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Tuberous Sclerosis

Angiofibroma

Hamartoma

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Tuberous Sclerosis Complex

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All Drugs and Chemicals

Sirolimus

Placebo gel is matched ingredient with NPC-12G gel

NPC-12G gel is administered topically twice a day for 12 weeks

NPC-12G gel

NPC-12G gel placebo is administered topically twice a day for 12 weeks

Placebo gel

Mari Wataya-Kaneda, MD, PhD

The purpose of this trial is to evaluate the efficacy and safety of NPC-12G gel (topical formulation of sirolimus) versus placebo gel to facial angiofibroma and other skin lesions in patients with tuberous sclerosis complex (TSC)

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 TSC-specific facial skin lesions, 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 or surgical treatments, but there are problems as many relapses, deficiency of evidence, change of pigment, scar and risk of infection.

This will be a multicenter, double-blind, randomized, placebo-controlled parallel group trial. The trial has three phases; the screening phase, double-blinded treatment phase, and post-treatment phase. The screening phase comprises a screening visit where subject's initial eligibility will be evaluated. During double-blinded treatment phase, patients who meet all entry criteria for the trial will be randomized into two groups, and they will apply 0.2% NPC-12G gel or placebo gel topically twice a day for 12 weeks.

Phase III Trial of Topical Formulation of Sirolimus to Skin Lesions in Patients With Tuberous Sclerosis Complex (TSC)

A Double-blind, Randomized, Placebo-controlled Phase III Trial to Investigate the Efficacy and Safety of NPC-12G Gel (Topical Formulation of Sirolimus) to Angiofibroma and Other Skin Lesions in Patients With Tuberous Sclerosis Complex

Improvements comparing with baseline is assessed using photograph by the central photo-judgement committee

Improvements comparing with baseline is assessed by the investigator

Improvement comparing with baseline is assessed by the central photo-judgement committee and the investigator

DLQI for subjects 16 years old and greater, or CDLQI for children of less than 16 years old is assessed by patients

Serious adverse events during the study period

Laboratory findings during the study period

Blood concentration of Sirolimus is assessed by drug monitoring

Nobelpharma

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

Mari Wataya-Kaneda,, MD, PhD

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.

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.

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

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

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

The number of discontinuation/ resume due to adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses

The incidence of adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses

The incidence of serious adverse events are evaluated. Completion of week 26 and 52 are cut-off points for interim-analyses

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

Completion of week 26 and 52 are cut-off points for interim-analyses

Whole blood level of sirolimus are measured any day time at baseline and every 3 months visit

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.

Completion of week 26 is a cut-off point for interim-analysis.

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.

Patient's satisfaction is assessed by patient. Completion of week 26 is a cut-off point for interim-analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase III Trial of Topical Formulation of Sirolimus to Skin Lesions in Patients With Tuberous Sclerosis Complex (TSC)	NCT02635789	Tuberous Sclero... Angiofibroma Hypomelanotic M... Plaque	NPC-12G gel Placebo gel	3 Years -	Nobelpharma
Long-term Trial of Topical Sirolimus to Angiofibroma in Patient With Tuberous Sclerosis Complex	NCT02634931	Tuberous Sclero... Angiofibroma Hypomelanotic M... Plaque	NPC-12G gel	3 Years -	Nobelpharma
Phase III Trial of Topical Formulation of Sirolimus to Skin Lesions in Patients With Tuberous Sclerosis Complex (TSC)	NCT02635789	Tuberous Sclero... Angiofibroma Hypomelanotic M... Plaque	NPC-12G gel Placebo gel	3 Years -	Nobelpharma
Phase III Trial of Topical Formulation of Sirolimus to Skin Lesions in Patients With Tuberous Sclerosis Complex (TSC)	NCT02635789	Tuberous Sclero... Angiofibroma Hypomelanotic M... Plaque	NPC-12G gel Placebo gel	3 Years -	Nobelpharma

Spots Global Cancer Trial Database for hypomelanotic macule