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

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

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

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 Summary:

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.


Sponsor: Nobelpharma

Current Primary Outcome: The discontinuation rate due to adverse events [ Time Frame: 52 weeks and longer ]

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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Adverse events and adverse events related to the test drug [ Time Frame: 52 weeks and longer ]
    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 [ Time Frame: 52 weeks and longer ]
    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 [ Time Frame: 52 weeks and longer ]
    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 [ Time Frame: 52 weeks and longer ]
    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 [ Time Frame: 52 weeks and longer ]
    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 [ Time Frame: Baseline and every 3 months for laboratory tests, every scheduled visit for vital sign] ]
    Completion of week 26 and 52 are cut-off points for interim-analyses
  • Blood level of sirolimus [ Time Frame: Baseline and every 3 months only for the first trial phase ]
    Whole blood level of sirolimus are measured any day time at baseline and every 3 months visit
  • Improvements in angiofibroma [ Time Frame: Week 4, 8, 12, 26, 39 and 52 ]
    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 [ Time Frame: Week 4, 8, 12, 26, 39 and 52 ]
    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 [ Time Frame: Week 4, 8, 12, 26, 39 and 52 ]
    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 [ Time Frame: Week 4, 8, 12, 26, 39 and 52 ]
    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. [ Time Frame: Week 4, 8, 12, 26, 39 and 52 ]
    Completion of week 26 is a cut-off point for interim-analysis.
  • Change in total score of DLQI and CDLQI from baseline [ Time Frame: Week 4, 8, 12, 26, 39 and 52 ]
    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 [ Time Frame: Week 12, 26, 39 and 52 ]
    Patient's satisfaction is assessed by patient. Completion of week 26 is a cut-off point for interim-analysis.


Original Secondary Outcome:

  • Adverse events and adverse events related to the test drug [ Time Frame: 52 weeks and longer ]
    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 [ Time Frame: 52 weeks and longer ]
    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 [ Time Frame: 52 weeks and longer ]
    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 [ Time Frame: 52 weeks and longer ]
    The incidence of adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses
  • Significant adverse events and adverse events related to the test drug [ Time Frame: 52 weeks and longer ]
    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 [ Time Frame: Baseline and every 3 months for laboratory tests, every scheduled visit for vital sign] ]
    Completion of week 26 and 52 are cut-off points for interim-analyses
  • Blood level of sirolimus [ Time Frame: Baseline and every 3 months only for the first trial phase ]
    Whole blood level of sirolimus are measured any day time at baseline and every 3 months visit
  • Improvements in angiofibroma [ Time Frame: Week 4, 8, 12, 26, 39 and 52 ]
    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 [ Time Frame: Week 4, 8, 12, 26, 39 and 52 ]
    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 [ Time Frame: Week 4, 8, 12, 26, 39 and 52 ]
    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 [ Time Frame: Week 4, 8, 12, 26, 39 and 52 ]
    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 (improvement rate) evaluated ''improvement'' or more in above item 9 to 12. [ Time Frame: Week 4, 8, 12, 26, 39 and 52 ]
    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.
  • Change in total score of DLQI and CDLQI from baseline [ Time Frame: Week 4, 8, 12, 26, 39 and 52 ]
    DLQI or CDLQI for children less 16 years old is assessed by patients. Completion of week 26 is a cut-off point for interim-analysis.
  • Degree of patient's satisfaction [ Time Frame: Week 12, 26, 39 and 52 ]
    Patient's satisfaction is assessed by patient. Completion of week 26 is a cut-off point for interim-analysis.


Information By: Nobelpharma

Dates:
Date Received: December 16, 2015
Date Started: December 2015
Date Completion: February 2018
Last Updated: December 21, 2015
Last Verified: December 2015