A Study to Evaluate the Safety and Tolerability of Tirbanibulin Ointment 1% in Adult Participants With Actinic Keratosis

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety, tolerability and treatment effect of tirbanibulin ointment 1% when applied to a field of approximately 100 cm^2 on the face or balding scalp.

Official Title
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A Phase 3, Multicenter, Open-label, Single-arm Study to Evaluate the Safety and Tolerability of Tirbanibulin Ointment 1% Applied to a Field of Approximately 100 cm2 on the Face or Balding Scalp in Adult Patients With Actinic Keratosis

Conditions
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Keratosis, Actinic

Intervention / Treatment
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* Drug: Tirbanibulin ointment 1%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having a treatment field (TF) on the face or balding scalp (excluding lips, eyelids, and inside nostrils and ears) that measures approximately 100 cm^2 (eg, mid face) and contains 4 to 12 clinically typical, visible, and discrete actinic keratosis (AK) lesions within the TF Willing to avoid excessive sunlight or ultraviolet (UV) light exposure, including the use of tanning beds, to the face or scalp during the study 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: Presence in the TF of Clinically atypical and/or rapidly changing AK lesions in the TF Hyperkeratotic or hypertrophic lesions, recalcitrant disease (had cryosurgery on 2 previous occasions) and/or cutaneous horn Confluent AK lesions (ie, non-discrete lesions defined as per inclusion criteria) History of invasive squamous cell carcinoma (SCC), Bowen's disease, basal cell carcinoma (BCC), or other malignant tumors in the TF Any other dermatological disease that causes difficulty with examination Previous treatment with tirbanibulin ointment 1%. Anticipated need for inpatient hospitalization or inpatient surgery from Day 1 to Day 57 Treatment with 5-fluorouracil, imiquimod, ingenol mebutate, diclofenac, photodynamic therapy, or other treatments for AK within the TF or within 2 cm of the TF, within 8 weeks prior to the Screening visit Use of systemic retinoids (eg, isotretinoin, acitretin, bexarotene) within 6 months prior to the Screening visit

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tirbanibulin (Klisyri®)<br>Participants will apply tirbanibulin ointment 1% once daily for 5 days beginning Day 1. Participants will be evaluated for safety, tolerability, and the presence of AK lesions in the treatment field (TF) until completion of the response assessment period at Day 57 | Drug: Tirbanibulin ointment 1%<br>* Participants will apply Tirbanibulin ointment 1% topically for 5 days over a field of approximately 100 cm^2 on the face or balding scalp with Actinic Keratosis (AK).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Tolerability Score for Signs Including Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration | Local tolerability score is evaluated by investigator in terms of presence and absence of erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration signs and its severity in the areas of body where medication is applied. These symptoms are assessed by using a 4 - point scale of 0 - 3, where 0 = none and 3 = severe. The higher score indicates severe symptoms. | Up to Day 57 | 
| Change from Baseline in Maximum Local Tolerability Score | Change from baseline in maximum local tolerability score will be assessed for erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. Local tolerability score for each signs are assessed by using a 4 - point scale of 0 - 3, where 0 = none and 3 = severe. | Baseline to up to Day 57 | 
| Time to Maximum Local Tolerability Score for Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration | Time to maximum local tolerability score for erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration will be assessed. The higher score indicates severe symptoms. | Baseline up to Day 57 | 
| Local Tolerability Signs Composite Score | Local tolerability signs composite score (0-18) by visit, defined as the sum of the scores graded from 0 to 3 on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. | Baseline up to Day 57 | 
| Change From Baseline in Maximum Local Tolerability Signs Composite Score | Change from baseline in maximum local tolerability signs composite score will be assessed for erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. | Baseline up to Day 57 | 
| Time to Maximum Local Tolerability Composite Score | Time to maximum local tolerability composite score for erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration will be assessed. | Baseline up to Day 57 | 
| Number of Participants with change from baseline in hypopigmentation in treatment field | Number of participants with change from baseline in hypopigmentation in the treatment area will be assessed. | Baseline up to Day 57 | 
| Number of Participants with change from baseline in hyperpigmentation in treatment field | Number of participants with change from baseline in hyperpigmentation in the treatment area will be assessed. | Baseline up to Day 57 | 
| Number of Participants with change from baseline in Scarring in treatment field | Number of participants with change from baseline in scarring in the treatment area will be assessed. | Baseline up to Day 57 | 
| Number of Participants With Any Treatment-emergent Adverse Events | An Adverse Event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered an Investigational Product. An AE did not necessarily have a causal relationship with the medicinal product. Treatment-emergent Adverse Events (TEAEs) were defined as either those AEs with an onset after dosing or those pre-existing conditions that worsened after dosing. TEAEs included both serious and non-serious TEAEs. | Baseline up to Day 57 | 
| Number of Participants With Any Treatment-emergent Serious Adverse Events | A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that at any dose, resulted in death, was life-threatening (i.e, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). | Baseline to up to Day 57 | 
| Number of Participants With Clinically Significant Laboratory Abnormalities | Number of participants with clinically significant laboratory parameters (included hematology, blood chemistry and urinalysis) will be assessed. | Up to Day 57 | 
| Number of Participants With Vital Signs Abnormalities | Number of participants with vital signs (included measurement of pulse rate, systolic and diastolic blood pressure, respiratory rate, and body temperature) will be reported | Up to Day 57 | 
| Number of Participants With Physical Examination Abnormalities | Number of participants with physical examination abnormalities (weight and height) measurements will be reported. | Up to Day 57 | 
| Number of Participants With Electrocardiograms (ECGs) Abnormalities | Number of participants with ECG (heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals) abnormalities will be reported. | Up to Day 57 |