Trial Outcomes & Findings for Topical Rapamycin to Erase Angiofibromas in TSC (NCT NCT01526356)

Last Updated: 2020-10-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

179 participants

Primary outcome timeframe

baseline, 6 months

Results posted on

2020-10-26

Participant Flow

Participant milestones

Participant milestones
Measure	1% Rapamycin 1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1 % Rapamycin 0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Placebo Cream only Placebo: Study cream is applied nightly to the affected areas on the face.
Overall Study STARTED	59	63	57
Overall Study COMPLETED	51	53	45
Overall Study NOT COMPLETED	8	10	12

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Topical Rapamycin to Erase Angiofibromas in TSC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1% Rapamycin n=59 Participants 1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1 % Rapamycin n=63 Participants 0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Placebo n=57 Participants Cream only Placebo: Study cream is applied nightly to the affected areas on the face.	Total n=179 Participants Total of all reporting groups
Age, Continuous	19.2 years STANDARD_DEVIATION 13.0 • n=93 Participants	21.7 years STANDARD_DEVIATION 12.4 • n=4 Participants	20.3 years STANDARD_DEVIATION 14.3 • n=27 Participants	20.5 years STANDARD_DEVIATION 13.2 • n=483 Participants
Sex: Female, Male Female	36 Participants n=93 Participants	34 Participants n=4 Participants	29 Participants n=27 Participants	99 Participants n=483 Participants
Sex: Female, Male Male	23 Participants n=93 Participants	29 Participants n=4 Participants	28 Participants n=27 Participants	80 Participants n=483 Participants

PRIMARY outcome

Timeframe: baseline, 6 months

Population: This data was not collected for 12 in the 1% rapamycin arm, 17 in the 0.1% rapamycin arm, and 17 in the placebo arm.

Outcome measures

Outcome measures
Measure	1% Rapamycin n=47 Participants 1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1 % Rapamycin n=46 Participants 0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Placebo n=40 Participants Cream only Placebo: Study cream is applied nightly to the affected areas on the face.
Change From Baseline in the Facial Angiofibroma Grading Scale (AGS) Score	-13.89 score on a scale Standard Deviation 20.86	-12.71 score on a scale Standard Deviation 20.24	-1.39 score on a scale Standard Deviation 14.64

SECONDARY outcome

Timeframe: baseline, 6 months

Population: This data was not collected for 4 in the 1% rapamycin arm, 5 in the 0.1% rapamycin arm, and 6 in the placebo arm.

Outcome measures

Outcome measures
Measure	1% Rapamycin n=55 Participants 1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1 % Rapamycin n=58 Participants 0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Placebo n=51 Participants Cream only Placebo: Study cream is applied nightly to the affected areas on the face.
Photo Readers' Rating (Better, Same, or Worse) of Paired Baseline and End-of-trial (EOT) Photographs for Each Patient better	45 Participants	38 Participants	13 Participants
Photo Readers' Rating (Better, Same, or Worse) of Paired Baseline and End-of-trial (EOT) Photographs for Each Patient same	5 Participants	11 Participants	15 Participants
Photo Readers' Rating (Better, Same, or Worse) of Paired Baseline and End-of-trial (EOT) Photographs for Each Patient worse	5 Participants	9 Participants	23 Participants

SECONDARY outcome

Timeframe: baseline, 6 months

Population: This data was not collected for 29 in the 1% rapamycin arm, 34 in the 0.1% rapamycin arm, and 35 in the placebo arm.

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).

Outcome measures

Outcome measures
Measure	1% Rapamycin n=30 Participants 1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1 % Rapamycin n=29 Participants 0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Placebo n=22 Participants Cream only Placebo: Study cream is applied nightly to the affected areas on the face.
Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Dermatology Life Quality Index (DLQI)	-1.5 score on a scale Standard Deviation 4.4	-3.2 score on a scale Standard Deviation 5.0	-1.6 score on a scale Standard Deviation 4.5

SECONDARY outcome

Timeframe: baseline, 6 months

Population: This data was not collected for 46 in the 1% rapamycin arm, 57 in the 0.1% rapamycin arm, and 48 in the placebo arm.

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).

Outcome measures

Outcome measures
Measure	1% Rapamycin n=13 Participants 1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1 % Rapamycin n=6 Participants 0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Placebo n=9 Participants Cream only Placebo: Study cream is applied nightly to the affected areas on the face.
Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Children's Dermatology Life Quality Index (CDLQI)	-0.2 score on a scale Standard Deviation 4.1	-1.7 score on a scale Standard Deviation 3.1	-1.8 score on a scale Standard Deviation 2.6

SECONDARY outcome

Timeframe: baseline, 6 months

Population: This data was not collected for 41 in the 1% rapamycin arm, 35 in the 0.1% rapamycin arm, and 38 in the placebo arm.

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).

