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

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

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.

Study Overview

• Status: Completed
• Conditions: Keratosis, Actinic
• Intervention / Treatment: Drug: Tirbanibulin ointment 1%

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Almirall Investigation Site 7
  • California
    • Encinitas, California, United States, 92024
      • Almirall Investigation Site 6
  • Florida
    • Sweetwater, Florida, United States, 33172
      • Almirall Investigation Site 3
  • Illinois
    • Rolling Meadows, Illinois, United States, 60008
      • Almirall Investigation Site 5
  • Texas
    • Austin, Texas, United States, 78759
      • Almirall Investigation Site 4
    • College Station, Texas, United States, 77845
      • Almirall Investigational Site 1
    • San Antonio, Texas, United States, 78213
      • Almirall Investigation Site 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

  1. Clinically atypical and/or rapidly changing AK lesions in the TF
  2. Hyperkeratotic or hypertrophic lesions, recalcitrant disease (had cryosurgery on 2 previous occasions) and/or cutaneous horn
  3. Confluent AK lesions (ie, non-discrete lesions defined as per inclusion criteria)
  4. History of invasive squamous cell carcinoma (SCC), Bowen's disease, basal cell carcinoma (BCC), or other malignant tumors in the TF
  5. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tirbanibulin (Klisyri®); 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 Actinic Keratosis (AK) lesions in the treatment field (TF) until completion of the response assessment period at Day 57.	Drug: Tirbanibulin ointment 1%; Applied topically for 5 days over a field of approximately 100 cm^2 on the face or balding scalp with AK.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Categorized by Local Tolerability Score by Visit for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration) at Day 5	Local tolerability score was 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 was applied. These symptoms were assessed by using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. Number of participants categorized by local tolerability score by visit for each individual signs (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) at Day 5 were reported.	Baseline, Day 5
Number of Participants Categorized by Local Tolerability Score by Visit for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration) at Day 8	Local tolerability score was 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 was applied. These symptoms were assessed by using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. Number of participants categorized by local tolerability score by visit for each individual signs (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) at Day 8 were reported.	Baseline, Day 8
Number of Participants Categorized by Local Tolerability Score by Visit for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration) at Day 15	Local tolerability score was 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 was applied. These symptoms were assessed by using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. Number of participants categorized by local tolerability score by visit for each individual signs (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) at Day 15 were reported.	Baseline, Day 15
Number of Participants Categorized by Local Tolerability Score by Visit for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration) at Day 29	Local tolerability score was 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 was applied. These symptoms were assessed by using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. Number of participants categorized by local tolerability score by visit for each individual signs (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) at Day 29 were reported.	Baseline, Day 29
Number of Participants Categorized by Local Tolerability Score by Visit for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration) at Day 57	Local tolerability score was 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 was applied. These symptoms were assessed by using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. Number of participants categorized by local tolerability score by visit for each individual signs (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) at Day 57 were reported.	Baseline, Day 57
Number of Participants With Maximum Local Tolerability Score Post-baseline for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration)	Maximum local tolerability score post baseline was defined as the highest grade of any LSR reported at any post-baseline visits for a participant. Local tolerability score was assessed for signs erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. If a participant maximum individual sign local tolerability score stayed at 0 throughout the study, the participant was considered censored at last local tolerability score observation. Number of participants with maximum local tolerability score for each individual signs including erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration were reported.	Baseline, Maximum post-baseline (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 (in days) for each individual sign was calculated as [Date of first post-baseline occurrence of maximum local tolerability score for this individual sign - Date of first dose]. If a participant maximum individual sign LTA score stays at 0 throughout the study, the participants was considered censored at their last LTA score observation. Maximum local tolerability score was assessed for each signs using a 4 - point scale of 0 - 3, where 0 = absent, 1= mild, 2= moderate and 3 = severe. The higher score indicates severe symptoms. Time to maximum local tolerability score for erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration was reported.	Baseline up to Day 57
