Biological Effects of LEO 43204 in Actinic Keratosis

NCT02600598 | Completed Phase 1

• 1 other identifier: LP0084-1228
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase I, single-centre, open label, within-subject comparison trial to explore the biological effects of LEO 43204 Gel, 0.037%, applied once daily for 3 consecutive days in patients with actinic keratosis on the upper extremity. The treatment area for each patient will be as defined as a contiguous area of 250 cm2 of skin on the upper extremity (including the dorsum manus) that contains a minimum of 5 AK lesions. Additionally there must be at least one AK lesion located in a non-treated area on the contralateral arm. All eligible subjects will receive LEO 43204 Gel, 0.037%, on the treatment area on Days 1, 2 and 3. Study medication application will be (sub)investigator applied. A total of 30 patients will be enrolled into this study (n=15 in each of the two groups). Patients will be divided into two groups with different biopsy schedules.

Conditions

Actinic Keratosis

Outcome Measures

Primary Outcomes (1)

• Number of CD3+ T lymphocytes assessed by immunohistochemistry in biopsies from AK lesions 56 days after first treatment.

  56 days

Secondary Outcomes (7)

• Number of infiltrating cells assessed by immunohistochemical staining

  8 weeks

• Expression of inflammatory and skin matrix modulation markers assessed by RNA expression and immunohistochemistry

  8 weeks

• Expression of ICAM-1 (marker of vascular endothelium activation) assessed by immunohistochemical staining as area of section with positive staining.

  8 weeks

• Expression of Ki-67 and K16 (markers of cell proliferation and differentiation) assessed by immunohistochemical staining as area of section with positive staining.

  8 weeks

• Expression of cleaved caspase-3 (apoptosis) assessed by immunohistochemical staining as area of section with positive staining

  8 weeks

Study Arms (2)

LEO 43204 Group A

EXPERIMENTAL

Group A - Experimental LEO 43204, applied once daily for 3 consecutive days in patients with actinic keratosis

Drug: LEO 43204 Gel, 0.037%

LEO 43204 Group B

EXPERIMENTAL

Group B - Experimental LEO 43204, applied once daily for 3 consecutive days in patients with actinic keratosis

Drug: LEO 43204 Gel, 0.037%

Interventions

LEO 43204 Gel, 0.037% DRUG

LEO 43204 Group A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Signed and dated informed consent has been obtained.
• \. Subjects with at least 5 non-keratotic, clinically typical, visible and discrete AK lesions within a contiguous 250 cm2 area (AK Treatment Area) on the upper extremity,
• \. Subjects with one additional AK lesion located on the contralateral arm.
• \. Subjects with an area of normal skin in close proximity to the AK Treatment Area or on the contralateral arm.
• \. Male and female subjects, 18 years or older.
• \. Agreement from the patient to allow photographs of the selected treatment area to be taken and used as part of the study data package
• \. Ability to follow study instructions and likely to complete all study requirements
• \. Female Subjects must be of either
• non-childbearing potential, i.e. post-menopausal or have a confirmed clinical history of sterility (e.g. the subject is without a uterus or has tubal litigation) or,
• child-bearing potential\* provided there is a confirmed negative pregnancy test prior to trial treatment to rule out pregnancy.
• Female subjects are considered of child-bearing potential unless they have had a hysterectomy or have undergone tubal litigation or have been post-menopausal for at least one year prior to first visit.
• \. Female subjects of child-bearing potential must be willing to use effective contraception at trial entry and until completion.
• Effective contraception is defined as follows:
• Abstinence (when this is in line with the preferred and usual life style of the subject).
• Vasectomised partner (given that the subject is monogamous).

You may not qualify if:

• \. Prior treatment with ingenol mebutate gel in the treatment area within the last 12 months.
• \. Previously assigned treatment in this clinical trial or previously participated in a clinical trial in the LEO 43204 programme (presently LP0084-68, LP0084-1013, LP0084-1014, LP0084-1015, LP0084-1148, LP0084-1077, LP0084-1193, LP0084-1194, LP0084-1195, LP0084-1196).
• \. Location of the selected treatment area within 5 cm of an incompletely healed wound or infected area of the skin (excl. study related biopsies) or within 5 cm of a suspected basal cell carcinoma (BCC) or SCC.
• \. History or evidence of skin conditions other than the study indication that would interfere with the histologically- or biomarker evaluation of the study medication (e.g. eczema, unstable psoriasis, xeroderma pigmentosum).
• \. Treatment area lesions that have an atypical clinical appearance (e.g. hypertrophic, hyperkeratotic, recalcitrant disease \[had cryosurgery on two previous occasions\] and/or cutaneous horns).
• \. Known sensitivity or allergy to any of the ingredients of LEO 43204 Gel (e.g. citric acid)
• \. Clinical diagnosis/history or evidence of any medical condition that would expose a subject to an undue risk of a significant AE or interfere with assessments of safety during the course of the study, as determined by Investigator clinical judgment.
• \. Anticipated need for in-patient hospitalisation or in-patient surgery during the study period. Note that cosmetic/therapeutic procedures are not excluded if they fall outside of the criteria detailed in the Prohibited Therapies or Medications (listed below).
• \. Anticipated excessive or prolonged exposure to ultraviolet light (e.g. sunlight) or use of tanning beds for the duration of the study
• \. Current participation in any other interventional clinical trial
• \. Subjects who have received treatment with any non-marketed drug product (i.e. an agent which has not yet been made available for clinical use following registration) within the last two months.
• \. Subjects known to be infected with Human Immunodeficiency Virus (HIV).
• \. Subject known or, in the opinion of the investigator, is unlikely to comply with the Clinical Study Protocol (e.g. alcoholism, drug dependency or psychotic state).
• \. Females who are pregnant, of child-bearing potential and wishing to become pregnant during the trial, or are breast feeding.
• \. Females of child-bearing potential with positive pregnancy test at \[screening or visit 1\].

Sponsors & Collaborators

• LEO Pharma: lead

Study Sites (2)

Beacon Clinical Research, LLC

Quincy, Massachusetts, 02169, United States

Location

Long Island Skin Cancer and Dermatology Surgery

Smithtown, New York, 11787, United States

Location

Related Links

• Clinical Trials at LEO Pharma

MeSH Terms

Conditions

Keratosis, Actinic

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Daniel Siegel, MD

  Long Island Skin Cancer and Dermatology Surgery

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2015
• First Posted: November 9, 2015
• Study Start: July 1, 2016
• Primary Completion: December 27, 2016
• Study Completion: January 16, 2017
• Last Updated: February 24, 2025

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)