ong-term clinical safety study to evaluate the risk of actinic keratosis progressing to skin cancer following treatment of the face or scalp with tirbanibulin 10 mg/g ointment and in comparison to diclofenac 3% gel in adult patients. Tirbanibulin and diclofenac are used to treat adults with actinic keratosis on the face and scalp. Actinic keratosis is a precancerous, abnormal skin growth that develops after too much exposure to sunlight.

Phase 1

Conditions: Actinic Keratosis on the Face or Scalp
MedDRA version: 20.0Level: PTClassification code 10000614Term: Actinic keratosisSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: EUCTR2021-004349-18-FR

Lead Sponsor: Almirall, S.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 540

Inclusion Criteria

1. Male or female and =18 years old.
2. A TF on the face or scalp (excluding lips, eyelids, ears, and inside the nostrils), that:
• Is a contiguous area measuring 25 cm2,
• Contains 2 to 8 clinically typical, visible, and discrete AK lesions, and
• Has an overall clinical picture that is consistent with Olsen grade 1.
3. If a WOCBP, ie, 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:
• Have a negative urine pregnancy test using a highly sensitive method at screening and on Day 1 prior to treatment administration.
• Be using effective methods of birth control.
• Agree to have pregnancy tests while in the study and at the end of the study (according to the Schedule of Assessments in Table 1).
4. Patients should be willing to avoid sunlight or UV light exposure, including the use of tanning beds, to the face or scalp during the study.
5. Patients 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 350

Exclusion Criteria

1. The location of the TF is:
a) On any location other than the face or scalp.
b) Within 5 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.
2. Presence in the TF of:
a) Clinically atypical and/or rapidly changing AK lesions
b) Hyperkeratotic or hypertrophic lesions, recalcitrant disease (had cryosurgery onc2 previous occasions), and/or cutaneous horn.
c) Confluent AK lesions (ie, non-discrete lesions, as per inclusion criterion 2).
d) Persisting AK lesions at the screening visit following topical treatment with diclofenac sodium 3% gel.
3. 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.
4. 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.
5. Immunocompromised patients, including patients with a history of chronic systemic lymphoma or chronic myeloid leukaemia, or organ transplant recipients.
6. Any other dermatological disease that causes difficulty with examination within the treatment area.
7. Anticipated need for inpatient hospitalization or inpatient surgery during the study.
8. Previous treatment with tirbanibulin 10 mg/g ointment in the selected TF.
9. Treatment with 5-fluorouracil, imiquimod, ingenol mebutate, diclofenac, photodynamic therapy, or other topical treatments for AK within the TF or within 2 cm of the TF, within 8 weeks prior to the Screening Visit.
10. Use of the following therapies and/or medications within 4 weeks prior to the Screening Visit:
a) Treatment with cytotoxic drugs (eg, cyclophosphamide, vinblastine, chlorambucil, methotrexate)
b) Treatment with systemic medications that modulate and/or suppress the immune system (eg, cyclosporine, prednisone, methotrexate, alefacept, infliximab, interferons or interferon inducers)
c) Use of systemic retinoids (eg, isotretinoin, acitretin, bexarotene)
11. Use of the following therapies and/or medications within 2 weeks prior to the Screening
Visit:
a) Cosmetic or therapeutic procedures (eg, use of liquid nitrogen, surgical excision, curettage, dermabrasion, medium or greater depth chemical peel, laser resurfacing) within the TF or within a 2 cm margin of the selected TF.
b) Acid-containing therapeutic products (eg, salicylic acid or fruit acids, such as alpha and beta-hydroxyl acids and glycolic acids), topical retinoids, or light chemical peels within the TF or within a 2 cm margin of the selected TF.
c) Topical steroids within the TF or within a 2 cm margin of the selected TF.
d) Artificial tanners within the TF or within a 5 cm margin of the selected TF.
12. History of sensitivity and/or allergy to any of the ingredients in the study medications to tirbanibulin, diclofenac, or nonsteroidal anti-inflammatory drugs (ie, NSAIDs).
13. A skin disease (eg, atopic dermatitis, psoriasis, eczema) or condition (eg, scarring, open wounds) that, in the opinion of the Investigator, might interfere with the study conduct or evaluations, or which exposes the patient to unacceptable risk by study participation.
14. Significant uncontrolled or unstable medical diseases or conditions that, in the opinion of the Investigator, would

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the incidence of biopsyconfirmed invasive SCC in the selected TF after administration of topical tirbanibulin 10 mg/g ointment or diclofenac sodium 3% gel over the 3-year study period.;Secondary Objective: To evaluate the safety of topical tirbanibulin 10 mg/g ointment and diclofenac sodium 3% gel over the 3-year study period;Primary end point(s): Proportion of patients with histologically confirmed invasive SCC in the TF over the 3-year study period.;Timepoint(s) of evaluation of this end point: Please refer to E.5.1

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • AEs and SAEs over 3 years<br>• Proportion of patients with any other skin cancer (other than SCC) in the TF over the 3-year study period.<br>• Time to occurrence of invasive SCC from baseline in the TF.<br>• Proportion of patients requiring rescue treatment after 1 treatment course.<br>• Proportion of patients requiring rescue treatment at any time during the study.<br>• Proportion of patients with no lesions after treatment of the first recurrence with tirbanibulin during the first 52 weeks.<br>• Other safety assessments (vital signs, PE) over 3 years;Timepoint(s) of evaluation of this end point: Please refer to E.5.2