Trial Outcomes & Findings for Efficacy, Safety and Pharmacokinetics of Oral LDE225 in Treatment of Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS) (NCT NCT01350115)
NCT ID: NCT01350115
Last Updated: 2015-10-19
Results Overview
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.
COMPLETED
PHASE2
10 participants
Day 113
2015-10-19
Participant Flow
Participants were assigned to one of the following 2 treatment arms in a ratio of 6:1,LDE225 400 mg QD and Placebo QD.
Participant milestones
| Measure |
LDE225
Participants received 400 mg once daily.
|
Placebo
Participants received matching placebo.
|
|---|---|---|
|
Core Study (All Patients)
STARTED
|
8
|
2
|
|
Core Study (All Patients)
Safety Anlysis Set
|
8
|
2
|
|
Core Study (All Patients)
Pharmacodynamic Set
|
7
|
2
|
|
Core Study (All Patients)
COMPLETED
|
8
|
2
|
|
Core Study (All Patients)
NOT COMPLETED
|
0
|
0
|
|
Long Term Follow-Up (All Patients)
STARTED
|
8
|
2
|
|
Long Term Follow-Up (All Patients)
COMPLETED
|
7
|
0
|
|
Long Term Follow-Up (All Patients)
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
LDE225
Participants received 400 mg once daily.
|
Placebo
Participants received matching placebo.
|
|---|---|---|
|
Long Term Follow-Up (All Patients)
Lost to Follow-up
|
0
|
1
|
|
Long Term Follow-Up (All Patients)
Adverse Event
|
0
|
1
|
|
Long Term Follow-Up (All Patients)
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Efficacy, Safety and Pharmacokinetics of Oral LDE225 in Treatment of Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS)
Baseline characteristics by cohort
| Measure |
LDE225
n=8 Participants
Participants received 400 mg once daily.
|
Placebo
n=2 Participants
Participants received matching placebo.
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.5 Years
STANDARD_DEVIATION 9.90 • n=5 Participants
|
66 Years
STANDARD_DEVIATION 2.00 • n=7 Participants
|
53.6 Years
STANDARD_DEVIATION 10.95 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 113Population: All participants, who had evaluable (or complete) pharmacodynamic (PD) or biomarker parameter data and were without protocol deviations with significant impact on the PD data, were included in the PD analysis set.
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.
Outcome measures
| Measure |
LDE225
n=7 Participants
Participants received 400 mg once daily.
|
Placebo
n=2 Participants
Participants received matching placebo.
|
|---|---|---|
|
Clinical Clearance Assessment of Main Target Basal Cell Carcinomas (BCCs)
Complete Clearance (100% Improvement)
|
3 Participants
|
0 Participants
|
|
Clinical Clearance Assessment of Main Target Basal Cell Carcinomas (BCCs)
Marked Clearance (76-99% Improvement)
|
3 Participants
|
0 Participants
|
|
Clinical Clearance Assessment of Main Target Basal Cell Carcinomas (BCCs)
Moderate Clearance (26-75% improvement)
|
1 Participants
|
0 Participants
|
|
Clinical Clearance Assessment of Main Target Basal Cell Carcinomas (BCCs)
Slight Clearance (1-25%)
|
0 Participants
|
1 Participants
|
|
Clinical Clearance Assessment of Main Target Basal Cell Carcinomas (BCCs)
Worsening
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: day 113Population: All participants, who had evaluable (or complete) pharmacodynamic (PD) or biomarker parameter data and were without protocol deviations with significant impact on the PD data, were included in the PD analysis set.
The main (and secondary, if appropriate) target BCC tumor area(s) was/were excised surgically and sent to a central laboratory for histological examination.
Outcome measures
| Measure |
LDE225
n=7 Participants
Participants received 400 mg once daily.
|
Placebo
n=2 Participants
Participants received matching placebo.
|
|---|---|---|
|
Histological Clearance Assessment of Main Target BCCs
Histological clearance
|
57 Percentage of participants
|
0 Percentage of participants
|
|
Histological Clearance Assessment of Main Target BCCs
Complete clinical (up to day 85) & histological
|
14 Percentage of participants
|
0 Percentage of participants
|
|
Histological Clearance Assessment of Main Target BCCs
Complete clinical (up to day 113) & histological
|
29 Percentage of participants
|
0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, day 85, and day 113Population: All participants, who had evaluable (or complete) pharmacodynamic (PD) or biomarker parameter data and were without protocol deviations with significant impact on the PD data, were included in the PD analysis set.
