A Study of Tirbanibulin Ointment and Diclofenac Sodium Gel for the Treatment of Adult Participants With Actinic Keratosis on the Face or Scalp

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the incidence of biopsy confirmed invasive squamous cell carcinoma (SCC) in the selected treatment field (TF) after administration of topical tirbanibulin 10 milligram (mg)/gram (g) ointment or diclofenac sodium 3 percent (%) gel over the 3-year study period.

Official Title
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A Phase 4, Multi-centre, Randomized, Evaluator-blinded, Active-controlled Study to Determine the Incidence of Squamous Cell Carcinoma and Evaluate the Long-term Safety of Tirbanibulin 10 mg/g Ointment and Diclofenac Sodium 3% Gel for the Treatment of Adult Patients With Actinic Keratosis on the Face or Scalp

Conditions
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Keratosis, Actinic

Intervention / Treatment
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* Drug: Tirbanibulin (Klisyri®) 10 mg/g ointment
* Drug: Diclofenac Sodium 3% Gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A treatment field (TF) on the face or scalp (excluding lips, eyelids, ears, and inside the nostrils), that: a) is a contiguous area measuring 25 cm^2, b) contains 2 to 8 clinically typical, visible, and discrete actinic keratosis (AK) lesions, and c) has an overall clinical picture that is consistent with Olsen grade 1 If a women of child-bearing 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), she must: a) Have a negative urine pregnancy test using a highly sensitive method at screening and on Day 1 prior to treatment administration. b) Be using effective methods of birth control. c) Agree to have pregnancy tests while in the study and at the end of the study Participants should be willing to avoid sunlight or ultraviolet (UV) light exposure, including the use of tanning beds, to the face or scalp during the study Participants should have the ability to understand the purpose and risks of the study, willingness and ability to comply with the protocol, and provide written informed consent in accordance with institutional and regulatory guidelines Exclusion Criteria: The location of the TF is: a) on any location other than the face or scalp. b) within 5 centimeters (cm) of an incompletely healed wound. c) Within 10 cm of a suspected basal cell carcinoma (BCC) or other neoplasm. d) on the lips, eyelids, ears, or inside the nostrils, periorbital, perioral, or the skin surrounding the nostrils Presence in the TF of: a) clinically atypical and/or rapidly changing AK lesions b) hyperkeratotic or hypertrophic lesions, recalcitrant disease (had cryosurgery on 2 previous occasions), and/or cutaneous horn. c) confluent AK lesions (that is, non-discrete lesions, as per inclusion criterion 2). d) Persisting AK lesions at the screening visit following topical treatment with diclofenac sodium 3 percent (%) gel History of any malignant skin tumour in the TF or history of skin tumour in any region of the body which has metastasized or in which metastasis within the study period is likely History of any malignant tumour with systemic antitumor treatment (including radiotherapy) within 12 weeks prior to the Screening Visit or systemic antitumor treatment is expected while on the study Immunocompromised participants, including participants with a history of chronic systemic lymphoma or chronic myeloid leukaemia, or organ transplant recipients

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tirbanibulin 10 milligram per gram (mg/g) ointment<br>Participants will apply tirbanibulin ointment 10 mg/g once daily to the treatment field (TF) for 5 consecutive days beginning Day 1. At subsequent visits, participants will have the option of an additional 5-day course(s) (with at least 16 weeks between starting date of treatment courses) at the discretion of the investigator if actinic keratosis (AK) lesions are present in the TF and physical treatment is not appropriate. | Drug: Tirbanibulin (Klisyri®) 10 mg/g ointment<br>* Participants will apply tirbanibulin 10 mg/g ointment topically for 5 days over 25 cm^2 of the face or scalp with Actinic Keratosis (AK).<br>* Other names: Klisyri®;|
| Active Comparator: Diclofenac Sodium 3% Gel<br>Participants will apply diclofenac sodium 3% gel twice daily to the TF for 60 to 90 days beginning Day 1, with the option of further courses every 6 months (with at least 6 months between starting date of treatment courses) if lesions are found to be present in the TF at follow up visits and physical treatment is not appropriate. | Drug: Diclofenac Sodium 3% Gel<br>* Participants will apply diclofenac dodium 3% gel twice daily for 60 to 90 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Histologically Confirmed Invasive Squamous Cell Carcinoma (SCC) in the Treatment Field (TF) | Percentage of participants with histologically confirmed invasive SCC in the TF will be reported as assessed by dermoscopy. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) | An Adverse Event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered an Investigational Product. An AE does not necessarily have a causal relationship with the medicinal product. | Up to 3 years | 
| Number of Participants With Serious Adverse Events (SAEs) | 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). | Up to 3 years | 
| Percentage of Participants With any Other Skin Cancer (Other Than SCC) in the TF | Percentage of participants with any other skin cancer (other than SCC) in the TF will be reported. | Up to 3 years | 
| Time to Occurrence of Invasive SCC From Baseline in the TF | Time to occurrence of invasive SCC from baseline in the TF will be reported. | Up to 3 years | 
| Percentage of Participants Requiring Rescue Treatment After 1 Treatment Course | Percentage of participants requiring rescue treatment after 1 treatment course will be reported. | Up to 3 years | 
| Percentage of Participants Requiring Rescue Treatment at Any Time During the Study | Percentage of participants requiring rescue treatment at any time during the study will be reported. | Up to 3 years | 
| Percentage of Participants With no Lesions After Treatment of the First Recurrence With Tirbanibulin During the First 52 Weeks | Percentage of participants with no lesions after treatment of the first recurrence with tirbanibulin during the first 52 weeks will be reported. | Up to Week 52 | 
| Number of Participants With Vital Signs Abnormalities | Number of participants with vital signs (including measurement of heart rate, respiratory rate, systolic and diastolic blood pressure and tympanic temperature) will be reported. | Up to 3 years | 
| Number of Participants With Physical Examination Abnormalities | Number of participants with physical examination abnormalities (height, weight and an assessment of head, eyes, ears, nose and throat, integumentary/dermatological, gastrointestinal, cardiovascular, respiratory, musculoskeletal, and neurological systems) will be reported. | Up to 3 years |