A Study to Evaluate the Efficacy and Safety of Tirbanibulin Ointment in Adult Participants With Actinic Keratosis (TirbAKare)

A Phase 3, Multicentre, Randomised, Double-blind, Vehicle-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Tirbanibulin 10 mg/g Ointment Applied to a Treatment Field Larger Than 25 cm^2 and up to 100 cm^2 in Adult Patients With Actinic Keratosis

The purpose of the study is to evaluate the efficacy and safety of tirbanibulin 10 milligrams per gram (mg/g) ointment when applied to a treatment field (TF) larger than 25 centimeter square (cm^2) and up to 100 cm^2 in adult participants with actinic keratosis (AK).

Study Overview

• Status: Completed
• Conditions: Keratosis, Actinic
• Intervention / Treatment: Drug: Tirbanibulin; Other: Vehicle ointment

• Study Type: Interventional
• Enrollment (Actual): 280
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Augsburg, Germany
    • Site 17
  • Bad Bentheim, Germany
    • Site 1
  • Bochum, Germany
    • Site 3
  • Dresden, Germany
    • Site 18
  • Hamburg, Germany
    • Site 2
  • Hamburg, Germany
    • Site 5
  • Mahlow, Germany
    • Site 4
  • Wuppertal, Germany
    • Site 6
• Italy
  • Bari, Italy
    • Site 24
  • Bologna, Italy
    • Site 25
  • Brescia, Italy
    • Site 19
  • Cagliari, Italy
    • Site 26
  • Florence, Italy
    • Site 23
  • Pisa, Italy
    • Site 22
  • Reggio Emilia, Italy
    • Site 27
  • Roma, Italy
    • Site 20
  • Roma, Italy
    • Site 21
  • Roma, Italy
    • Site 7
• Netherlands
  • Heemstede, Netherlands
    • Site 29
  • Maastricht, Netherlands
    • Site 28
• Poland
  • Krakow, Poland
    • Site 31
  • Ossy, Poland
    • Site 30
  • Warsaw, Poland
    • Site 10
  • Warsaw, Poland
    • Site 11
  • Warsaw, Poland
    • Site 9
  • Wroclaw, Poland
    • Site 8
• Spain
  • Barcelona, Spain
    • Site 12
  • Barcelona, Spain
    • Site 14
  • Barcelona, Spain
    • Site 34
  • Granada, Spain
    • Site 33
  • Madrid, Spain
    • Site 13
  • Salamanca, Spain
    • Site 32
  • Valencia, Spain
    • Site 15
  • Valencia, Spain
    • Site 35
  • Zaragoza, Spain
    • Site 16

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants having a TF on the face or balding scalp (excluding lips, eyelids, and inside nostrils and ears) that contains >= 4 to less than or equal to (<=) 12 clinically typical, visible, and discrete (non-confluent) AK lesions and measures more than 25 cm2 (example, one cheek) and up to approximately 100 cm2 (example, mid face).
• Participants willing to avoid excessive sunlight or UV light exposure, including the use of tanning beds, to the face or scalp during the study.
• Women of childbearing potential (WOCBP), that is, fertile, defined as a female in the life period from menarche and until becoming post-menopausal (no menses for 12 months without an alternative medical cause) or permanently sterile (with hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 3 months prior to screening) must have a negative urine pregnancy test using a highly sensitive method at screening and on Day 1 prior to treatment administration, be using highly effective methods of birth control for at least 30 days or 1 menstrual cycle, whichever is longer, and until at least 30 days or 1 menstrual period, whichever is longer, after the last dose of investigational product, agree to have pregnancy tests while in the study and at the end of the study, and agree not to be egg (oocyte) donors while on study and until at least 30 days or 1 menstrual period, whichever is longer, after the last dose of investigational product.
• Sexually active males with female partners who are WOCBP must agree to use two forms of contraception, one of which must be barrier contraception, from screening through 90 days after their last dose of study treatment. All non-sterile male participants must agree not to donate sperm or attempt conception from screening through 90 days following their last dose of study treatment.
• Participants should have ability to understand the purpose and risks of the trial, willingness and ability to comply with the protocol, and provided written informed consent in accordance with institutional and regulatory guidelines.

Exclusion Criteria:

