemide in Actinic Keratosis

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: ICVT Topical Gel
* Drug: Furosemide Topical Gel
* Drug: Digoxin Topical Gel
* Drug: Vehicle Topical Gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female subjects 18 years or older with verified condition of general good health (with exception of AK) Confirmed clinical AK diagnosis by dermatologist Subjects must have at least 2 facial fields of at least 25 cm² (but preferably >35 cm²) present at screening and baseline visit where more than 2 AK lesions are visible in each field (preferably the forehead, temple or cheek) Subjects must be able to participate and willing to give written informed consent and to comply with the study restrictions Subjects must be able to communicate well with the investigator in Dutch Subjects willing to refrain from using other topical products in the treatment area, or prohibited medication for the duration of the study Subjects must be willing to limit sun exposure of the involved skin to the extent vocationally possible 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: Have used or received any treatment for AK in the treatment area within 28 days prior to enrollment (including topical medications, immunosuppressive or immunomodulating agents, phototherapy, oral retinoids, or other therapies for AKs) Have any current pathologically relevant skin conditions in the field area other than AK (e.g. squamous cell carcinoma or basal cell carcinoma). Have a known hypersensitivity to any of the investigational product ingredients, including digoxin and furosemide. Current use of systemic digoxin or furosemide. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening or intention to donate blood or blood products during the study. If a woman of childbearing potential, pregnant, or breast-feeding, or planning to become pregnant during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ICVT<br>Digoxin and Furosemide (0.125%) | Drug: ICVT Topical Gel<br>* Digoxin and Furosemide (0.125%)<br>|
| Experimental: Furosemide<br>Furosemide (0.125%) | Drug: Furosemide Topical Gel<br>* Furosemide (0.125%)<br>|
| Experimental: Digoxin<br>Digoxin (0.125%) | Drug: Digoxin Topical Gel<br>* Digoxin (0.125%)<br>|
| Placebo Comparator: Placebo<br>Vehicle Gel | Drug: Vehicle Topical Gel<br>* Vehicle Gel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete clinical clearance (CCC) per field |  | Day 42 | 
| Change in AK-FAS (AK field assessment scale) | AK Grade 0-IV, the higher the number the more % area covered by AK | Day 42 | 
| Investigator global score (IGS) of each field | This is a 7 point scale from -2 (significantly worse) to +4 (completely cured), higher values represent a better outcome | Day 126 | 
| Evolution of one assigned target lesion in the field, assessed by dermoscopy | assessing erythema, scaling, pigmentation, and follicular plug | Day 126 | 
| Field morphology | Change in lesion count per field | Day 126 | 
| Standardized photography with Canfield VISIA or 2D photography and with Antera 3D camera |  | Day 126 | 
| Biopsy biomarker | Analysis will be prerformed for the following biomarker: IFN-a. IFN-g, Ki-67 | Day 126 | 
| Biopsy biomarker | Analysis will be prerformed for the following biomarker: IFN-g | Day 126 | 
| Biopsy biomarker | Analysis will be prerformed for the following biomarker: Ki-67 | Day 126 | 
| Biopsy biomarker | Analysis will be prerformed for the following biomarker: p53 | Day 126 | 
| Biopsy biomarker | Analysis will be prerformed for the following biomarker: MCM7(minichromosome maintenance protein 7) | Day 126 | 
| Biopsy biomarker | Analysis will be prerformed for the following biomarker:putrescene | Day 126 | 
| Biopsy biomarker | Analysis will be prerformed for the following biomarker: spermidine | Day 126 | 
| Biopsy biomarker | Analysis will be prerformed for the following biomarker: beta HPV types 5,8,15,20,24,38 | Day 126 | 
| Skin swab markers | Swab analysis will be performed for beta HPV types 5,8,15,20,24,38. | Day 126 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events collected throughout the study |  | Day 126 | 
| 12-Lead ECGs performed at Screening and End of Study | The following component will be assessed: Heart Rate (bpm | Day 126 | 
| 12-Lead ECGs performed at Screening and End of Study | The following component will be assessed: PR | Day 126 | 
| 12-Lead ECGs performed at Screening and End of Study | The following component will be assessed: QRS | Day 126 | 
| 12-Lead ECGs performed at Screening and End of Study | The following component will be assessed: QT | Day 126 | 
| 12-Lead ECGs performed at Screening and End of Study | The following component will be assessed: QTcB | Day 126 | 
| 12-Lead ECGs performed at Screening and End of Study | The following component will be assessed: QTcF | Day 126 | 
| Vital Signs performed at Screening and End of Study | The following will be assessed: Pulse Rate (bpm) | Day 42 | 
| Vital Signs performed at Screening and End of Study | The following will be assessed: Systolic blood pressure (mmHg) | Day 42 | 
| Vital Signs performed at Screening and End of Study | The following will be assessed: Diastolic blood pressure (mmHg) | Day 42 | 
| Vital Signs performed at Screening and End of Study | The following will be assessed: Temperature ( ̊ C) | Day 42 | 
| Patient diary on treatment application compliance, local tolerance and selfies photo |  | Day 42 |