Back to resultsLong-term Trial of Topical Sirolimus to Angiofibroma in Patient With Tuberous Sclerosis Complex
Primary Purpose
Tuberous Sclerosis, Angiofibroma, Hypomelanotic Macule
Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
NPC-12G gel
Sponsored by
About this trial
This is an interventional treatment trial for Tuberous Sclerosis focused on measuring Sirolimus, Skin lesions, TSC, Tuberous Sclerosis Complex, NPC-12G, Angiofibroma, Hypomelanotic Macule, Plaque
Eligibility Criteria
Inclusion Criteria:
- Male or female patients 3 years old or greater at the time of informed consent
- Patients who are diagnosed as definite diagnosis according to diagnostic criteria for tuberous sclerosis complex (International Tuberous Sclerosis Complex Consensus Conference 2012)
- Patients with skin lesions such as angiofibroma, white macules or plaque upper neck associated with tuberous sclerosis complex at the screening visit or the baseline visit
- Patients or his/her guardian who agree to use the test drug (NPC-12G gel) or who want to participate in the trial again following participation in Phase III trial (NPC-12G-1)
- Patient who are considered to be an appropriate patient to participate in the trial by investigator
- Patients or his/her guardian who give a written informed consent in understanding and willingness after having received enough explanation of the test drug and the current trial plan
Exclusion Criteria:
- Patients who have offered to withdraw from Phase III trial (NPC-12G-1) and have been discontinued
- Patients who have not applied the test drug topically more than 25% of whole applications without appropriate reason for Phase III trial (NPC-12G-1)
- Patients with clinical findings such as erosion, ulcer and eruption on or around the lesion of angiofibroma, which may affect assessment of safety or efficacy
- Patients with a history of hypersensitivity to alcohol or allergy to sirolimus
- Patients who have complications such as malignant tumor, infection, serious heart disease, hepatic function disorder, renal function disorder or blood disorders which severity are considered by investigator as grade 2 or more severe with reference to ''Concerning classification criteria for seriousness of adverse drug reactions of medical agents''
- Patients who have complications such as diseases unsuitable for the trial participation, for examples, uncontrolled diabetes (fasting blood glucose level >140 mg/dL or postprandial blood glucose level > 200 mg/dL), dyslipidemia (cholesterol level > 300 mg/dL or > 7.75 mmol/L, triglycerides level > 300 mg/dL or > 3.42 mmol/L), etc.
- Female patients who may be pregnancy or are lactating
- Patients who cannot agree to take appropriate measures of contraception until completion of the trial or follow-up period after discontinuation from informed consent
- Patients who have participated in other clinical trial other than Phase III trial (NPC-12G-1) and have taken a trial drug within 6 months before informed consent
- Others, patients who are considered by the investigator as unsuitable for participation in the trial
Sites / Locations
- Graduate School of Medicine, Osaka University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
NPC-12G gel
Arm Description
NPC-12G gel is containing 0.2% Sirolimus
Outcomes
Primary Outcome Measures
The discontinuation rate due to adverse events
The first discontinuation in each patient due to adverse events is assessed.Completion of week 26 and 52 are cut-off points for interim-analyses by Kaplan-Meier method
Secondary Outcome Measures
Adverse events and adverse events related to the test drug
The number of discontinuation/ resume due to adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Adverse events related to the test drug leading to the discontinuation permanently
The incidence of adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Serious adverse events and serious adverse events related to the test drug
The incidence of serious adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Adverse events and adverse events related to the test drug leading to modification of dosage and administration
The incidence of adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Significant adverse events and significant adverse events related to the test drug
The incidence of significant adverse events such as local irritation are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Laboratory tests, vital signs
Completion of week 26 and 52 are cut-off points for interim-analyses
Blood level of sirolimus
Whole blood level of sirolimus are measured any day time at baseline and every 3 months visit
Improvements in angiofibroma
Improvements comparing with baseline is assessed using photograph by the investigator and the central photo-judgement committee. Completion of week 26 is a cut-off point for interim-analysis.
Improvements in sizes of angiofibroma
Improvements comparing with baseline is assessed using photograph by the investigator and the central photo-judgement committee. Completion of week 26 is a cut-off point for interim-analysis.
Improvements in redness of angiofibroma
Improvements comparing with baseline is assessed using photograph by the investigator and the central photo-judgement committee. Completion of week 26 is a cut-off point for interim-analysis.
Improvements in white macule and plaque upper neck
Improvements comparing with baseline is assessed using photograph by the investigator and the central photo-judgement committee. Completion of week 26 is a cut-off point for interim-analysis.
The rate of patients evaluated ''improvement'' or more (improvement rate) in above the efficacy measures.