• Participants with clinically atypical and/or rapidly changing AK lesions in the TF; hyperkeratotic or hypertrophic lesions, recalcitrant disease (defined as failure to respond to cryosurgery on 2 previous occasions) and/or cutaneous horn; history of invasive SCC, Bowen's disease, BCC, or other malignant tumors in the TF; any other dermatological disease that causes difficulty with examination.
• Location of the TF is on any location other than the face or balding scalp, within 5 centimeter (cm) of an incompletely healed wound, within 5 cm of a suspected BCC or other neoplasms, periorbital, lips, or nostrils.
• Participants having a previous treatment with tirbanibulin 10 mg/g ointment.
• Females who are pregnant or nursing or seeking to become pregnant.
• Participants having intention to use any concomitant medication that is not permitted by this protocol or failure to undergo the required washout period for a particular prohibited medication or therapy.
• Participants with anticipated need for inpatient hospitalization or inpatient surgery from Day 1 to Day 113.
• Participants with history of sensitivity and/or allergy to any of the ingredients in the study medication.
• Participants with significant abnormalities on the medical history, physical examination (PE) findings, vital signs, clinical chemistry, or hematology results that in the judgment of the investigator may interfere with the interpretation of the results.
• Participants with skin disease (example; atopic dermatitis, psoriasis, eczema) or condition (example; scarring, open wounds) that, in the opinion of the investigator, might interfere with the study conduct or evaluations, or which exposes the participant to unacceptable risk by study participation.
• Participants with significant uncontrolled or unstable medical diseases or conditions that, in the opinion of the investigator, would expose the participant to unacceptable risk by study participation.
• Participants who have participated in an investigational drug trial during which an investigational study medication was administered within 30 days or 5 half-lives of the investigational product, whichever is longer, before dosing in the current study.
• Participant who is employee or a relative to an employee at the research site or the Sponsor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirbanibulin 10 mg/g; Participants will apply tirbanibulin 10 mg/g ointment once daily for 5 consecutive days beginning on Day 1. All participants will be evaluated for efficacy, safety, and tolerability at Day 8, 15, 29, and 57. Participants who do not achieve complete clearance (CC) at Day 57 will receive a second 5-day course of the treatment. Participants receiving a second treatment course will also be evaluated for efficacy, safety, and tolerability at Day 64, 71, and 85.	Drug: Tirbanibulin; Participants will apply tirbanibulin ointment topically on the face or balding scalp with AK.; Other Names: Klisyri®
Placebo Comparator: Vehicle ointment; Participants will apply vehicle ointment once daily for 5 consecutive days beginning on Day 1. All participants will be evaluated for efficacy, safety, and tolerability at Day 8, 15, 29, and 57. Participants who do not achieve CC at Day 57 will receive a second 5-day course of the treatment. Participants receiving a second treatment course will also be evaluated for efficacy, safety, and tolerability at Day 64, 71, and 85.	Other: Vehicle ointment; Participants will apply vehicle ointment topically on the face or balding scalp with AK.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Lesion Count at Day 57	Percentage change from baseline in the AK lesion count will be assessed.	Baseline, Day 57

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With Partial Clearance (PC) at Day 57	PC is defined as proportion of participants achieving more than or equal to (>=) 75 percent (%) clearance of AK lesions in the TF on the face or scalp at Day 57.	At Day 57
Proportion of Participants With Complete Clearance (CC) at Day 57	CC is defined as proportion of participants achieving 100 percent clearance of AK lesions in the TF on the face or scalp at Day 57.	At Day 57
Proportion of Participants With Partial Clearance (PC) by Day 113		Baseline up to Day 113
Proportion of Participants With Complete Clearance (CC) by Day 113		Baseline up to Day 113
Local Tolerability Signs Composite Score at Specific Timepoints	Local tolerability signs composite score (0-18) at Specific Timepoints, defined as the sum of the scores graded from 0 (none) to 3 (severe) on all six individual tolerability sign categories (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) will be assessed. The higher score indicates severe symptoms.	At Day 1, 8, 15, 29, 57, 64, 71, 85, and 113
Maximum Local Tolerability Signs Composite Score in Treatment Course	Maximum local tolerability signs composite score (0-18) in treatment course, defined as the sum of the scores graded from 0 (none) to 3 (severe) on all six individual tolerability sign categories (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) will be assessed. The higher score indicates severe symptoms.	At Day 1, 8, 15, 29, 57, 64, 71, 85, and 113
Number of Participants With Adverse Event (AE), Serious Adverse Events (SAEs) and Adverse Events of Special Interests (AESIs)	An AE is defined as any untoward medical occurrence in a clinical trial participant, regardless of the administration of the IMP and its causal relationship to it unfavorable and unintended medical occurrence during the participant's participation in the trial, including deterioration of a pre-existing medical condition, an abnormal value in a laboratory assessment, or an abnormal finding in the physical examination. An SAE is any untoward medical occurrence that at any dose resulted in death; is life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in participant hospitalization; is congenital anomaly/birth defect or otherwise considered medically important. AESIs included skin cancers [including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma] appearing within or outside the TF during the study.	From Screening up to Day 113

Collaborators and Investigators

• Sponsor: Almirall, S.A.

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2023
• Primary Completion (Actual): April 30, 2025
• Study Completion (Actual): November 25, 2025

Study Registration Dates

• First Submitted: November 13, 2023
• First Submitted That Met QC Criteria: November 13, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Neoplasms; Actinic Keratosis; Actinic Keratoses; Keratosis, Actinic; Keratosis; Precancerous condition; Sun Damaged Skin
• Additional Relevant MeSH Terms: Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms; Keratosis, Actinic; Keratosis; Precancerous Conditions; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; tirbanibulin
• Other Study ID Numbers: M-14867-33; 2023-505487-11-00 (Ctis)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No