Long-term Trial of Topical Sirolimus to Angiofibroma in Patient With Tuberous Sclerosis Complex

Plaque Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02634931
• Other study ID #: NPC-12G-2
• Status: Completed
• Phase: Phase 3
• Start date: December 2015
• Est. completion date: October 2018

Study information

• Verified date: December 2015
• Source: Nobelpharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: October 2018
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years and older

Eligibility

Inclusion Criteria:

1. Male or female patients 3 years old or greater at the time of informed consent

2. Patients who are diagnosed as definite diagnosis according to diagnostic criteria for tuberous sclerosis complex (International Tuberous Sclerosis Complex Consensus Conference 2012)

3. 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

4. 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)

5. Patient who are considered to be an appropriate patient to participate in the trial by investigator

6. 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:

1. Patients who have offered to withdraw from Phase III trial (NPC-12G-1) and have been discontinued

2. 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)

3. 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

4. Patients with a history of hypersensitivity to alcohol or allergy to sirolimus

5. 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''

6. 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.

7. Female patients who may be pregnancy or are lactating

8. Patients who cannot agree to take appropriate measures of contraception until completion of the trial or follow-up period after discontinuation from informed consent

9. 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

10. Others, patients who are considered by the investigator as unsuitable for participation in the trial

Related Conditions & MeSH terms

• Angiofibroma
• Hypomelanotic Macule
• Plaque
• Sclerosis
• Tuberous Sclerosis

Intervention

Drug:
• NPC-12G gel
NPC-12G gel is administered topically twice a day for 52 weeks or longer

Locations

Country	Name	City	State
Japan	Graduate School of Medicine, Osaka University	Suita, Osaka

Sponsors (1)

Lead Sponsor	Collaborator
Nobelpharma

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	52 weeks and longer
Secondary	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	52 weeks and longer
Secondary	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	52 weeks and longer
Secondary	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	52 weeks and longer
Secondary	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	52 weeks and longer
Secondary	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	52 weeks and longer
Secondary	Laboratory tests, vital signs	Completion of week 26 and 52 are cut-off points for interim-analyses	Baseline and every 3 months for laboratory tests, every scheduled visit for vital sign]
Secondary	Blood level of sirolimus	Whole blood level of sirolimus are measured any day time at baseline and every 3 months visit	Baseline and every 3 months only for the first trial phase
Secondary	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.	Week 4, 8, 12, 26, 39 and 52
Secondary	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.	Week 4, 8, 12, 26, 39 and 52
Secondary	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.	Week 4, 8, 12, 26, 39 and 52
Secondary	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.	Week 4, 8, 12, 26, 39 and 52
Secondary	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.	Week 4, 8, 12, 26, 39 and 52
Secondary	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.	Week 4, 8, 12, 26, 39 and 52
Secondary	Degree of patient's satisfaction	Patient's satisfaction is assessed by patient. Completion of week 26 is a cut-off point for interim-analysis.	Week 12, 26, 39 and 52