A Study of Increasing Strengths, Safety and Efficacy of Two Formulas of LEO 43204 on the Face or the Chest in Patients With Actinic Keratosis

Safety and Efficacy of Escalating Doses of Two LEO 43204 Formulations Applied Once Daily for Two Consecutive Days on Full Face or Approximately 250 cm2 (40 in2) on the Chest in Subjects With Actinic Keratosis

Part 1:

To identify Maximum Tolerated Dose (MTD) levels of two formulations of LEO 43204 after once daily treatment for two consecutive days

Part 2:

To evaluate efficacy of two formulations of LEO 43204 in two doses after once daily treatment for two consecutive days compared to vehicle formulations

Study Overview

• Status: Completed
• Conditions: Actinic Keratosis
• Intervention / Treatment: Drug: LEO 43204 Formulation 1; Drug: LEO 43204 Formulation 2; Drug: LEO 43204 Formulation 1 Dose X; Drug: LEO 43204 Formulation 1 Dose Y; Drug: LEO 43204 Formulation 2 Dose XX; Drug: LEO 43204 Formulation 2 Dose YY; Drug: Placebo Formulation 1; Drug: Placebo Formulation 2

• Study Type: Interventional
• Enrollment (Actual): 320
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5K 1X3
      • Stratica Medical Inc.
  • British Columbia
    • Surrey, British Columbia, Canada, V3R 6A7
      • Guildford Dermatology Specialists
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 8X3
      • Durondel C.P. Inc./Dermatology Clinic
  • Ontario
    • Barrie, Ontario, Canada, L4M 6L2
      • Ultranova Skincare
    • Courtice, Ontario, Canada, L1E 3C3
      • Co-Medica Research Network Inc.
    • Hamilton, Ontario, Canada, L8N 1V6
      • Dermatrials Research Incorporated
    • London, Ontario, Canada, N6A 3H7
      • The Guenther Dermatology Research Centre
    • Markham, Ontario, Canada, L3P 1A8
      • Lynderm Research Inc.
    • Peterborough, Ontario, Canada, K9J 1Z2
      • Skin Centre for Dermatology
    • Waterloo, Ontario, Canada, N2J 1C4
      • K. Papp Clinical Research
    • Windsor, Ontario, Canada, N8W 1E6
      • XLR8 Medical Research
  • Quebec
    • Quebec City, Quebec, Canada, G1V 4X7
      • Centre De Recherche Dermatologique Du Quebec Metropolitain
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Omni Dermatology
  • California
    • Lomita, California, United States, 90717
      • Torrance Clinical Research Institute Inc.
    • San Diego, California, United States, 92121
      • Dermatology Cosmetic Laser Medical Associates of La Jolla, Inc.
  • Florida
    • Ormond Beach, Florida, United States, 32174
      • Leavitt Medical Associates of Florida
    • Tampa, Florida, United States, 33612
      • Clinical Research Center, Morsani Center for Advanced Healthcare
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Research Institute of Deaconess Clinic
    • Evansville, Indiana, United States, 47714
      • Hudson Dermatology, LLC
  • Maryland
    • Rockville, Maryland, United States, 20850
      • DermAssociates, PC
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Great Lakes Research Group, Inc.
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford Medical Center, Dept. of Dermatology
  • New Jersey
    • Verona, New Jersey, United States, 07044
      • The Dermatology Group, P.C.
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Following verbal and written information about the trial, subject must provide informed consent documented by signing the Informed Consent Form (ICF) prior to any trial-related procedures.
2. Part 1: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the face
3. Part 2: Subjects with 5 to 20 clinically typical, visible and discrete AKs on either the face or within a contiguous area of approximately 250 cm2 (40 in2) on the chest
4. Subject at least 18 years of age.

5. Female subjects must be of either:

   1. Non-childbearing potential, i.e., have a confirmed clinical history of sterility (e.g., the subject is without a uterus or have tubal ligation), or,
   2. Childbearing potential, provided there is a confirmed negative urine pregnancy test prior to trial treatment.
6. Female subjects of childbearing potential must use effective contraception throughout the study.

Exclusion Criteria:

1. Location of the treatment area within 5 cm (2 inches) of:

   1. an incompletely healed wound,
   2. a suspected basal or squamous cell carcinoma.
2. Prior treatment with ingenol mebutate gel on the treatment area.

