A Study of Tirbanibulin on the Wellbeing of Participants With Actinic Keratoses

Actinic Keratosis Clinical Trial

Official title:

Open Phase IV Study to Assess the Impact of Tirbanibulin on the Wellbeing of Patients With Actinic Keratoses (TIRBASKIN)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05741294
• Other study ID #: M-14789-42
• Secondary ID: 2022-001251-16
• Status: Completed
• Phase: Phase 4
• Start date: January 17, 2023
• Est. completion date: December 21, 2023

Study information

• Verified date: January 2024
• Source: Almirall, S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to assess treatment satisfaction on Day 57 in participants with Actinic Keratoses (AK) of the face or scalp following treatment with tirbanibulin ointment 1 percent (%) administered once daily for 5 consecutive days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 342
• Est. completion date: December 21, 2023
• Est. primary completion date: December 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Written informed consent.

2. Males or females aged greater than or equal to (>=)18 years.

3. Diagnosis of clinically typical AK in one contiguous area on the face or scalp with a treatment area of 25^cm2 containing 4-8 AK lesions.

4. Participants not previously treated for AK on the current treatment area of the face or scalp in the last 6 months. However, previous AK treatment in other small areas (up to 25^cm2) in the last greater than >1 to less than <6 months is allowed.

5. Females must be postmenopausal (A female said to be postmenopausal should be >45 years of age with at least 12 months of amenorrhea), surgically sterile (by hysterectomy, bilateral oophorectomy, or tubal ligation); or, if of child-bearing potential, must be using highly effective contraception for at least 30 days or 1 menstrual cycle, whichever is longer, prior to study treatment and must agree to continue to use highly effective contraception for at least 30 days following their last dose of study treatment. Highly effective contraception includes oral hormonal contraceptives, hormonal contraceptive intercourse.

6. Sexually active males who have not had a vasectomy, and whose partner is reproductively capable, must agree to use barrier contraception from Screening through 90 days after their last dose of study treatment.

7. All participants must agree not to donate sperm or eggs from screening through 90 days following their last dose of study treatment.

8. Females of child-bearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 0 prior to dose administration.

9. Willing to avoid excessive sun or UV (ultraviolet light) light exposure to the face or scalp.

Exclusion Criteria:

1. Clinically atypical and/or rapidly changing AK lesions.

2. Location of the treatment area is within 5 cm of an incompletely healed wound or a suspected basal cell carcinoma (BCC)/squamous cell carcinoma (SCC).

3. Skin disease (e.g., atopic dermatitis, psoriasis, eczema) or condition (e.g., open wounds, scarring) in the treatment area that might interfere with the study results or suppose an unacceptable risk.

4. History of sensitivity to any of the ingredients in the tirbanibulin formulation.

5. Participated in a clinical 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.

6. Participants with a history of tirbanibulin treatment for AK lesions and participants who are currently on tirbanibulin treatment for AK lesions.

7. Use of immunomodulators (e.g., azathioprine), cytotoxic drugs (e.g., cyclophosphamide, vinblastine, chlorambucil, methotrexate) or interferons/ interferon inducers and systemic immunosuppressive agents (e.g., cyclosporine, prednisone, methotrexate, alefacept, infliximab) within 4 weeks prior to the Screening visit, except for organ transplant recipients under stable immunosuppressive therapy for 6 months.

8. Use of systemic retinoids (e.g., isotretinoin, acitretin, bexarotene) within 6 months prior to the Screening visit.

9. Use of the following therapies and/or medications within 2 weeks prior to the Screening Visit:

• Cosmetic or therapeutic procedures (e.g., use of liquid nitrogen, surgical excision, curettage, dermabrasion, medium or greater depth chemical peel, laser resurfacing) within the treatment area or within 2 cm of the selected treatment area

• Acid-containing therapeutic products (e.g., salicylic acid or fruit acids, such as alpha- and beta-hydroxyl acids and glycolic acids), topical retinoids, or light chemical peels within the treatment area or within 2 cm of the selected treatment area

• Topical salves (nonmedicated/nonirritant lotion and cream are acceptable) or topical steroids within the treatment area or within 2 cm of the selected treatment area; artificial tanners within the treatment area or within 5 cm of the selected treatment area.

10. Females who are pregnant or nursing.

Related Conditions & MeSH terms

• Actinic Keratosis
• Keratosis
• Keratosis, Actinic

Intervention

Drug:
• Tirbanibulin 2.5 mg ointment
Participants will apply tirbanibulin 2.5 mg ointment topically for 5 consecutive days over 25 square centimeters (cm^2) of the face or scalp.

Locations

Country	Name	City	State
Italy	Almirall Investigational Site 3	Rimini
Spain	Almirall Investigational Site 1	Valencia
Spain	Almirall Investigational Site 2	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Almirall, S.A.

