Safety and Efficacy of Escalating Doses of LEO 43204 Applied Once Daily for Two Consecutive Days on Approximately 250 cm2 on Trunk and Extremities in Subjects With Actinic Keratosis

Phase 1

Completed

• Conditions: Actinic Keratosis
• Interventions: Drug: LEO 43204; Drug: Placebo

• Registration Number: NCT02120456
• Lead Sponsor: LEO Pharma

Brief Summary

Part 1: To identify Maximum Tolerated Dose (MTD) levels of LEO 43204 after once daily treatment for two consecutive days

Part 2: To evaluate the efficacy of LEO 43204 in two doses after once daily treatment for two consecutive days compared to vehicle

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-04-18
• Study First Submitted QC: 2014-04-21
• Study First Posted: 2014-04-22
• Study Start: 2014-05
• Primary Completion: 2015-05
• Study Completion: 2015-05
• Disposition First Submitted: 2016-04-18
• Disposition First Submitted QC: 2016-04-18
• Disposition First Posted: 2016-05-17
• Status Verified: 2018-11
• Results First Submitted: 2018-11-14
• Results First Submitted QC: 2018-12-28
• Results First Posted: 2019-01-04
• Last Update Submitted: 2025-02-21
• Last Update Posted: 2025-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 224

Inclusion Criteria

• Part 1: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the arm
• Part 2: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the extremities or trunk

Exclusion Criteria

• Location of the treatment area

  • within 5 cm of an incompletely healed wound
  • within 5 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)

• Prior treatment with ingenol mebutate gel on the treatment area

• Lesions in the treatment areas that have:

  • atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horns) and/or
  • recalcitrant disease (e.g., did not respond to cryotherapy on two previous occasions)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LEO 43204	LEO 43204	Open-label, dose-escalation, 2-day treatment
Placebo	Placebo	Placebo once daily for two days
LEO 43204 Dose 0.1%	LEO 43204	LEO 43204 dose 0.1% once daily for two consecutive days
LEO 43204 Dose 0.075%	LEO 43204	LEO 43204 dose 0.075% once daily for two days

Primary Outcome Measures

Name	Time	Method
Part 1: Participants Experiencing Dose Limiting Toxicity (DLT) Based on Local Skin Responses (LSRs)	From Day 1 up to and including Day 8	The number participants experiencing a DLT was used to identify the maximum tolerated dose(MTD) levels of LEO 43204 after once daily treatment for 2 consecutive days.The MTD was defined as the highest dose level at which less than 4 out of 12 participants experienced a DLT.; A DLT was defined as one or more of the following three LSRs: * Crusting Grade 4; * Erosion/Ulceration Grade 4; * Vesiculation/Pustulation Grade 4; or two or more of the following five LSRs: * Crusting Grade 3; * Swelling Grade 4; * Erosion/Ulceration Grade 3; * Vesiculation/Pustulation Grade 3; or other clinically relevant signs or symptoms observed, which the Investigator judged to be counted as a DLT.; The LSRs consists of the following 6 categories: Erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration. Each individual LSR category was given a numeric grade of severity from 0-4. Grade 0 being no presence and Grade 4 being the highest grade of severity.
Part 2: Percent Reduction From Baseline in Actinic Keratosis (AK) Count	From baseline to Week 8	Percent reduction from baseline in clinically visible actinic keratosis lesions (AKs) identified in the treatment area.

Secondary Outcome Measures

Name	Time	Method
Part 2: Participants With Complete Clearance of AKs (Last Observation Carried Forward [LOCF])	From baseline to Week 8	Complete clearance was defined as a 100% reduction from baseline in AK count.
Part 2: Participants With Partial Clearance of AKs (LOCF)	From baseline to Week 8	Partial clearance was defined as at least 75% reduction from baseline in AK count.

Trial Locations

Locations (21)

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

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

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Pflugerville Dermatology Clinical Research Center, Inc.; 🇺🇸 Pflugerville, Texas, United States

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

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

Deaconess Clinic, Inc.; 🇺🇸 Evansville, Indiana, United States

Dermatrials Research Incorporated; 🇨🇦 Hamilton, Ontario, Canada

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

Indiana Clinical Trials Center; 🇺🇸 Plainfield, Indiana, United States

Skin Care Centre; 🇨🇦 Vancouver, British Columbia, Canada

Enverus Medical; 🇨🇦 Surrey, British Columbia, Canada

UltraNova Skincare; 🇨🇦 Barrie, Ontario, Canada

Omni Dermatology; 🇺🇸 Phoenix, Arizona, United States

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

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

Dermatology Associates and Research; 🇺🇸 Coral Gables, Florida, United States

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

Kirk Barber Research; 🇨🇦 Calgary, Alberta, Canada

Winnipeg Clinic Dermatology Research; 🇨🇦 Winnipeg, Manitoba, Canada

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