Local Tolerability Signs Total Composite Score by Visit at Day 5	Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score assessed from baseline up to Day 5 was reported.	Baseline, Day 5
Local Tolerability Signs Total Composite Score by Visit at Day 8	Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score by visit at Day 8 was reported.	Baseline, Day 8
Local Tolerability Signs Total Composite Score by Visit at Day 15	Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score by visit at Day 15 was reported.	Baseline, Day 15
Local Tolerability Signs Total Composite Score by Visit at Day 29	Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score by visit at Day 29 was reported.	Baseline, Day 29
Local Tolerability Signs Total Composite Score by Visit at Day 57	Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score by visit at Day 57 was reported.	Baseline, Day 57
Maximum Local Tolerability Signs Total Composite Score Post Baseline	The maximum local tolerability signs composite score across visits was derived as the maximum local tolerability composite score observed post-baseline. Local tolerability signs composite score was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Maximum local tolerability signs total composite score post baseline was reported.	Baseline, Maximum post-baseline (up to Day 57)
Time to Maximum Local Tolerability Total Composite Score	Time to maximum composite local tolerability score (in days) was calculated as (Date of first post-baseline occurrence of maximum composite local tolerability score - Date of first dose). The maximum local tolerability signs composite score across visits was derived as the maximum local tolerability composite score observed post-baseline. Local tolerability signs composite score was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. If a participant's maximum composite local tolerability score stays at 0 throughout the study, the participant was considered censored at their last local tolerability score observation. Time to maximum local tolerability total composite score was reported.	Baseline up to Day 57
Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 5	Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 5 was reported.	Baseline, Day 5
Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 8	Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 8 was reported.	Baseline, Day 8
Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 15	Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 15 was reported.	Baseline, Day 15
Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 29	Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 29 was reported.	Baseline, Day 29
Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 57	Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 57 was reported.	Baseline, Day 57
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)	TEAEs were defined as either those adverse events (AEs) with an onset after dosing or those pre-existing conditions that worsened after dosing. An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an Investigational Product. An SAE with any untoward medical occurrence that at any dose, resulted in death, was life-threatening, 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, or any other medically important event that may jeopardize the patient or require intervention to prevent one of the other outcomes. AESI's included in this study were skin cancers (including basal cell carcinoma, squamous cell carcinoma, and melanoma) based on their relevance for the current intended use. TEAEs included both serious and non-serious AEs.	Baseline up to Day 57
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters	Laboratory parameters included blood chemistry, hamatology, and urinalysis. Clinically significant laboratory abnormalities assessment was based on Investigator interpretation. Number of participants with clinically significant abnormalities in laboratory parameters (included hematology, blood chemistry and urinalysis) were reported.	Baseline up to Day 57
Number of Participants With Clinically Significant Abnormalities in Vital Signs	Vital signs included measurement of pulse rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Clinically significant vital signs abnormalities assessment was based on Investigator interpretation. Number of participants with clinically significant abnormalities in vital signs were reported.	Baseline up to Day 57
Number of Participants With Clinically Significant Abnormalities in Physical Examination	Physical examination included weight and height measurements. Clinically significant physical examination abnormalities assessment was based on Investigator interpretation. Number of participants with clinically significant abnormalities in physical examination were reported.	Baseline up to Day 57
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)	ECG included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals parameters measurement. Clinically significant ECGs abnormalities assessment was based on Investigator interpretation. Number of participants with clinically significant abnormalities in ECG were reported.	Baseline up to Day 57

Collaborators and Investigators

• Sponsor: Almirall, S.A.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2022
• Primary Completion (Actual): December 28, 2022
• Study Completion (Actual): December 28, 2022

Study Registration Dates

• First Submitted: March 1, 2022
• First Submitted That Met QC Criteria: March 10, 2022
• First Posted (Actual): March 15, 2022

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: December 28, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Tirbanibulin
• Other Study ID Numbers: M-14867-32

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