3. Lesions in the treatment areas that have:

   1. atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horns) and/or
   2. recalcitrant disease (e.g., did not respond to cryotherapy on two previous occasions).
4. History or evidence of skin conditions other than the trial indication that would interfere with the evaluation of the trial medication (e.g., eczema, unstable psoriasis, xeroderma pigmentosum, Rosacea), at the investigator's discretion.
5. Use of cosmetic or therapeutic products and procedures which could interfere with the assessments of the treatment areas.
6. Any other disease or medical condition such as history or presence of cancer, cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunological, or neurological disease or disorder, that, in the opinion of the investigator, makes the subject unsuitable to participate in the trial.
7. Any abnormal laboratory or ECG findings that are clinically significant and would impact the safety of the subjects or the interpretation of the study results, as determined by the investigator.
8. Anticipated need for hospitalisation or out-patient surgery during the first 15 days after the first trial medication application. Note that cosmetic/therapeutic procedures are not excluded if they fall outside of the criteria detailed in Prohibited Therapies or Medications.
9. Known sensitivity or allergy to any of the ingredients in the LEO 43204.
10. Presence of acute sunburn within the treatment areas.
11. Current enrolment or participation in an investigational clinical trial within 30 days of entry into this trial.
12. Subjects previously randomised in the trial (Part 1 or 2).
13. Female subjects who are breastfeeding.
14. In the opinion of the investigator, the subject is unlikely to comply with the Clinical Study Protocol (e.g., alcoholism, drug dependency or psychotic state).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: LEO 43204 Formulation 1; Open-Label, Dose-Escalation, Once-Daily, 2-Day Treatment	Drug: LEO 43204 Formulation 1
Experimental: Part 1: LEO 43204 Formulation 2; Open-Label, Dose-Escalation, Once-Daily, 2-Day Treatment	Drug: LEO 43204 Formulation 2
Experimental: Part 2: LEO 43204 Formulation 1 Dose X; Double-Blind, Once-Daily, 2-Day Treatment	Drug: LEO 43204 Formulation 1 Dose X
Experimental: Part 2: LEO 43204 Formulation 1 Dose Y; Double-Blind, Once-Daily, 2-Day Treatment	Drug: LEO 43204 Formulation 1 Dose Y
Experimental: Part 2: LEO 43204 Formulation 2 Dose XX; Double-Blind, Once-Daily, 2-Day Treatment	Drug: LEO 43204 Formulation 2 Dose XX
Experimental: Part 2: LEO 43204 Formulation 2 Dose YY; Double-Blind, Once-Daily, 2-Day Treatment	Drug: LEO 43204 Formulation 2 Dose YY
Placebo Comparator: Part 2: Placebo Formulation 1; Double-Blind, Once-Daily, 2-Day Treatment	Drug: Placebo Formulation 1
Placebo Comparator: Part 2: Placebo Formulation 2; Double-Blind, Once-Daily, 2-Day Treatment	Drug: Placebo Formulation 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants Experiencing a Dose Limiting Toxicity (DLT) Based on Local Skin Responses (LSRs)	The number of participants experiencing DLTs are tabulated by treatment group. This was used to identify the maximum tolerated dose (MTD) of LEO 43204 after once daily treatment for 2 consecutive days.The MTD was defined as the highest dose level with less than 4 out of 12 participants(cohorts 1 to 4) or less than 6 out of 18 participants(cohorts 5 and 6) experiencing a DLT DLT was defined as one or more of the following 3 LSRs: Crusting Grade 4; Erosion/Ulceration Grade 4; Vesiculation/Pustulation Grade 4 or two or more of the following five LSRs: Erythema Grade 4; Crusting Grade 3; Swelling Grade 4; Erosion/Ulceration Grade 3; Vesiculation/Pustulation Grade 3 The Local Skin Responses consists of the following 6 categories: Erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration. Each individual LSR category are given a numeric grade of severity from 0-4. Grade 0 being no presence and 4 being the highest grade of severity.	From Day 1 up to and including Day 8
Part 2: Percent Reduction From Baseline in Actinic Keratosis (AK) Counts (Multiple Imputation)		At Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Percentage of Participants With Complete Clearance of Actinic Keratosis Lesions (AKs) (Multiple Imputation)	Complete clearance was defined as a 100% reduction from baseline in AK count. For treatment groups Vehicle, 0.006 and 0.012 the table shows the percentage of mean number of participants across imputations with complete clearance. For treatment group 0.018 the table shows the percentage of mean number of participants with complete clearance in observed cases.	At Week 8
Part 2: Percentage of Participants With Partial Clearance of AKs (Multiple Imputation)	Partial clearance was defined as at least 75% reduction from baseline in AK count. For treatment groups Vehicle, 0.006 and 0.012 the table shows the percentage of mean number of participants across imputations with partial clearance. For treatment group 0.018 the table shows the percentage of mean number of participants with partial clearance in observed cases.	At Week 8

Collaborators and Investigators

• Sponsor: LEO Pharma
• Investigators: Principal Investigator: Gary Goldenberg, MD, Mount Sinai School of Medicine, Dermatology Faculty

Publications and helpful links

General Publications

• Bourcier M, Stein Gold L, Guenther L, Andreassen CM, Selmer J, Goldenberg G. A dose-finding trial with a novel ingenol derivative (ingenol disoxate: LEO 43204) for field treatment of actinic keratosis on full face or 250 cm2 on the chest. J Dermatolog Treat. 2017 Nov;28(7):652-658. doi: 10.1080/09546634.2017.1303568. Epub 2017 Apr 4.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: August 12, 2013
• First Submitted That Met QC Criteria: August 12, 2013
• First Posted (Estimated): August 14, 2013

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Skin Diseases; Precancerous Conditions; Keratosis, Actinic; Keratosis
• Other Study ID Numbers: LP0084-1013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO