Topical Rapamycin to Erase Angiofibromas in TSC

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01526356

Acronym

Treatment

Enrollment

179

Registered

2012-02-03

Start date

2012-05-31

Completion date

2014-08-31

Last updated

2020-10-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Angiofibromas, Tuberous Sclerosis

Keywords

Angiofibroma, Tuberous Sclerosis, Rapamycin, Sirolimus, mTOR

Brief summary

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.

Interventions

DRUGPlacebo

Study cream is applied nightly to the affected areas on the face.

DRUGRapamycin

Study cream is applied nightly to the affected areas on the face. Low Dose

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in the Facial Angiofibroma Grading Scale (AGS) Score	baseline, 6 months	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.

Secondary

Measure	Time frame	Description
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)	baseline, 6 months	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).
Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Children's Dermatology Life Quality Index (CDLQI)	baseline, 6 months	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).
Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Family Dermatology Life Quality Index (FDLQI)	baseline, 6 months	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).

Other

Measure	Time frame	Description
Number of Events of Dermatologic Sensitivity at the Site of Application	6 months	Dermatologic sensitivity includes pain, pruritis, or erythema at the application site.
Number of Participants With Systemic Uptake of Topically Applied Rapamycin	6 months	Blood levels checked to confirm the lack of systemic rapamycin.

Countries

Australia, United States

Participant flow

Participants by arm

Arm	Count
1% Rapamycin 1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	59
0.1 % Rapamycin 0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	63
Placebo Cream only Placebo: Study cream is applied nightly to the affected areas on the face.	57
Total	179

Baseline characteristics

Characteristic	1% Rapamycin	0.1 % Rapamycin	Placebo	Total
Age, Continuous	19.2 years STANDARD_DEVIATION 13	21.7 years STANDARD_DEVIATION 12.4	20.3 years STANDARD_DEVIATION 14.3	20.5 years STANDARD_DEVIATION 13.2
Sex: Female, Male Female	36 Participants	34 Participants	29 Participants	99 Participants
Sex: Female, Male Male	23 Participants	29 Participants	28 Participants	80 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 59	0 / 63	0 / 57
other Total, other adverse events	10 / 59	18 / 63	22 / 57
serious Total, serious adverse events	1 / 59	1 / 63	2 / 57

Outcome results

Primary

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.