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

Phase 1

Completed

• Conditions: Actinic Keratosis
• Interventions: Drug: LEO 43204 Formulation 2; Drug: Placebo Formulation 2; Drug: LEO 43204 Formulation 1; 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

• Registration Number: NCT01922050
• Lead Sponsor: LEO Pharma

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-08-12
• Study First Submitted QC: 2013-08-12
• Study First Posted: 2013-08-14
• Study Start: 2013-10
• Primary Completion: 2014-11
• Study Completion: 2014-11
• Disposition First Submitted: 2015-10-20
• Disposition First Submitted QC: 2015-10-20
• Disposition First Posted: 2015-11-11
• Results First Submitted: 2018-11-14
• Status Verified: 2019-02
• Results First Submitted QC: 2019-02-06
• Results First Posted: 2019-02-27
• Last Update Submitted: 2025-02-21
• Last Update Posted: 2025-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 320

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1: LEO 43204 Formulation 2	LEO 43204 Formulation 2	Open-Label, Dose-Escalation, Once-Daily, 2-Day Treatment
Part 2: Placebo Formulation 2	Placebo Formulation 2	Double-Blind, Once-Daily, 2-Day Treatment
Part 1: LEO 43204 Formulation 1	LEO 43204 Formulation 1	Open-Label, Dose-Escalation, Once-Daily, 2-Day Treatment
Part 2: LEO 43204 Formulation 1 Dose X	LEO 43204 Formulation 1 Dose X	Double-Blind, Once-Daily, 2-Day Treatment
Part 2: LEO 43204 Formulation 1 Dose Y	LEO 43204 Formulation 1 Dose Y	Double-Blind, Once-Daily, 2-Day Treatment
Part 2: LEO 43204 Formulation 2 Dose XX	LEO 43204 Formulation 2 Dose XX	Double-Blind, Once-Daily, 2-Day Treatment
Part 2: LEO 43204 Formulation 2 Dose YY	LEO 43204 Formulation 2 Dose YY	Double-Blind, Once-Daily, 2-Day Treatment
Part 2: Placebo Formulation 1	Placebo Formulation 1	Double-Blind, Once-Daily, 2-Day Treatment

Primary Outcome Measures

Name	Time	Method
Part 1: Number of Participants Experiencing a Dose Limiting Toxicity (DLT) Based on Local Skin Responses (LSRs)	From Day 1 up to and including Day 8	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.
Part 2: Percent Reduction From Baseline in Actinic Keratosis (AK) Counts (Multiple Imputation)	At Week 8

Secondary Outcome Measures

Name	Time	Method
Part 2: Percentage of Participants With Partial Clearance of AKs (Multiple Imputation)	At Week 8	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.
Part 2: Percentage of Participants With Complete Clearance of Actinic Keratosis Lesions (AKs) (Multiple Imputation)	At Week 8	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.

Trial Locations

Locations (25)

Torrance Clinical Research Institute Inc.; 🇺🇸 Lomita, California, United States

Dermatology Cosmetic Laser Medical Associates of La Jolla, Inc.; 🇺🇸 San Diego, California, United States

Omni Dermatology; 🇺🇸 Phoenix, Arizona, United States

Research Institute of Deaconess Clinic; 🇺🇸 Evansville, Indiana, United States

The Dermatology Group, P.C.; 🇺🇸 Verona, New Jersey, United States

The Guenther Dermatology Research Centre; 🇨🇦 London, Ontario, Canada

Mount Sinai School of Medicine; 🇺🇸 New York, New York, United States

Clinical Research Center, Morsani Center for Advanced Healthcare; 🇺🇸 Tampa, Florida, United States

Hudson Dermatology, LLC; 🇺🇸 Evansville, Indiana, United States

DermAssociates, PC; 🇺🇸 Rockville, Maryland, United States

Great Lakes Research Group, Inc.; 🇺🇸 Bay City, Michigan, United States

Henry Ford Medical Center, Dept. of Dermatology; 🇺🇸 West Bloomfield, Michigan, United States

Stratica Medical Inc.; 🇨🇦 Edmonton, Alberta, Canada

Guildford Dermatology Specialists; 🇨🇦 Surrey, British Columbia, Canada

Durondel C.P. Inc./Dermatology Clinic; 🇨🇦 Moncton, New Brunswick, Canada

Co-Medica Research Network Inc.; 🇨🇦 Courtice, Ontario, Canada

Ultranova Skincare; 🇨🇦 Barrie, Ontario, Canada

Dermatrials Research Incorporated; 🇨🇦 Hamilton, Ontario, Canada

Lynderm Research Inc.; 🇨🇦 Markham, Ontario, Canada

SKiN Centre for Dermatology; 🇨🇦 Peterborough, Ontario, Canada

K. Papp Clinical Research; 🇨🇦 Waterloo, Ontario, Canada

XLR8 Medical Research; 🇨🇦 Windsor, Ontario, Canada

Centre de Recherche Dermatologique du Quebec Metropolitain; 🇨🇦 Quebec City, Quebec, Canada

Leavitt Medical Associates of Florida; 🇺🇸 Ormond Beach, Florida, United States

Clinical Trials of Texas, Inc.; 🇺🇸 San Antonio, Texas, United States