Topical Rapamycin to Erase Angiofibromas in TSC

Study Overview
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Brief Summary
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The study is a multi-center prospective, randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of a topically applied formulation of rapamycin to cutaneous angiofibromas in subjects with Tuberous Sclerosis Complex (TSC). Subjects will apply either the topical vehicle containing rapamycin or the topical vehicle alone nightly to their angiofibromas for six months. The primary goal of this study is to evaluate the efficacy of the topical medication for reduction of cutaneous angiofibromas in patients with TSC. The secondary goal of this study is to confirm the safety of the topical medication.

Official Title
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Phase II Study of Topical Rapamycin to Erase Angiofibromas in TSC-Multicenter Evaluation of a Novel Therapy

Conditions
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Angiofibromas, Tuberous Sclerosis

Intervention / Treatment
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* Drug: Placebo
* Drug: Rapamycin
* Drug: Rapamycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be willing and able to comply with all trial requirements. Subject has a diagnosis of TSC and has visible facial angiofibromas. Female subjects of child bearing potential must not be pregnant and must agree to use appropriate contraceptive methods . Exclusion Criteria: Subject is currently receiving therapy with Rapamycin. 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 a clinical trial involving an investigational drug. Subject has a known hypersensitivity to either the vehicle or Rapamycin. Subject is a pregnant or nursing female. Subject has other dermatologic conditions that would preclude or prevent adequate assessment of changes to their facial angiofibromas. Subject has had laser surgery, cryotherapy, or other dermatologic treatment to their facial angiofibromas within the previous 6 months.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Cream only | Drug: Placebo<br>* Study cream is applied nightly to the affected areas on the face.<br>* Other names: Rapamycin;|
| Active Comparator: 0.1 % Rapamycin<br>0.1% Rapamycin cream | Drug: Rapamycin<br>* Study cream is applied nightly to the affected areas on the face. Low Dose<br>|
| Active Comparator: 1% Rapamycin<br>1% Rapamycin cream | Drug: Rapamycin<br>* Study cream is applied nightly to the affected areas on the face. High Dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Facial Angiofibroma Grading Scale (AGS) Score | Subject's lesion/s will be digitally photographed before initial application (visit 1), at each study visit (visits 2 through 6), and immediately prior to study termination (visit 7). Following completion of the study, all photographs will be evaluated by two independent dermatologists blinded to both the treatment arm and the stage of treatment. The dermatologists will assess each photograph's appearance using the facial Angiofibroma Grading Scale (AGS), which assesses the forehead, nose, cheeks, and chin for erythema, average lesion size, lesion density, and percent involvement, as well as presence of any pedunculated angiofibromas. A total score is reported with a range of 0 to 202, with higher scores representing a worse outcome. | baseline, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Photo Readers' Rating (Better, Same, or Worse) of Paired Baseline and End-of-trial (EOT) Photographs for Each Patient |  | baseline, 6 months | 
| Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Dermatology Life Quality Index (DLQI) | The Dermatology life Quality Index (DLQI) is a ten-question questionnaire used to measure the impact of skin disease on the quality of life of an affected person. It is designed for people aged 16 years and above. Each question is scored from 0 to 3, giving a possible total score range from 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life). | baseline, 6 months | 
| Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Children's Dermatology Life Quality Index (CDLQI) | The Children's Dermatology life Quality Index (DLQI) is validated from the age of four years to 16 years. It is a ten-question questionnaire used to measure the impact of skin disease on the quality of life of an affected person. Each question is scored from 0 to 3, giving a possible total score range from 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life). | baseline, 6 months | 
| Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Family Dermatology Life Quality Index (FDLQI) | The Family Dermatology life Quality Index (FLQI) is designed for adult (more than 16 years of age) family members or partners of patients (of any age) with any skin disease. It is a ten-question questionnaire used to measure the impact of skin disease on the quality of life of an affected person. Each question is scored from 0 to 3, giving a possible total score range from 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life). | baseline, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mTOR, Angiofibroma, Tuberous Sclerosis, Rapamycin, Sirolimus