Completion of week 26 is a cut-off point for interim-analysis.
Change in total score of DLQI and CDLQI from baseline
DLQI for subjects 16 years old and greater, or CDLQI for children of less than 16 years old is assessed by patients. Completion of week 26 is a cut-off point for interim-analysis.
Degree of patient's satisfaction
Patient's satisfaction is assessed by patient. Completion of week 26 is a cut-off point for interim-analysis.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02634931
Brief Title
Long-term Trial of Topical Sirolimus to Angiofibroma in Patient With Tuberous Sclerosis Complex
Official Title
A Long-term, Single-arm, Open-label Trial of NPC-12G (Topical Formulation of Sirolimus) to Angiofibroma and Other Skin Lesions in Patients With Tuberous Sclerosis Complex
Study Type
Interventional
2. Study Status
Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
December 2015 (undefined)
Primary Completion Date
October 2018 (Actual)
Study Completion Date
October 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nobelpharma
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this trial is to evaluate the safety and efficacy of long-term treatment with NPC-12G gel (0.2% sirolimus gel) to angiofibroma and other skin lesions in patients with tuberous sclerosis complex in the open-label trial.
Detailed Description
Tuberous Sclerosis Complex (TSC) is an autosomal dominant hereditary disease that causes benign tumors on the almost whole body (including skin, brain, kidney, lung and heart), behavior disorder as autism, mental retardation and neurologic symptom as epilepsy. Angiofibroma is a TSC-specific facial skin lesion, and hamartoma caused by increase of the component of skin connective tissues and blood vessels. Other skin lesions due to TSC are white macule (hypomelanotic macule), plaque, shagreen patch and ungual fibromas. Current therapeutic methods for angiofibroma are laser and surgical treatments, but there are problems as many relapses, deficiency of evidence, change of pigment, scar and risk of infection.
This is a multicenter and open-label trial. The trial consists of two phase. In the first trial phase for 52 weeks, the efficacy as well as the safety is evaluated. For the second trial phase the trial will be continued until the date of approval of NDA for NPC-12G. The safety is evaluated during the second trial phase, but not the efficacy. Patients who meet all entry criteria for the trial apply 0.2% NPC-12G gel twice a day. Patients will visit at 4 to 5-week intervals for the first 6 months of the first trial phase, and then 3 months intervals thereafter.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberous Sclerosis, Angiofibroma, Hypomelanotic Macule, Plaque
Keywords
Sirolimus, Skin lesions, TSC, Tuberous Sclerosis Complex, NPC-12G, Angiofibroma, Hypomelanotic Macule, Plaque
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
94 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NPC-12G gel
Arm Type
Experimental
Arm Description
NPC-12G gel is containing 0.2% Sirolimus
Intervention Type
Drug
Intervention Name(s)
NPC-12G gel
Intervention Description
NPC-12G gel is administered topically twice a day for 52 weeks or longer
Primary Outcome Measure Information:
Title
The discontinuation rate due to adverse events
Description
The first discontinuation in each patient due to adverse events is assessed.Completion of week 26 and 52 are cut-off points for interim-analyses by Kaplan-Meier method
Time Frame
52 weeks and longer
Secondary Outcome Measure Information:
Title
Adverse events and adverse events related to the test drug
Description
The number of discontinuation/ resume due to adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Time Frame
52 weeks and longer
Title
Adverse events related to the test drug leading to the discontinuation permanently
Description
The incidence of adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Time Frame
52 weeks and longer
Title
Serious adverse events and serious adverse events related to the test drug
Description
The incidence of serious adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Time Frame
52 weeks and longer
Title
Adverse events and adverse events related to the test drug leading to modification of dosage and administration
Description
The incidence of adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Time Frame
52 weeks and longer
Title
Significant adverse events and significant adverse events related to the test drug
Description
The incidence of significant adverse events such as local irritation are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
Time Frame
52 weeks and longer
Title
Laboratory tests, vital signs
Description
Completion of week 26 and 52 are cut-off points for interim-analyses
Time Frame
Baseline and every 3 months for laboratory tests, every scheduled visit for vital sign]
Title
Blood level of sirolimus
Description
Whole blood level of sirolimus are measured any day time at baseline and every 3 months visit
Time Frame
Baseline and every 3 months only for the first trial phase
Title
Improvements in angiofibroma
Description
Improvements comparing with baseline is assessed using photograph by the investigator and the central photo-judgement committee. Completion of week 26 is a cut-off point for interim-analysis.
Time Frame
Week 4, 8, 12, 26, 39 and 52
Title
Improvements in sizes of angiofibroma
Description
Improvements comparing with baseline is assessed using photograph by the investigator and the central photo-judgement committee. Completion of week 26 is a cut-off point for interim-analysis.
