genital warts / vulva dysplasia
Conditions
Interventions
Investigational drug
- CLS003: topical formulation (gel) containing digoxin (0.125% w/w) and
furosemide (0.125%).
Comparative treatment
- Vehicle topical formulation (placebo)
During the treatment
digoxin/furosemide
HPV-induced
Immunocompromised
Sponsors
Cutanea Life Sciences
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: For enrollment of subjects the following criteria must be met: 1. Vulvar HSIL or AGW patients, >= 18 years of age, 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 the immunocompromised patient group(s): having an immunosuppressive disease or receiving immunosuppressive therapy for any reason including but not limited to; patients with auto-immune disease, HIV patients, transplantation patients 3. In case of genital warts: have at least 3 genital warts (only applicable for study part 1) 4. In case of vulvar HSIL: at least one lesion that can be accurately measured (using RECIST criteria) 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 for 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
Exclusion criteria: Eligible subjects must meet none of the following 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacodynamic / efficacy endpoints - For both cohorts: • Lesion (vulvar HSIL or wart) size reduction as absolute and percent reduction in lesion diameter as measured by caliper and 3D photography • Change in patient-reported outcomes (QoL and patient-reported clearance) • HPV viral load assessment (quantitative PCR including HPV genotyping in swabs and biopsies) • Change in the HPV viral load (nominal, natural log transformed, and natural log of viral load per DNA copies) as determined by qPCR in swabs and biopsies • Mean HPV viral load (nominal, natural log transformed, and natural log of viral load per DNA copies) in swabs and biopsies • Histology (regression of vulvar HSIL or AGWs, HPV genotyping) • Local immunity status (Histological changes in immune cells in the mucosa/submucosa) - For vulvar HSIL cohort • Vulvar HSIL, size and reduction in lesion size (clinical assessment of lesions by RECIST, absolute reduction in lesion size, lesion size reduction (percentage) as measured by caliper and 3D photograpy • Percentage clearance of vulvar HSIL lesions • Proportion of subjects with all vulvar HSIL lesions cleared • Histology (regression of high grade dysplasia to no dysplasia) • Histological recurrence (progression of no dysplasia to high grade dysplasia) in the Part 1 follow-up period - For genital wart cohort: • Wart size and reduction in wart size of the target wart (absolute reduction in lesion size, lesion size reduction (percentage)) as measured by caliper and 3D photography • Percentage clearance of genital warts • Proportion of subjects with all genital warts cleared • Clinical recurrence in the Part 1 follow-up period | — |
Secondary
| Measure | Time frame |
|---|---|
| Adverse events (AE) will be collected throughout the study, at every study visit. Laboratory safety testing, 12-Lead ECGs and vital signs will be performed and measured multiple times during the course the study according to the Visit and Assessment Schedule. Plasma digoxin levels will be determined by therapeutic drug monitoring (TDM) at the end week 3 (day 21) and 6 (day 42). Patients will fill in a daily questionnaire (numeric rating scale pain/itch) about local tolerance (e-diary). | — |
Countries
The Netherlands
Outcome results
None listed