Countries where clinical trial is conducted

Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment Satisfaction Questionnaire for Medication Version 9 (TSQM-9) Total Score at Day 57	TSQM-9 is a 9-item clinically validated psychometric instrument developed from the TSQM 1.4. In this self-administered questionnaire the 5 items associated with side effects related to the medication were excluded. The TSQM-9 global total scores vary from 0 to 100 with higher score indicating higher treatment satisfaction.	At Day 57
Secondary	Change from Baseline in Skindex-16 at Day 57	Skindex-16 is used for participants to rate skin conditions that have occurred within the previous week. It is a short 16-item patient-completed assessment that are classified into three domains: symptoms [four items, 1-4], emotions, [seven items, 5-11] and functioning [five items, 12-16]. All items are scored on a seven-point numerical analogue scales (0=never bothered to 6=always bothered). The potential global score is the average of all 16 items ranging from 0 (best HRQoL) to 96 (worst HRQoL). Each item is then transformed to a linear scale from 0 (never bothered) to 100 (always bothered). The higher the score, the more severe is the impairment.	Baseline, Day 57
Secondary	Organoleptic Properties of Tirbanibulin Assessed on a Likert Scale at Day 8	Likert scale is an instrument used to measure the individual's degree of agreement and disagreement with a variety of statements about some attitude, options, or their feelings. In this study, the product's organoleptic properties are evaluated with Likert scale. The questionnaire is built with questions related to the product's characteristics namely appearance, color, convenience, texture, smell, and the feelings experienced during drug application. The Likert scale offers 7 possible answers, from "totally agree" to "totally in disagreement."	At Day 8
Secondary	Treatment Satisfaction Questionnaire for Medication Version 1.4 (TSQM 1.4) Total Score at Day 57	TSQM 1.4 is a 14-item robust instrument that psychometrically evaluates the treatment satisfaction of the administered medication. The instrument is designed with 4 scales consisting of 14 questions. These 14 questions were derived from an original set of 55 questions extracted from exhaustive literature review and treatment groups through multistep iterative process. The 4 scales focused on efficacy (questions 1 to 3), side effects (questions 4 to 8), convenience (questions 9 to 11) and global satisfaction (questions 12 to 14). The global total score ranges from 0 - 100, where lower scores imply less satisfaction whilst higher scores imply higher satisfaction.	At Day 57
Secondary	Participant Treatment Preference Assessed Through Question 1 to Question 9 of the Expert Panel Questionnaire (EPQ) at Day 57		At Day 57
Secondary	Percentage of Participants with Complete (100%) Clearance of all Lesions Within the Application Area at Day 57		At Day 57
Secondary	Percentage of Participants with Partial Clearance, defined as a (Reduction of at least 75%) of Lesions Within the Application Area at Day 57	The lesions in the identified treatment area will be classified based on Olsen characterization. Classification of AK lesions according to Olsen grade of baseline lesions: Olsen Grade I: Early AK appear as single or few, differently sized, rough, blurred, less visible than palpable, red, rough spots or very flat, non-edged plaques which reach into the reddish color; Olsen grade II describes advanced AK as clearly visible and palpable, flat, and irregularly raised, with sharp or blurred boundaries, red, rough keratinized surface. If the surface is more strongly keratinized, the AK can also be white, yellow, or light brown. After scratching effects, a black or blue-black shade may appear; Olsen grade III denotes "late" AK that have existed for a longer period of time and are firmly anchored on the lower surface, with an irregular, humpy surface, also wart-like and of different colors (white, brown, black).	At Day 57
Secondary	Median Number of Old and New AK Lesions at Day 57		At Day 57
Secondary	Number of Lesions Classified Based on Olsen Characterization	The lesions in the identified treatment area will be classified based on Olsen characterization. Classification of AK lesions according to Olsen grade of baseline lesions: Olsen Grade I: Early AK appear as single or few, differently sized, rough, blurred, less visible than palpable, red, rough spots or very flat, non-edged plaques which reach into the reddish color; Olsen grade II describes advanced AK as clearly visible and palpable, flat, and irregularly raised, with sharp or blurred boundaries, red, rough keratinized surface. If the surface is more strongly keratinized, the AK can also be white, yellow, or light brown. After scratching effects, a black or blue-black shade may appear; Olsen grade III denotes "late" AK that have existed for a longer period of time and are firmly anchored on the lower surface, with an irregular, humpy surface, also wart-like and of different colors (white, brown, black).	Baseline (Day 0) and Day 57
Secondary	Noninvasive Imaging (Subclinical Lesions Response) with Reflectance Confocal Microscopy (RCM)	RCM is a noninvasive imaging device that can be used to monitor the severity of inflammatory skin disorders without the need for a biopsy. RCM can visualize cells with a resolution comparable to a light microscope, allowing the investigators to identify the degree of inflammation and damage to the skin. An overall disease severity score ranging from 0-3 (0=none, 1=mild, 2= moderate, 3=severe) will use aggregates of the following features: Spongiosis, Parakeratosis, Epidermal thickness, Quality of honeycomb structure of the stratum spinosum, Appearance of the dermal-epidermal junction, Appearance of the superficial dermis, Recognition of the dermal papilla, Caliber of blood vessels, Presence of inflammatory cells, Grading will be scored (0=none, 1=mild, 2= moderate, 3=severe), a greater numerical score indicates more advanced disease.	Baseline (Day 0), Day 8, Day 15, Day 29, and Day 57
Secondary	Noninvasive Imaging (Subclinical Lesions Response) with Optical Coherence Tomography (OCT)	OCT is a noninvasive imaging device that can be used to monitor the severity of inflammatory skin disorders without the need for a biopsy. OCT can detect deep structures in the skin, identify areas of inflammation, and determine the thickness of the skin. These measures will be consolidated to a severity score ranging 0-3, (0= no disease, 3= severe disease) and will be tracked throughout the duration of the study. The following features will be aggregated to form an Optical Coherence Tomography-severity-score: Change in the epidermal thickness; Changes in anatomy or appearance of the dermo-epidermal junction and the dermis; Changes in vascular flow patterns, including the number and density of vessels in skin using the dynamic feature of Optical Coherence Tomography; Grading will be scored 0=none, 1=mild, 2= moderate, 3=severe.	Baseline (Day 0), Day 8, Day 15, Day 29, and Day 57
Secondary	Physician Outcomes Assessed Through Question 1 to Question 10 of the EPQ		At Day 57
Secondary	Number of Participants with Adverse Events and Severity of Adverse Events		From start of study administration up to Day 57