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| ID | Type | Description | Link |
|---|---|---|---|
| EudraCT 2008 005506-40 |
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Part I was a double-blind, randomized, vehicle-controlled Proof of Concept (PoC) study to evaluate the safety, local tolerability, pharmacokinetics and pharmacodynamics of multiple topical administrations of LDE225 (a specific Smoothened inhibitor) on skin basal cell carcinomas in Gorlin's syndrome patients.
Following a 21-day screening period, patients were exposed to multiple doses of topically applied LDE225 twice daily for 4 weeks in a double-blind manner. The patients returned weekly for visits where each BCC was clinically evaluated and digital photographs taken. Local safety and tolerability was also assessed. After the last application of treatment, biopsies were taken from treated (both vehicle and LDE225) BCCs (three per patient) for histology, biomarker evaluation and for pharmacokinetics (skin exposure). In addition, a biopsy from LDE225-treated uninvolved perilesional skin was taken for pharmacokinetic evaluation. In total, 4 biopsies were taken: 2 for histology and biomarker and 2 for PK.
Part II of this study consisted of a 21-day screening period, a baseline period (directly before commencing the treatment period) and a treatment period of 6 or 9 weeks, depending on randomization. A clinical assessment was performed on site on the last treatment day and if a full clinical response had been observed, approximately 3 weeks after the last treatment an excision of the BCC(s) would have been performed. The study completion visit occurred either 1 week after the excision (when this visit was planned) or 1 week after the last treatment. For a subset of patients, skin biopsies were collected on the last treatment day and an excision of a BCC was also performed at that same visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LDE225 (applied in parallel with vehicle) [Part I] | Active Comparator | Participants were exposed to both topically applied 0.75% LDE225 cream and LDE225 vehicle cream twice daily for 28 days where each treatment was randomized to two different test areas on each participant. |
|
| Vehicle cream (applied in parallel with LDE225 [Part I] | Placebo Comparator | Participants were exposed to both topically applied 0.75% LDE225 cream and LDE225 vehicle cream twice daily for 28 days where each treatment was randomized to two different test areas on each participant. |
|
| LDE225 0.25% [Part II] | Active Comparator | Participants were exposed to topically applied 0.25% LDE225 cream twice daily for 6 weeks. |
|
| LDE225 0.75% [Part II] | Active Comparator | Participants were exposed to topically applied 0.75% LDE225 cream twice daily where some basal cell carcinomas (BCCs) were teated for 6 weeks and some BCCs were treated for 9 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vehicle | Drug | Placebo cream |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Clinical response parameters were defined as (i) complete response (i.e., there is no longer any visible evidence of a lesion consistent with BCC at this site), (ii) partial response (i.e., although a BCC still remains at this site, it has demonstrated a visible decrease in size compared with baseline), and (iii) no response / worsening (i.e., the BCC has not demonstrated any visible decrease in size compared with baseline). | 4 weeks, 6 weeks, 9 weeks |
| Number of Participants With at Least Partial Clinical Clearance (Part I) | Clinical response parameters were defined as (i) complete response (i.e., there is no longer any visible evidence of a lesion consistent with BCC at this site), (ii) partial response (i.e., although a BCC still remains at this site, it has demonstrated a visible decrease in size compared with baseline), and (iii) no response / worsening (i.e., the BCC has not demonstrated any visible decrease in size compared with baseline). | day 8, day 15, day 22, day 29 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Tumor Measurements (Part I) | Measurement of the tumor size, volume and color by standardized digital photography, using dermatoscopic, macroscopic and 3D images of the BCCs was done by participant where if a participant had more than one tumor, for each of these tumors, the change from baseline was calculated (% change). From these values, the mean was calculated to get only one result per participant. Then for all the participants (n=8 both for LDE and vehicle), the mean was calculated. Photographic analysis was conducted by QuantifiCare. The volume of a lesion was measured with a special device, the "3D LIFEVIZ Micro system", which uses a lens splitter to produce two images of the skin surface, captured at the same time, with viewing angle differences close to human vision. A stereovision algorithm is then applied to reconstruct and quantitatively analyze the skin surface in 3D. A negative change from baseline indicates improvement. |
