Topical Rapamycin Therapy to Alleviate Cutaneous Manifestations of Tuberous Sclerosis Complex (TSC) and Neurofibromatosis I (NF1)

Study Overview
=================
Brief Summary
-----------------
This study is a prospective, randomized, double-blind, placebo-controlled evaluation of the safety of a topically applied formulation of rapamycin to cutaneous fibromatous lesions in subjects with Tuberous Sclerosis Complex (TSC) and Neurofibromatosis I (NF1). Subjects will apply either a Polyvinylidene fluoride (PVDF) coating (Skincerity) containing rapamycin or the PVDF coating alone nightly to fibromatous lesions for a duration of six months. The primary goal of this study is to evaluate the safety of the topical product in patients with TSC and NF1. The secondary goal of this study is to evaluate the effectiveness of the topical product for treatment of cutaneous fibromatous lesions.

Official Title
-----------------
Topical Rapamycin Therapy to Alleviate Cutaneous Manifestations of Tuberous Sclerosis Complex and Neurofibromatosis 1

Conditions
-----------------
Tuberous Sclerosis, Neurofibromatoses, Angiofibroma, Neurofibroma

Intervention / Treatment
-----------------
* Drug: Skincerity
* Drug: Skincerity plus sirolimus/rapamycin
* Drug: Skinercity plus sirolimus/rapamycin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is willing and able to comply with all trial requirements Subject is male or female and over 13 years of age Subject has a diagnosis of either TSC or NF1 and has visible fibromatous lesions (angiofibromas or neurofibromas) Female subjects of child-bearing potential must not be pregnant and must agree to use appropriate contraceptive methods for the duration of the trial Exclusion Criteria: Subject is currently receiving therapy with rapamycin or sirolimus Subject is receiving any form of immunosuppression or has previously experienced immune dysfunction Subject is currently participating in or has participated within the last 30 days in any clinical trial involving an investigational drug Subject has a known hypersensitivity to either the PVDF coating (Skincerity®) or rapamycin Subject is a pregnant or nursing female

Ages Eligible for Study
-----------------
Minimum Age: 13 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: TSC Placebo Arm<br>TSC subjects will apply a study product containing polyvinylidene fluoride coating alone to facial angiofibromas | Drug: Skincerity<br>* Study subjects will apply a study product containing polyvinylidene fluoride coating alone to either facial angiofibromas or cutaneous neurofibromas<br>|
| Experimental: TSC 1% Arm<br>TSC subjects will apply a study product containing polyvinylidene fluoride coating plus 1 mg of sirolimus/rapamycin to facial angiofibromas | Drug: Skincerity plus sirolimus/rapamycin<br>* Study subjects will apply a study product containing polyvinylidene fluoride coating plus 1 mg of sirolimus/rapamycin to either facial angiofibromas or cutaneous neurofibromas<br>|
| Experimental: TSC 5% Arm<br>TSC subjects will apply a study product containing polyvinylidene fluoride coating plus 5 mg of sirolimus/rapamycin to facial angiofibromas | Drug: Skinercity plus sirolimus/rapamycin<br>* Study subjects will apply a study product containing polyvinylidene fluoride coating plus 5 mg of sirolimus/rapamycin to either facial angiofibromas or cutaneous neurofibromas<br>|
| Placebo Comparator: NF1 Placebo Arm<br>NF1 subjects will apply a study product containing polyvinylidene fluoride coating alone to cutaneous neurofibromas | Drug: Skincerity<br>* Study subjects will apply a study product containing polyvinylidene fluoride coating alone to either facial angiofibromas or cutaneous neurofibromas<br>|
| Experimental: NF1 1% Arm<br>NF1 subjects will apply a study product containing polyvinylidene fluoride coating plus 1 mg of sirolimus/rapamycin to cutaneous neurofibromas | Drug: Skincerity plus sirolimus/rapamycin<br>* Study subjects will apply a study product containing polyvinylidene fluoride coating plus 1 mg of sirolimus/rapamycin to either facial angiofibromas or cutaneous neurofibromas<br>|
| Experimental: NF1 5% Arm<br>NF1 subjects will apply a study product containing polyvinylidene fluoride coating plus 5 mg of sirolimus/rapamycin to cutaneous neurofibromas | Drug: Skinercity plus sirolimus/rapamycin<br>* Study subjects will apply a study product containing polyvinylidene fluoride coating plus 5 mg of sirolimus/rapamycin to either facial angiofibromas or cutaneous neurofibromas<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rapamycin level |  | 6 months | 
| Complete blood count |  | 6 months | 
| Total cholesterol |  | 6 months | 
| Dermatologic sensitivity at site of application (pain, erythema, edema, pruritis) |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in lesion size and appearance |  | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Tuberous Sclerosis, Neurofibromatoses, Angiofibroma, Neurofibroma, Sirolimus