Efficacy, Safety and Pharmacokinetics of Oral LDE225 in Treatment of Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS)

NCT01350115 | Completed Phase 2 Results

• 2 other identifiers: CLDE225B22092010-023819-34
• Study Type: interventional
• Target: 10
• Locations: 4 countries
• Sites: 6

Brief Summary

This was a phase II, double-blind, randomized, proof-of-concept, dose-ranging trial evaluating the efficacy, safety and pharmacokinetics of oral LDE225 in treatment of adult patients with NBCCS. This was an exploratory study designed to demonstrate preliminary efficacy of LDE225 in this indication. This study included a Screening period of approximately 4 weeks, treatment period duration of 12 weeks with initial follow-up of approximately 6-8 weeks followed by a long-term follow-up period.

Conditions

Basal Cell Carcinoma; Gorlin Syndrome; Nevoid Basal Cell Carcinoma Syndrome

Keywords

Basal Cell Carcinoma; Gorlin Syndrome,; Gorlin-Goltz Syndrome,; Basal Cell Nevus Syndrome,; Nevoid Basal Cell Carcinoma Syndrome,; Basal Cell Carcinoma Nevus Syndrome; Smo inhibitor,; Hedgehog pathway inhibitor; BCCs

Outcome Measures

Primary Outcomes (1)

• Clinical Clearance Assessment of Main Target Basal Cell Carcinomas (BCCs)

  The clinical response of the main target (and secondary target, as appropriate) BCC(s) to treatment was evaluated using the following 6-point scale comparing the assessment at the visit to the clinical presentation at Baseline: 0 = Worsening, 1 = No change, 2 = Slight clearance (1-25% improvement), 3 = Moderate clearance (26-75% improvement), 4 = Marked clearance (76-99% improvement),5 = Complete clearance (100% improvement) Complete clearance was defined as no clinical residual signs of carcinoma, as evaluated by the Investigator at a post-Baseline visit, with the exception of post-inflammatory changes such as minimal residual erythema or residual hyper-pigmentation or hypo-pigmentation or residual scarring.

  Day 113

Secondary Outcomes (2)

• Histological Clearance Assessment of Main Target BCCs

  day 113

• Measure: Disease Burden by BCC Tumor Counts

  Baseline, day 85, and day 113

Study Arms (2)

LDE225

ACTIVE COMPARATOR

Participants received 400 mg once daily.

Drug: LDE225

Placebo

PLACEBO COMPARATOR

Participants received matching placebo.

Drug: Placebo

Interventions

LDE225 DRUG

supplied as 100 mg capsules

LDE225

Placebo DRUG

supplied in capsules

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with multiple basal cell carcinomas (at least two) and typical presentation of NBCCS.
• Female patients must be women of non-childbearing potential (WONCBP).

You may not qualify if:

• Use of any topical treatment to treat BCCs, including prescription and over the counter in the 4 weeks prior to first dose of study drug.
• Use of photodynamic therapy (PDT), radiation or systemic treatment known to affect BCCs or neoplasm in the 12 weeks prior to first dose of study drug.
• Patients receiving medications that are recognized to cause rhabdomyolysis or patients with a prior history of rhabdomyolysis.
• Patients with a histologically confirmed diagnosis of locally advanced or metastatic BCC.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (6)

Novartis Investigative Site

Vienna, A-1090, Austria

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Markham, Ontario, L3P 1A8, Canada

Location

Novartis Investigative Site

Waterloo, Ontario, N2J 1C4, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H2K 4L5, Canada

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

MeSH Terms

Conditions

Carcinoma, Basal Cell; Basal Cell Nevus Syndrome

Interventions

sonidegib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell; Odontogenic Cysts; Jaw Cysts; Bone Cysts; Cysts; Neoplastic Syndromes, Hereditary; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Jaw Diseases; Stomatognathic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2011
• First Posted: May 9, 2011
• Study Start: April 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: October 19, 2015
• Results First Posted: October 19, 2015

Record last verified: 2015-09

Locations

CA (3); AU (1); DE (1); BE (1)