Efficacy, Safety and Tolerability of Topically Applied LDE225 Cream (Hedgehog Pathway Inhibitor) in Adult Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS)

Study Overview
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Brief Summary
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This 22 week study will assess the efficacy, safety, and tolerability of LDE225 versus vehicle when applied topically to basal cell carcinoma (BCC) in patients with NBCCS. Patients will treat multiple BCCs for up to 12 weeks. Treatment success is defined as complete clinical clearance and complete histological clearance in BCCs.

Official Title
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A Randomized, Double-blind, Vehicle-controlled, Multicenter Trial of Topically Administered LDE225 Cream (0.75% Bid) to Evaluate Clearance of Basal Cell Carcinoma in Adult Patients With Nevoid Basal Cell Carcinoma Syndrome

Conditions
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Basal Cell Carcinoma

Intervention / Treatment
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* Drug: LDE225B
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult greater than 18 years old, male or female. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study. Typical presentation of NBCCS in the opinion of the investigator At least one of the major clinical criteria of NBCCS. Multiple BCCs during the screening period Exclusion Criteria: Any concomitant dermatological disease that could confound the evaluations, based on the discretion of the investigator. Prior exposure to LDE225. Use of systemic treatment for BCC in the 4 weeks prior to Baseline. Use of topical treatment or photodynamic therapy (PDT) in the 12 weeks prior to Baseline. Use of other investigational drugs at Baseline, or within 30 days or 5 half-lives prior to Baseline, whichever is longer. Clinically significant medical condition, as per judgment of the investigator. History of hypersensitivity to any of the ingredient of the study drug. Pregnant or nursing (lactating) women Women of child-bearing potential and fertile males, UNLESS they are using two birth control methods Other protocol-defined inclusion/exclusion criteria may apply

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LDE225 0.75% cream<br> | Drug: LDE225B<br>* Cream, 2x daily<br>|
| Placebo Comparator: Vehicle<br> | Drug: Vehicle<br>* cream, 2x daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate superiority of topical LDE225 versus vehicle in terms of treatment success in patients with NBCCs. Measure: Complete clinical clearance and complete histological clearance of BCCs |  | 4 weeks after LDE225 treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety of topical treatment with LDE225, compared to vehicle. Measure: Reported systemic adverse events in patients with NBCCS |  | Treatment phase and up to 4 weeks after LDE225 treatment | 
| To evaluate the local tolerability of topical treatment with LDE225, compared to vehicle. Measure:Reported local adverse events in patients with NBCCS |  | Treatment phase and up to 4 weeks after LDE225 treatment | 
| To assess the rate of complete clinical clearance of BCCs in patients with NBCCS. Measure: No clinical residual signs of carcinoma |  | 4 weeks after LDE225 treatment | 
| To assess the rate of complete histological clearance of BCCs in patients with NBCCS. Measure: No residual tumor tissue |  | 4 weeks after LDE225 treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Basal Cell Nevus Syndrome, BCNS, Hedgehog pathway inhibitor, topical, Smoothened, Basal cell carcinoma, Nevoid Basal Cell Carcinoma Syndrome, NBCCS, Gorlin syndrome, Gorlin-Goltz Syndrome