Time Frame
Week 4, 8, 12, 26, 39 and 52
Title
Improvements in redness of angiofibroma
Description
Improvements comparing with baseline is assessed using photograph by the investigator and the central photo-judgement committee. Completion of week 26 is a cut-off point for interim-analysis.
Time Frame
Week 4, 8, 12, 26, 39 and 52
Title
Improvements in white macule and plaque upper neck
Description
Improvements comparing with baseline is assessed using photograph by the investigator and the central photo-judgement committee. Completion of week 26 is a cut-off point for interim-analysis.
Time Frame
Week 4, 8, 12, 26, 39 and 52
Title
The rate of patients evaluated ''improvement'' or more (improvement rate) in above the efficacy measures.
Description
Completion of week 26 is a cut-off point for interim-analysis.
Time Frame
Week 4, 8, 12, 26, 39 and 52
Title
Change in total score of DLQI and CDLQI from baseline
Description
DLQI for subjects 16 years old and greater, or CDLQI for children of less than 16 years old is assessed by patients. Completion of week 26 is a cut-off point for interim-analysis.
Time Frame
Week 4, 8, 12, 26, 39 and 52
Title
Degree of patient's satisfaction
Description
Patient's satisfaction is assessed by patient. Completion of week 26 is a cut-off point for interim-analysis.
Time Frame
Week 12, 26, 39 and 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients 3 years old or greater at the time of informed consent
Patients who are diagnosed as definite diagnosis according to diagnostic criteria for tuberous sclerosis complex (International Tuberous Sclerosis Complex Consensus Conference 2012)
Patients with skin lesions such as angiofibroma, white macules or plaque upper neck associated with tuberous sclerosis complex at the screening visit or the baseline visit
Patients or his/her guardian who agree to use the test drug (NPC-12G gel) or who want to participate in the trial again following participation in Phase III trial (NPC-12G-1)
Patient who are considered to be an appropriate patient to participate in the trial by investigator
Patients or his/her guardian who give a written informed consent in understanding and willingness after having received enough explanation of the test drug and the current trial plan
Exclusion Criteria:
Patients who have offered to withdraw from Phase III trial (NPC-12G-1) and have been discontinued
Patients who have not applied the test drug topically more than 25% of whole applications without appropriate reason for Phase III trial (NPC-12G-1)
Patients with clinical findings such as erosion, ulcer and eruption on or around the lesion of angiofibroma, which may affect assessment of safety or efficacy
Patients with a history of hypersensitivity to alcohol or allergy to sirolimus
Patients who have complications such as malignant tumor, infection, serious heart disease, hepatic function disorder, renal function disorder or blood disorders which severity are considered by investigator as grade 2 or more severe with reference to ''Concerning classification criteria for seriousness of adverse drug reactions of medical agents''
Patients who have complications such as diseases unsuitable for the trial participation, for examples, uncontrolled diabetes (fasting blood glucose level >140 mg/dL or postprandial blood glucose level > 200 mg/dL), dyslipidemia (cholesterol level > 300 mg/dL or > 7.75 mmol/L, triglycerides level > 300 mg/dL or > 3.42 mmol/L), etc.
Female patients who may be pregnancy or are lactating
Patients who cannot agree to take appropriate measures of contraception until completion of the trial or follow-up period after discontinuation from informed consent
Patients who have participated in other clinical trial other than Phase III trial (NPC-12G-1) and have taken a trial drug within 6 months before informed consent
Others, patients who are considered by the investigator as unsuitable for participation in the trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mari Wataya-Kaneda,, MD, PhD
Organizational Affiliation
Department of Dermatology, Graduate School of Medicine, Osaka University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Graduate School of Medicine, Osaka University
City
Suita, Osaka
ZIP/Postal Code
565-0871
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
32385845
Citation
Wataya-Kaneda M, Nagai H, Ohno Y, Yokozeki H, Fujita Y, Niizeki H, Yoshida K, Ogai M, Yoshida Y, Asahina A, Fukai K, Tateishi C, Hamada I, Takahata T, Shimizu K, Shimasaki S, Murota H. Safety and Efficacy of the Sirolimus Gel for TSC Patients With Facial Skin Lesions in a Long-Term, Open-Label, Extension, Uncontrolled Clinical Trial. Dermatol Ther (Heidelb). 2020 Aug;10(4):635-650. doi: 10.1007/s13555-020-00387-7. Epub 2020 May 8.
Results Reference
derived
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Long-term Trial of Topical Sirolimus to Angiofibroma in Patient With Tuberous Sclerosis Complex
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