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Inclusion Criteria:
- Patients with multiple basal cell carcinomas and Gorlin syndrome, or patients with multiple basal cell carcinomas and a mutation in the PTCH1 gene at chromosome 9q22.3
Exclusion Criteria:
Other protocol defined Incl./Excl. criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Graz | Austria | ||||
| Novartis Investigator Site |
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| ID | Title | Description |
|---|---|---|
| FG000 | All Part I Participants | Participants were exposed to both topically applied 0.75% LDE225 cream and LDE225 vehicle cream twice daily for 28 days where each treatment was randomized to two different test areas on each participant. LDE225 0.75% |
| FG001 | LDE225 0.25% [Part II] |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| LDE225 0.25% |
| Drug |
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| LDE225 0.75% | Drug |
|
| 4 weeks |
| Change From Baseline in Tumor Measurements (Part II) | Measurement of the tumor size, volume and color by standardized digital photography, using dermatoscopic, macroscopic and 3D images of the BCCs was done by participant where if a participant had more than one tumor, for each of these tumors, the change from baseline was calculated (% change). From these values, the mean was calculated to get only one result per participant. Then for all the participants (n=8 both for LDE and vehicle), the mean was calculated.. Photographic analysis was conducted by QuantifiCare. The volume of a lesion was measured with a special device, the "3D LIFEVIZ Micro system", which uses a lens splitter to produce two images of the skin surface, captured at the same time, with viewing angle differences close to human vision. A stereovision algorithm is then applied to reconstruct and quantitatively analyze the skin surface in 3D. A negative change from baseline indicates improvement. | 4 weeks, 6 weeks, 9 weeks |
| Change From Baseline in Tumor Measurements (by Tumor) (Part I) | Measurement of the tumor size, volume and color by standardized digital photography, using dermatoscopic, macroscopic and 3D images of the BCCs. Photographic analysis was conducted by QuantifiCare. The volume of a lesion was measured with a special device, the "3D LIFEVIZ Micro system", which uses a lens splitter to produce two images of the skin surface, captured at the same time, with viewing angle differences close to human vision. A stereovision algorithm is then applied to reconstruct and quantitatively analyze the skin surface in 3D. A negative change from baseline indicates improvement. | 4 weeks |
| Change From Baseline in Tumor Measurements (by Tumor) (Part II) | Measurement of the tumor size, volume and color by standardized digital photography, using dermatoscopic, macroscopic and 3D images of the BCCs. Photographic analysis was conducted by QuantifiCare. The volume of a lesion was measured with a special device, the "3D LIFEVIZ Micro system", which uses a lens splitter to produce two images of the skin surface, captured at the same time, with viewing angle differences close to human vision. A stereovision algorithm is then applied to reconstruct and quantitatively analyze the skin surface in 3D. A negative change from baseline indicates improvement. | 4 weeks, 6 weeks, 9 weeks |
| Vienna |
| Austria |
| Novartis Investigative Site | Zurich | Switzerland |
Participants were exposed to topically applied 0.25% LDE225 cream twice daily for 6 weeks. LDE225 0.25% |
| FG002 | LDE225 0.75% [Part II] | Participants were exposed to topically applied 0.75% LDE225 cream twice daily where some basal cell carcinomas (BCCs) were treated for 6 weeks and some BCCs were treated for 9 weeks. LDE225 0.75% |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Part I Participants | Participants were exposed to both topically applied 0.75% LDE225 cream and LDE225 vehicle cream twice daily for 28 days where each treatment was randomized to two different test areas on each participant. LDE225 0.75% |
| BG001 | LDE225 0.25% [Part II] | Participants were exposed to topically applied 0.25% LDE225 cream twice daily for 6 weeks. LDE225 0.25% |
