Evaluation of the Safety and Efficacy of Imiquimod Gel Versus Imiquimod Cream in the Treatment of Actinic Keratosis in Adult Patients

The primary objective of this study is to evaluate the **efficacy** of Keramod® Gel (imiquimod 5%, Gel) compared to Aldara® Cream (imiquimod 5%, cream) in the treatment of **actinic keratosis** (AK) by assessing the complete clearance of AK lesions at week 24 from the first treatment dose. This is clinically relevant as achieving complete clearance of lesions is a critical endpoint in the management of AK, potentially reducing the risk of progression to squamous cell carcinoma.

Secondary objectives include:

• Evaluating the reduction in the number of AK lesions from baseline to weeks 8 and 16 in subjects treated with Keramod® Gel versus Aldara® Cream.
• Assessing the efficacy of Keramod® Gel versus Aldara® Cream in terms of complete clearance of AK lesions (100% reduction of lesions) at weeks 8 and 16.
• Evaluating the safety of the topical treatment of Keramod® Gel versus Aldara® Cream.
• Assessing the treatment tolerance and patient acceptance of the treatment in subjects treated with Keramod® Gel versus Aldara® Cream.
• Evaluating the adherence to treatment in subjects treated with Keramod® Gel versus Aldara® Cream.

The clinical trial focuses on evaluating the efficacy of Keramod® Gel (imiquimod 5%, Gel) versus Aldara® Cream (imiquimod 5%, cream) in the treatment of **actinic keratosis**. The study population includes both male and female participants aged over 18 years, encompassing a diverse range of skin types and races, provided that the skin pigmentation allows for discernment of the lesions. Participants must be in good health, confirmed by medical history and physical examination, and free of any clinically significant disease or condition, other than actinic keratosis, that could interfere with the study evaluations. The trial includes individuals with 4 to 8 clinically diagnosed, non-hyperkeratotic, non-hypertrophic actinic keratosis lesions within a 25 cm² contiguous treatment area on either the face or balding scalp. Women participants are required to be either one year postmenopausal, surgically sterile, or agree to use a medically accepted form of birth control. The trial population was selected based on their ability to understand and fulfill the study requirements, and all participants provided informed consent. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed as an exploratory, multicenter, randomized, open-label with blind evaluation, active-controlled study. The primary objective is to evaluate the **efficacy** of Keramod® Gel (imiquimod 5%, Gel) compared to Aldara® Cream (imiquimod 5%, Cream) in the treatment of **actinic keratosis** in adults. The trial aims to assess the complete clearance of actinic keratosis lesions at week 24 from the first treatment dose. The study will involve participants who have 4 to 8 clinically diagnosed, non-hyperkeratotic, non-hypertrophic actinic keratosis lesions within a 25 cm² contiguous treatment area on either the face or balding scalp. Participants must be over 18 years of age, in good health, and free of any significant findings in the potential application site area.

The trial will span an estimated duration from January 20, 2020, to August 31, 2025. Participants will be involved for a maximum treatment period of 16 weeks, with the study structured into two treatment cycles. The sequence of study visits includes an initial screening visit to confirm eligibility, followed by treatment visits at weeks 8 and 16, and a final evaluation at week 24. The primary endpoint is the complete clearance of actinic keratosis lesions, defined as a count of zero lesions at week 24. Secondary endpoints include partial and complete clearance rates at the end of the first and second cycles, tolerance and acceptability of the treatment, adherence evaluation, and the rate of subjects completing one or two treatment cycles. The severity and frequency of associated adverse events will also be monitored.

Participants are expected to comply with contraception requirements and must provide informed consent. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or the occurrence of adverse events that necessitate discontinuation. The trial is not categorized as low intervention and is classified as a phase 4 study, focusing on the safety, efficacy, tolerance, and adherence of Keramod® Gel compared to Aldara® Cream.

The clinical trial involves the evaluation of two **imiquimod**-based treatments for actinic keratosis. The experimental medication, **Keramod® gel**, is formulated as a gel containing **imiquimod** at a concentration of 50 mg/g. The gel is intended for **cutaneous use** and is applied directly to the skin. The maximum daily dose is 250 mg, with a total treatment period not exceeding 16 weeks. The gel is manufactured by Laboratorios Ojer Pharma S.L. and is of chemical origin. Participants are instructed to apply the gel as per the dosing schedule provided, and compliance is monitored throughout the study.

The comparator treatment in this study is **ALDARA 5% cream**, which also contains **imiquimod** at a concentration of 50 mg/g. Similar to the experimental treatment, the cream is for **cutaneous use** and is applied to the skin. The maximum daily dose is 250 mg, with a treatment duration of up to 16 weeks. ALDARA 5% cream is produced by Viatris Healthcare Ltd and is also of chemical origin. Participants are required to adhere to the application schedule, and their compliance is monitored to ensure accurate assessment of the treatment's efficacy.

Both treatments are designed to be applied directly to the affected areas of the skin, and the study aims to compare their safety and efficacy in achieving complete clearance of actinic keratosis lesions. The trial is conducted in an open-label format with blind evaluation to ensure unbiased assessment of outcomes. Participants' adherence to the treatment regimen is closely monitored to maintain the integrity of the study results.

The efficacy of the investigational product, Keramod® Gel (imiquimod 5%, Gel), will be assessed in comparison to the reference product, Aldara® Cream (imiquimod 5%, Cream), in the treatment of actinic keratosis (AK) in adults. The primary endpoint for evaluating efficacy is the complete clearance of AK lesions, defined as a count of zero AK lesions, at week 24 following the first treatment dose. Secondary endpoints include the partial and complete clearance rate of AK lesions at the end of the first and second treatment cycles, specifically at week 8 and week 16. Additional secondary endpoints involve the assessment of treatment tolerance and acceptability through a Treatment Tolerance and Satisfaction Questionnaire, evaluation of adherence via a Treatment Adherence Questionnaire, and the rate of subjects completing one or two treatment cycles. The severity and frequency of associated adverse events or serious adverse events (AEs/SAEs) will also be monitored.