Phase 3 Study of Patidegib Gel 2% for Basal Cell Carcinoma Reduction in Gorlin Syndrome Patients

The primary objective of this study is to assess the **efficacy** of Patidegib Gel 2% when applied twice daily to the face of subjects with **Gorlin Syndrome**. This is clinically relevant as Gorlin Syndrome is characterized by the development of multiple basal cell carcinomas (BCCs), and effective management can significantly reduce disease burden and improve patient outcomes.

Secondary objectives include:

• To assess the **safety** and **tolerability** of Patidegib Gel 2% in subjects treated twice daily for 12 months.

The clinical trial involves a total of **96 participants** diagnosed with **Gorlin Syndrome**, a genetic condition characterized by the development of multiple basal cell carcinomas (BCCs). The study population includes both male and female subjects, aged 18 years and older, who have been confirmed to possess a PTCH1 mutation. Participants were selected based on their ability to meet specific criteria, including having at least 10 BCCs on the face at the time of randomization. The trial requires participants to abstain from using any non-study topical medications on their facial skin, except those prescribed by the investigator, to ensure the efficacy of Patidegib Gel 2% is accurately assessed. The study population is considered vulnerable, highlighting the importance of careful monitoring and ethical considerations throughout the trial.

The clinical trial is designed as a **randomized**, **double-blind**, vehicle-controlled, Phase 3 study to evaluate the efficacy and safety of Patidegib Gel 2% in reducing the disease burden of persistently developing basal cell carcinomas (BCCs) in subjects with **Gorlin Syndrome**. The trial will involve two arms: one receiving Patidegib Gel 2% and the other receiving a vehicle gel, both applied topically to the face twice daily. The primary endpoint is the number of new BCCs at Month 12, assessed by the CPRB. Secondary endpoints include the number of new surgically eligible BCCs, changes in lesion symptoms, and quality of life measures over the same period.

The trial is expected to commence recruitment on March 1, 2024, and conclude by January 29, 2026. Participants will be involved for a maximum of 12 months, with study visits scheduled at baseline, monthly follow-ups, and an end-of-study visit at Month 12. The inclusion criteria require participants to be at least 18 years old, have a confirmed PTCH1 mutation, and present with at least 10 BCCs on the face at baseline. Participants must also agree to abstain from using non-study topical medications on their facial skin during the trial, except as prescribed by the investigator.

Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or the occurrence of adverse events that, in the investigator's opinion, warrant discontinuation. The trial will ensure rigorous monitoring of safety and efficacy, with adverse events and local tolerability assessments conducted throughout the study duration. The study aims to provide valuable insights into the potential of Patidegib Gel 2% as a therapeutic option for managing BCCs in individuals with Gorlin Syndrome.

The clinical trial involves the use of **Patidegib Gel**, an experimental medication formulated as a gel for **topical application**. The active substance in Patidegib Gel is **patidegib hydrochloride isopropanolate**, a chemical compound. The gel is applied twice daily to the face of subjects diagnosed with Gorlin syndrome, with a maximum daily dose of 1 gram. The treatment period extends up to 12 months. Patidegib Gel is manufactured by SOL-GEL TECHNOLOGIES LTD. and is identified by the product number PRD10934043. The primary objective of the trial is to evaluate the efficacy of Patidegib Gel 2% in reducing the disease burden of persistently developing basal cell carcinomas in subjects with Gorlin syndrome.

In addition to the experimental treatment, the study employs a **Vehicle Gel** as a **placebo** control. The Vehicle Gel is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of which treatment is being administered. The Vehicle Gel is applied in the same manner as the Patidegib Gel, with the same frequency and dosage, to ensure consistency in the administration process. The use of a placebo control is critical in assessing the true efficacy of the experimental treatment by providing a baseline for comparison.

The efficacy of Patidegib Gel 2% in reducing the disease burden of persistently developing **Basal Cell Carcinomas (BCCs)** in subjects with Gorlin Syndrome will be assessed through a multicenter, randomized, double-blind, vehicle-controlled, Phase 3 study. The primary endpoint for evaluating efficacy is the number of new BCCs at Month 12 in the two arms (Patidegib Gel 2% and vehicle) when applied twice daily to the face of subjects with Gorlin Syndrome, as assessed by the CPRB. Secondary endpoints include the number of new surgically eligible BCCs (nSEBs) at Month 12, changes from baseline to Month 12 in the Advanced Basal Cell Carcinoma Index (aBCCdex) lesion symptoms scale score, and changes in confirmed BCCs lesion diameter. Additional secondary endpoints involve the proportion of surgically eligible BCCs (SEBs) and nSEBs assessed as resolved by Month 12, the proportion of SEBs and nSEBs per subject that have regressed by Month 12, and the proportion of subjects developing two or more facial new BCCs at Month 12. Other measures include changes in the total number of confirmed BCCs from baseline to Month 12, changes in the Skin Cancer Index quality of life questionnaire score, and adverse events (AEs), including serious adverse events (SAEs) occurring at any time during the study. Investigator Dermal Safety and Local Tolerability Assessments score, changes from baseline to Month 12 in Patient Global Impression in disease Severity (PGI-S), and changes in Patient Global Impression of Change in clinical status (PGI C) at Month 12 will also be evaluated. The time to first new BCC and skin pain and peak pruritus scores as reported by the subject on a numeric rating scale are included in the efficacy assessments.