| BG002 | LDE225 0.75% [Part II] | Participants were exposed to topically applied 0.75% LDE225 cream twice daily where some basal cell carcinomas (BCCs) were treated for 6 weeks and some BCCs were treated for 9 weeks. LDE225 0.75% |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of BCCs With Complete and at Least Partial Clinical Clearance | Clinical response parameters were defined as (i) complete response (i.e., there is no longer any visible evidence of a lesion consistent with BCC at this site), (ii) partial response (i.e., although a BCC still remains at this site, it has demonstrated a visible decrease in size compared with baseline), and (iii) no response / worsening (i.e., the BCC has not demonstrated any visible decrease in size compared with baseline). | All participants were analyzed. | Posted | Number | Percentage of BCCs | 4 weeks, 6 weeks, 9 weeks | Tumors (BCCs) | Participants |
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| Secondary | Change From Baseline in Tumor Measurements (Part I) | Measurement of the tumor size, volume and color by standardized digital photography, using dermatoscopic, macroscopic and 3D images of the BCCs was done by participant where if a participant had more than one tumor, for each of these tumors, the change from baseline was calculated (% change). From these values, the mean was calculated to get only one result per participant. Then for all the participants (n=8 both for LDE and vehicle), the mean was calculated. Photographic analysis was conducted by QuantifiCare. The volume of a lesion was measured with a special device, the "3D LIFEVIZ Micro system", which uses a lens splitter to produce two images of the skin surface, captured at the same time, with viewing angle differences close to human vision. A stereovision algorithm is then applied to reconstruct and quantitatively analyze the skin surface in 3D. A negative change from baseline indicates improvement. | All part I participants were included in the analysis. | Posted | Mean | Standard Deviation | Percent change in tumor measurement | 4 weeks |
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| Secondary | Change From Baseline in Tumor Measurements (Part II) | Measurement of the tumor size, volume and color by standardized digital photography, using dermatoscopic, macroscopic and 3D images of the BCCs was done by participant where if a participant had more than one tumor, for each of these tumors, the change from baseline was calculated (% change). From these values, the mean was calculated to get only one result per participant. Then for all the participants (n=8 both for LDE and vehicle), the mean was calculated.. Photographic analysis was conducted by QuantifiCare. The volume of a lesion was measured with a special device, the "3D LIFEVIZ Micro system", which uses a lens splitter to produce two images of the skin surface, captured at the same time, with viewing angle differences close to human vision. A stereovision algorithm is then applied to reconstruct and quantitatively analyze the skin surface in 3D. A negative change from baseline indicates improvement. | Part II participants with evaluable data (n=3,6) were included in the analysis. | Posted | Mean | Standard Deviation | percent change in tumor measurement | 4 weeks, 6 weeks, 9 weeks |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Tumor Measurements (by Tumor) (Part I) | Measurement of the tumor size, volume and color by standardized digital photography, using dermatoscopic, macroscopic and 3D images of the BCCs. Photographic analysis was conducted by QuantifiCare. The volume of a lesion was measured with a special device, the "3D LIFEVIZ Micro system", which uses a lens splitter to produce two images of the skin surface, captured at the same time, with viewing angle differences close to human vision. A stereovision algorithm is then applied to reconstruct and quantitatively analyze the skin surface in 3D. A negative change from baseline indicates improvement. | All part I participants were included in this analysis. | Posted | Mean | Standard Deviation | Percent change in tumor measurement | 4 weeks | tumors (BCCs) | Participants |
| ||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Tumor Measurements (by Tumor) (Part II) | Measurement of the tumor size, volume and color by standardized digital photography, using dermatoscopic, macroscopic and 3D images of the BCCs. Photographic analysis was conducted by QuantifiCare. The volume of a lesion was measured with a special device, the "3D LIFEVIZ Micro system", which uses a lens splitter to produce two images of the skin surface, captured at the same time, with viewing angle differences close to human vision. A stereovision algorithm is then applied to reconstruct and quantitatively analyze the skin surface in 3D. A negative change from baseline indicates improvement. | Part II participants with evaluable data (n=3,6) were included in the analysis. | Posted | Mean | Standard Deviation | Percent change in tumor measurement | 4 weeks, 6 weeks, 9 weeks | Tumors (BCCs) | Participants |
