Clinical trial NCT01922050: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Actinic Keratosis
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2013-08-14
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: 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).

Primary outcomes:
measure: Part 1: Number of Participants Experiencing a Dose Limiting Toxicity (DLT) Based on Local Skin Responses (LSRs)
timeFrame: From Day 1 up to and including Day 8
measure: Part 2: Percent Reduction From Baseline in Actinic Keratosis (AK) Counts (Multiple Imputation)
timeFrame: At Week 8
Secondary outcomes:
measure: Part 2: Percentage of Participants With Complete Clearance of Actinic Keratosis Lesions (AKs) (Multiple Imputation)
timeFrame: At Week 8
measure: Part 2: Percentage of Participants With Partial Clearance of AKs (Multiple Imputation)
timeFrame: At Week 8
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Omni Dermatology
state: Arizona
city: Lomita
country: United States
facility: Torrance Clinical Research Institute Inc.
state: California
city: San Diego
country: United States
facility: Dermatology Cosmetic Laser Medical Associates of La Jolla, Inc.
state: California
city: Ormond Beach
country: United States
facility: Leavitt Medical Associates of Florida
state: Florida
city: Tampa
country: United States
facility: Clinical Research Center, Morsani Center for Advanced Healthcare
state: Florida
city: Evansville
country: United States
facility: Research Institute of Deaconess Clinic
state: Indiana
city: Evansville
country: United States
facility: Hudson Dermatology, LLC
state: Indiana
city: Rockville
country: United States
facility: DermAssociates, PC
state: Maryland
city: Bay City
country: United States
facility: Great Lakes Research Group, Inc.
state: Michigan
city: West Bloomfield
country: United States
facility: Henry Ford Medical Center, Dept. of Dermatology
state: Michigan
city: Verona
country: United States
facility: The Dermatology Group, P.C.
state: New Jersey
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Edmonton
country: Canada
facility: Stratica Medical Inc.
state: Alberta
city: Surrey
country: Canada
facility: Guildford Dermatology Specialists
state: British Columbia
city: Moncton
country: Canada
facility: Durondel C.P. Inc./Dermatology Clinic
state: New Brunswick
city: Barrie
country: Canada
facility: Ultranova Skincare
state: Ontario
city: Courtice
country: Canada
facility: Co-Medica Research Network Inc.
state: Ontario
city: Hamilton
country: Canada
facility: Dermatrials Research Incorporated
state: Ontario
city: London
country: Canada
facility: The Guenther Dermatology Research Centre
state: Ontario
city: Markham
country: Canada
facility: Lynderm Research Inc.
state: Ontario
city: Peterborough
country: Canada
facility: SKiN Centre for Dermatology
state: Ontario
city: Waterloo
country: Canada
facility: K. Papp Clinical Research
state: Ontario
city: Windsor
country: Canada
facility: XLR8 Medical Research
state: Ontario
city: Quebec City
country: Canada
facility: Centre de Recherche Dermatologique du Quebec Metropolitain
state: Quebec
Study officials:
affiliation: Mount Sinai School of Medicine, Dermatology Faculty
name: Gary Goldenberg, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.