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

NCT01922050 | Completed Phase 1 Results

• 1 other identifier: LP0084-1013
• Study Type: interventional
• Target: 320
• Locations: 2 countries
• Sites: 25

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

Conditions

Actinic Keratosis

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Part 2: Percentage of Participants With Complete Clearance of Actinic Keratosis Lesions (AKs) (Multiple Imputation)

  At Week 8

• Part 2: Percentage of Participants With Partial Clearance of AKs (Multiple Imputation)

  At Week 8

Study Arms (8)

Part 1: LEO 43204 Formulation 1

EXPERIMENTAL

Open-Label, Dose-Escalation, Once-Daily, 2-Day Treatment

Drug: LEO 43204 Formulation 1

Part 1: LEO 43204 Formulation 2

EXPERIMENTAL

Open-Label, Dose-Escalation, Once-Daily, 2-Day Treatment

Drug: LEO 43204 Formulation 2

Part 2: LEO 43204 Formulation 1 Dose X

EXPERIMENTAL

Double-Blind, Once-Daily, 2-Day Treatment

Drug: LEO 43204 Formulation 1 Dose X

Part 2: LEO 43204 Formulation 1 Dose Y

EXPERIMENTAL

Double-Blind, Once-Daily, 2-Day Treatment

Drug: LEO 43204 Formulation 1 Dose Y

Part 2: LEO 43204 Formulation 2 Dose XX

EXPERIMENTAL

Double-Blind, Once-Daily, 2-Day Treatment

Drug: LEO 43204 Formulation 2 Dose XX

Part 2: LEO 43204 Formulation 2 Dose YY

EXPERIMENTAL

Double-Blind, Once-Daily, 2-Day Treatment

Drug: LEO 43204 Formulation 2 Dose YY

Part 2: Placebo Formulation 1

PLACEBO COMPARATOR

Double-Blind, Once-Daily, 2-Day Treatment

Drug: Placebo Formulation 1

Part 2: Placebo Formulation 2

PLACEBO COMPARATOR

Double-Blind, Once-Daily, 2-Day Treatment

Drug: Placebo Formulation 2

Interventions

LEO 43204 Formulation 1 DRUG

Part 1: LEO 43204 Formulation 1

LEO 43204 Formulation 2 DRUG

Part 1: LEO 43204 Formulation 2

LEO 43204 Formulation 1 Dose X DRUG

Part 2: LEO 43204 Formulation 1 Dose X

LEO 43204 Formulation 1 Dose Y DRUG

Part 2: LEO 43204 Formulation 1 Dose Y

LEO 43204 Formulation 2 Dose XX DRUG

Part 2: LEO 43204 Formulation 2 Dose XX

LEO 43204 Formulation 2 Dose YY DRUG

Part 2: LEO 43204 Formulation 2 Dose YY

Placebo Formulation 1 DRUG

Part 2: Placebo Formulation 1

Placebo Formulation 2 DRUG

Part 2: Placebo Formulation 2

Eligibility Criteria

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

You may qualify if:

• 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.
• Part 1: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the face
• 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
• Subject at least 18 years of age.
• Female subjects must be of either:
• 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,
• Childbearing potential, provided there is a confirmed negative urine pregnancy test prior to trial treatment.
• Female subjects of childbearing potential must use effective contraception throughout the study.

You may not qualify if:

• Location of the treatment area within 5 cm (2 inches) of:
• an incompletely healed wound,
• a suspected basal or squamous cell carcinoma.
• 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).
• 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.
• Use of cosmetic or therapeutic products and procedures which could interfere with the assessments of the treatment areas.
• 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.
• 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.
• 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.
• Known sensitivity or allergy to any of the ingredients in the LEO 43204.
• Presence of acute sunburn within the treatment areas.
• Current enrolment or participation in an investigational clinical trial within 30 days of entry into this trial.

Sponsors & Collaborators

• LEO Pharma: lead

Study Sites (25)

Omni Dermatology

Phoenix, Arizona, 85018, United States

Location

Torrance Clinical Research Institute Inc.

Lomita, California, 90717, United States

Location

Dermatology Cosmetic Laser Medical Associates of La Jolla, Inc.

San Diego, California, 92121, United States

Location

Leavitt Medical Associates of Florida

Ormond Beach, Florida, 32174, United States

Location

Clinical Research Center, Morsani Center for Advanced Healthcare

Tampa, Florida, 33612, United States

Location

Research Institute of Deaconess Clinic

Evansville, Indiana, 47713, United States

Location

Hudson Dermatology, LLC

Evansville, Indiana, 47714, United States

Location

DermAssociates, PC

Rockville, Maryland, 20850, United States

Location

Great Lakes Research Group, Inc.

Bay City, Michigan, 48706, United States

Location

Henry Ford Medical Center, Dept. of Dermatology

West Bloomfield, Michigan, 48322, United States

Location

The Dermatology Group, P.C.

Verona, New Jersey, 07044, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

Stratica Medical Inc.

Edmonton, Alberta, T5K 1X3, Canada

Location

Guildford Dermatology Specialists

Surrey, British Columbia, V3R 6A7, Canada

Location

Durondel C.P. Inc./Dermatology Clinic

Moncton, New Brunswick, E1C 8X3, Canada

Location

Ultranova Skincare

Barrie, Ontario, L4M 6L2, Canada

Location

Co-Medica Research Network Inc.

Courtice, Ontario, L1E 3C3, Canada

Location

Dermatrials Research Incorporated

Hamilton, Ontario, L8N 1V6, Canada

Location

The Guenther Dermatology Research Centre

London, Ontario, N6A 3H7, Canada

Location

Lynderm Research Inc.

Markham, Ontario, L3P 1A8, Canada

Location

SKiN Centre for Dermatology

Peterborough, Ontario, K9J 1Z2, Canada

Location

K. Papp Clinical Research

Waterloo, Ontario, N2J 1C4, Canada

Location

XLR8 Medical Research

Windsor, Ontario, N8W 1E6, Canada

Location

Centre de Recherche Dermatologique du Quebec Metropolitain

Québec, Quebec, G1V 4X7, Canada

Location

Related Publications (1)

• 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.

  PMID: 28264612 DERIVED

MeSH Terms

Conditions

Keratosis, Actinic

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Clinical Trial Disclosure Specialist
• Organization: LEO Pharma A/S

disclosure@leo-pharma.com

Study Officials

• Gary Goldenberg, MD

  Mount Sinai School of Medicine, Dermatology Faculty

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2013
• First Posted: August 14, 2013
• Study Start: October 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: March 6, 2025
• Results First Posted: February 27, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (12); US (13)