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

Study Overview

• Status: Terminated
• Conditions: HPV-Induced Genital Lesions
• Intervention / Treatment: Drug: Vehicle; Drug: CLS003

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands
    • LUMC/Centre for Human Drug Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CLS003; Digoxin and Furosemide topical formulation	Drug: CLS003; CLS003
Placebo Comparator: Vehicle; Inactive vehicle	Drug: Vehicle; Vehicle

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Maruho Co., Ltd.
• Investigators: Principal Investigator: J. (Koos) Burggraaf, MD, PhD, Centre for Human Drug Research

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2017
• Primary Completion (Actual): October 30, 2018
• Study Completion (Actual): October 30, 2018

Study Registration Dates

• First Submitted: October 30, 2017
• First Submitted That Met QC Criteria: November 6, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Actual): March 20, 2019
• Last Update Submitted That Met QC Criteria: March 18, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: HPV; Digoxin; Furosemide; Vulvar HSIL
• Other Study ID Numbers: CLS003-CO-PR-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes