ICVT in HPV-induced Genital Lesions of Immunocompromised and Immunocompetent Patients

Study Overview
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Brief Summary
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This study is intended to explore and evaluate the pharmacodynamics and clinical efficacy of the ionic contra-viral therapy CLS003 in immunocompromised and immunocompetent patients with benign and premalignant HPV-induced genital lesions

Detailed Description
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This study is intended to explore clinical efficacy and safety/tolerability of ICVT as a potential treatment for benign and premalignant HPV-induced genital lesions in immunocompetent and immunosuppressed patients. This includes 3 different patient populations: i) immunocompetent patients with anogenital warts (AGWs), ii) immunocompromised patients with anogenital warts and iii) immunocompromised patients with vulvar high grade squamous intraepithelial neoplasia (HSIL), formerly referred to as usual type vulvar intraepithelial neoplasia (uVIN). Since digoxin / furosemide ICVT's mode of action is in part independent of the immune system and directly targeted to eradicate the causative HPV, we hypothesize this therapy to be of value in this specific group of individuals.

Official Title
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A Phase 2, Randomized, Vehicle-controlled, Double-blind Study to Explore the Efficacy, Pharmacodynamics and Safety of Topical Ionic Contra-viral Therapy (ICVT) Comprised of Digoxin and Furosemide in HPV-induced Genital Lesions of Immunocompromised and Immunocompetent Patients

Conditions
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HPV-Induced Genital Lesions

Intervention / Treatment
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* Drug: CLS003
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years in general, stable good health (with the exception of the immunocompromised disorder) as per judgment of the investigator based upon the results of a medical history, physical examination, ECG, chemistry, hematology. In case of immunocompromised patients including but not limited to; patients receiving immunosuppressive therapy for any reason, patients with auto-immune disease, HIV patients, transplantation patients In case of genital warts patient group(s): have at least 3 genital warts (only applicable to Study Part 1) In case of vulvar HSIL: at least one lesion that can be accurately measured in at least one dimension with longest diameter ≥ 20 mm OR in 2 perpendicular dimensions that when multiplied together give a surface area ≥ 120 mm² (only applicable to Study Part 1) If female of childbearing potential, have a negative urine pregnancy test at Screening and Day 0, and is willing to use effective contraception during the study and 3 months afterwards (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) Able to participate and willing to give written informed consent and to comply with the study restrictions Ability to communicate well with the investigator in the Dutch language Willing to refrain from using other topical products in the treatment area, or prohibited medications for the duration of the study Exclusion Criteria: Significant, uncontrolled or unstable disease in any organ system as per judgment of the investigator (regardless of association with the immunosuppressing disorder/therapy), including but not limited to: psychiatric, neurologic, cardiovascular, pulmonary, gastrointestinal, hepatic, renal, endocrine, hematologic or respiratory disease Have used or received any topical genital wart treatment, cryotherapy, electrocoagulation, surgery in the treatment area within 28 days prior to enrolment Have used or received any topical vulvar HSIL treatment, laser therapy or surgery in the treatment area within 28 days prior to enrolment Have any current relevant skin infections in the treatment area other than genital warts (inclusively, but not limited to atopic dermatitis, lichen sclerosis, lichen planus or psoriasis) Have a known sensitivity to any of the investigational product ingredients, including digoxin and furosemide Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times in the past year Loss or donation of blood over 500 mL within three months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: A total of 48 subjects are planned to be enrolled within one of the following three groups: a.) Immunocompetent patients with anogenital warts, b.) Immunocompromised with anogenital warts and c.) Immunocompromised with vulvar HSIL [3:1, active/vehicle]. Eligible subjects may enroll in an (up to) 8-week open-label Part 2 of study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CLS003<br>Digoxin and Furosemide topical formulation | Drug: CLS003<br>* CLS003<br>|
| Placebo Comparator: Vehicle<br>Inactive vehicle | Drug: Vehicle<br>* Vehicle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lesion (vulvar HSIL or wart) size reduction |  | Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study) | 
| Change in patient-reported outcomes |  | Through study completion, up to 20 weeks | 
| HPV viral load assessment |  | Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study) | 
| Change in the HPV viral load |  | Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study) | 
| Mean HPV viral load |  | Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study) | 
| Histology (regression of vulvar HSIL or AGWs to no dysplasia, HPV genotyping) |  | Day 0, 42, 126, (Part 1 of study), Day 56 (Part 2 of study) | 
| Local immunity status |  | Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study) | 
| Percentage clearance of vulvar HSIL lesions | For vulvar HSIL cohort | Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study) | 
| Proportion of patients with all vulvar HSIL lesions cleared | For vulvar HSIL cohort | Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study) | 
| Histology (regression of vulvar HSIL to no dysplasia) | For vulvar HSIL cohort | Day 0, 42, 126, (Part 1 of study), Day 56 (Part 2 of study) | 
| Histological recurrence in the Part 1 follow-up period | For vulvar HSIL cohort | Day 84, 126 | 
| Percentage clearance of genital warts | For genital wart cohort | Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study) | 
| Proportion of patients with all genital warts cleared | For genital wart cohort | Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study) | 
| Clinical recurrence in the Part 1 follow-up period | For genital wart cohort | Day 84, 126 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event collection to assess safety/tolerability of CLS003 |  | Day 0, 21, 42, 84, 126, (Part 1 of study), Day 0, 28, 56, 140 (Part 2 of study), and as volunteered by patient | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV, Digoxin, Furosemide, Vulvar HSIL