BCC tumor counts were performed separately for five body regions: head and neck, trunk back, trunk front (including axillae and groin), upper extremities and lower extremities (including buttocks). During the counting, the BCC tumors, were categorized upon inspection by their longest diameter measurement (\<10 mm, 10-19 mm, 20-29 mm, and \>+30mm), and also by the type of BCC (superficial, nodular, other). The counts for all of the BCC type and size categories were determined (or estimated if many small lesions) for each body region. The body region counts were summated to provide the overall BCC tumor count.
Outcome measures
| Measure |
LDE225
n=7 Participants
Participants received 400 mg once daily.
|
Placebo
n=2 Participants
Participants received matching placebo.
|
|---|---|---|
|
Measure: Disease Burden by BCC Tumor Counts
Baseline
|
566 Number of BCC tumors
|
510 Number of BCC tumors
|
|
Measure: Disease Burden by BCC Tumor Counts
Day 85
|
341 Number of BCC tumors
|
571 Number of BCC tumors
|
|
Measure: Disease Burden by BCC Tumor Counts
Day 113
|
309 Number of BCC tumors
|
619 Number of BCC tumors
|
Adverse Events
LDE225 - Core
Placebo - Core
LDE225 - Long Term Follow-up
Placebo - Long Term Follow-up
Serious adverse events
| Measure |
LDE225 - Core
n=8 participants at risk
Participants received 400 mg once daily.
|
Placebo - Core
n=2 participants at risk
Participants received matching placebo.
|
LDE225 - Long Term Follow-up
n=8 participants at risk
|
Placebo - Long Term Follow-up
n=2 participants at risk
|
|---|---|---|---|---|
|
Infections and infestations
Cellulitis
|
0.00%
0/8
|
0.00%
0/2
|
12.5%
1/8
|
0.00%
0/2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/8
|
50.0%
1/2
|
0.00%
0/8
|
0.00%
0/2
|
Other adverse events
| Measure |
LDE225 - Core
n=8 participants at risk
Participants received 400 mg once daily.
|
Placebo - Core
n=2 participants at risk
Participants received matching placebo.
|
LDE225 - Long Term Follow-up
n=8 participants at risk
|
Placebo - Long Term Follow-up
n=2 participants at risk
|
|---|---|---|---|---|
|
Cardiac disorders
Cardiovascular disorder
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Ear and labyrinth disorders
Vertigo positional
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Eye disorders
Eyelid irritation
|
0.00%
0/8
|
50.0%
1/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Eye disorders
Vision blurred
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/8
|
50.0%
1/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Gastrointestinal disorders
Food poisoning
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Gastrointestinal disorders
Gingival pain
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Gastrointestinal disorders
Nausea
|
25.0%
2/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Gastrointestinal disorders
Vomiting
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
General disorders
Fatigue
|
25.0%
2/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Infections and infestations
Folliculitis
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Infections and infestations
Laryngitis
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Infections and infestations
Nasopharyngitis
|
25.0%
2/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Infections and infestations
Postoperative wound infection
|
0.00%
0/8
|
50.0%
1/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Infections and infestations
Sinusitis
|
0.00%
0/8
|
0.00%
0/2
|
12.5%
1/8
|
0.00%
0/2
|
|
Infections and infestations
Wound infection
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Injury, poisoning and procedural complications
Electric shock
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Investigations
Alanine aminotransferase increased
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Investigations
Aspartate aminotransferase increased
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Investigations
Blood creatine phosphokinase increased
|
25.0%
2/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Investigations
Gamma-glutamyltransferase increased
|
12.5%
1/8
|
0.00%
0/2
|
12.5%
1/8
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
37.5%
3/8
|
50.0%
1/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/8
|
50.0%
1/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Nervous system disorders
Dizziness
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Nervous system disorders
Dysgeusia
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Nervous system disorders
Headache
|
25.0%
2/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
25.0%
2/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
|
Skin and subcutaneous tissue disorders
Neurodermatitis
|
0.00%
0/8
|
0.00%
0/2
|
12.5%
1/8
|
0.00%
0/2
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
12.5%
1/8
|
0.00%
0/2
|
0.00%
0/8
|
0.00%
0/2
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER