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

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

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

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.

Inclusion Criteria:

1. 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.
2. 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
3. In case of genital warts patient group(s): have at least 3 genital warts (only applicable to Study Part 1)
4. 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)
5. 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)
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 other topical products in the treatment area, or prohibited medications for the duration of the study

Exclusion Criteria:

1. 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
2. Have used or received any topical genital wart treatment, cryotherapy, electrocoagulation, surgery in the treatment area within 28 days prior to enrolment
3. Have used or received any topical vulvar HSIL treatment, laser therapy or surgery in the treatment area within 28 days prior to enrolment
4. 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)
5. Have a known sensitivity to any of the investigational product ingredients, including digoxin and furosemide
6. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times in the past year
7. Loss or donation of blood over 500 mL within three months prior to screening.