| ||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With at Least Partial Clinical Clearance (Part I) | Clinical response parameters were defined as (i) complete response (i.e., there is no longer any visible evidence of a lesion consistent with BCC at this site), (ii) partial response (i.e., although a BCC still remains at this site, it has demonstrated a visible decrease in size compared with baseline), and (iii) no response / worsening (i.e., the BCC has not demonstrated any visible decrease in size compared with baseline). | All part I participants were included in the analysis. | Posted | Number | Number of participants | day 8, day 15, day 22, day 29 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Part I Participants | Participants were exposed to both topically applied 0.75% LDE225 cream and LDE225 vehicle cream twice daily for 28 days where each treatment was randomized to two different test areas on each participant. | 0 | 8 | 7 | 8 | ||
| EG001 | 0.25% LDE225 [Part II] | Participants were exposed to topically applied 0.25% LDE225 cream twice daily for 6 weeks. | 0 | 3 | 2 | 3 | ||
| EG002 | 0.75% LDE225 [Part II] | Participants were exposed to topically applied 0.75% LDE225 cream twice daily where some basal cell carcinomas (BCCs) were treated for 6 weeks and some BCCs were treated for 9 weeks. | 1 | 7 | 5 | 7 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| HEPATIC ENZYME INCREASED | Investigations | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| EXTERNAL EAR INFLAMMATION | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
| |
| CONJUNCTIVITIS | Eye disorders | MedDRA | Systematic Assessment |
| |
| FATIGUE | General disorders | MedDRA | Systematic Assessment |
| |
| INFECTION | Infections and infestations | MedDRA | Systematic Assessment |
| |
| NASOPHARYNGITIS | Infections and infestations | MedDRA | Systematic Assessment |
| |
| ARTHROPOD STING | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| INJURY CORNEAL | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| LIMB INJURY | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| BLOOD CHOLESTEROL INCREASED | Investigations | MedDRA | Systematic Assessment |
| |
| BLOOD GLUCOSE INCREASED | Investigations | MedDRA | Systematic Assessment |
| |
| BLOOD TRIGLYCERIDES INCREASED | Investigations | MedDRA | Systematic Assessment |
| |
| GAMMA-GLUTAMYLTRANSFERASE INCREASED | Investigations | MedDRA | Systematic Assessment |
| |
| GLUCOSE URINE PRESENT | Investigations | MedDRA | Systematic Assessment |
| |
| HAEMATOCRIT DECREASED | Investigations | MedDRA | Systematic Assessment |
| |
| HAEMOGLOBIN DECREASED | Investigations | MedDRA | Systematic Assessment |
| |
| WHITE BLOOD CELLS URINE POSITIVE | Investigations | MedDRA | Systematic Assessment |
| |
| IRON DEFICIENCY | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
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| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| ASTHMA | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| SKIN FISSURES | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| SKIN IRRITATION | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| URTICARIA | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
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The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis | 862-778-8300 |
| ID | Term |
|---|---|
| D002280 | Carcinoma, Basal Cell |
| D001478 | Basal Cell Nevus Syndrome |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D018295 | Neoplasms, Basal Cell |
| D009807 | Odontogenic Cysts |
| D007570 | Jaw Cysts |
| D001845 | Bone Cysts |
| D003560 | Cysts |
| D009386 | Neoplastic Syndromes, Hereditary |
| D001848 | Bone Diseases, Developmental |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D007571 | Jaw Diseases |
| D009057 | Stomatognathic Diseases |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
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| Male |
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| Tumors (BCCs) |
|
| Week 4, complete |
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| Week 6, at least partial |
|
| Week 6, complete |
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| Week 9, at least partial (LDE 0.75%, n=10) |
|
| Week 9, complete (LDE 0.75%, n=10) |
|
Participants were exposed to both topically applied 0.75% LDE225 cream and LDE225 vehicle cream twice daily for 28 days where each treatment was randomized to two different test areas on each participant.
Vehicle: Placebo cream
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| Tumors (BCCs) |
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