Outcome measures

Outcome measures
Measure	1% Rapamycin n=18 Participants 1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1 % Rapamycin n=28 Participants 0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Placebo n=19 Participants Cream only Placebo: Study cream is applied nightly to the affected areas on the face.
Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Family Dermatology Life Quality Index (FDLQI)	-2.2 score on a scale Standard Deviation 3.2	-1.8 score on a scale Standard Deviation 5.2	0.3 score on a scale Standard Deviation 3.4

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

Dermatologic sensitivity includes pain, pruritis, or erythema at the application site.

Outcome measures

Outcome measures
Measure	1% Rapamycin n=59 Participants 1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1 % Rapamycin n=63 Participants 0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Placebo n=57 Participants Cream only Placebo: Study cream is applied nightly to the affected areas on the face.
Number of Events of Dermatologic Sensitivity at the Site of Application Application site pruritis	5 number of events	0 number of events	1 number of events
Number of Events of Dermatologic Sensitivity at the Site of Application Application site erythema	2 number of events	1 number of events	0 number of events
Number of Events of Dermatologic Sensitivity at the Site of Application Application site pain	6 number of events	2 number of events	1 number of events

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

Blood levels checked to confirm the lack of systemic rapamycin.

Outcome measures

Outcome measures
Measure	1% Rapamycin n=59 Participants 1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1 % Rapamycin n=63 Participants 0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Placebo n=57 Participants Cream only Placebo: Study cream is applied nightly to the affected areas on the face.
Number of Participants With Systemic Uptake of Topically Applied Rapamycin	0 Participants	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

0.1 % Rapamycin

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

1% Rapamycin

Serious events: 2 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=59 participants at risk Cream only Placebo: Study cream is applied nightly to the affected areas on the face.	0.1 % Rapamycin n=63 participants at risk 0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	1% Rapamycin n=57 participants at risk 1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose
Hepatobiliary disorders cholecystectomy	0.00% 0/59 • 6 months Serious adverse events were determined to be unrelated to study drug.	0.00% 0/63 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.8% 1/57 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.
Nervous system disorders Subependymal Giant Cell Astrocytoma (SEGA) resection	0.00% 0/59 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.6% 1/63 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.8% 1/57 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.
General disorders Chest pain	1.7% 1/59 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	0.00% 0/63 • 6 months Serious adverse events were determined to be unrelated to study drug.	0.00% 0/57 • 6 months Serious adverse events were determined to be unrelated to study drug.

Other adverse events

Additional Information

Mary Kay Koenig, MD

The University of Texas Health Science Center at Houston

Phone: 713-500-7142

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=59 participants at risk Cream only Placebo: Study cream is applied nightly to the affected areas on the face.	0.1 % Rapamycin n=63 participants at risk 0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	1% Rapamycin n=57 participants at risk 1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose
Skin and subcutaneous tissue disorders Application site pain	1.7% 1/59 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	3.2% 2/63 • Number of events 2 • 6 months Serious adverse events were determined to be unrelated to study drug.	10.5% 6/57 • Number of events 6 • 6 months Serious adverse events were determined to be unrelated to study drug.
Skin and subcutaneous tissue disorders Application site pruritus	1.7% 1/59 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	0.00% 0/63 • 6 months Serious adverse events were determined to be unrelated to study drug.	8.8% 5/57 • Number of events 5 • 6 months Serious adverse events were determined to be unrelated to study drug.
Skin and subcutaneous tissue disorders Application site acne	1.7% 1/59 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.6% 1/63 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	5.3% 3/57 • Number of events 3 • 6 months Serious adverse events were determined to be unrelated to study drug.
Skin and subcutaneous tissue disorders Cutaneous eruption	1.7% 1/59 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	3.2% 2/63 • Number of events 2 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.8% 1/57 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.
Skin and subcutaneous tissue disorders Pruritus	3.4% 2/59 • Number of events 2 • 6 months Serious adverse events were determined to be unrelated to study drug.	3.2% 2/63 • Number of events 2 • 6 months Serious adverse events were determined to be unrelated to study drug.	0.00% 0/57 • 6 months Serious adverse events were determined to be unrelated to study drug.
Skin and subcutaneous tissue disorders Application site erythema	0.00% 0/59 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.6% 1/63 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	3.5% 2/57 • Number of events 2 • 6 months Serious adverse events were determined to be unrelated to study drug.
Skin and subcutaneous tissue disorders Sunburn	0.00% 0/59 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.6% 1/63 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	3.5% 2/57 • Number of events 2 • 6 months Serious adverse events were determined to be unrelated to study drug.
Skin and subcutaneous tissue disorders Application site irritation	0.00% 0/59 • 6 months Serious adverse events were determined to be unrelated to study drug.	3.2% 2/63 • Number of events 2 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.8% 1/57 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.
Skin and subcutaneous tissue disorders Acne	1.7% 1/59 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	3.2% 2/63 • Number of events 2 • 6 months Serious adverse events were determined to be unrelated to study drug.	0.00% 0/57 • 6 months Serious adverse events were determined to be unrelated to study drug.
Infections and infestations Nasopharyngitis	0.00% 0/59 • 6 months Serious adverse events were determined to be unrelated to study drug.	0.00% 0/63 • 6 months Serious adverse events were determined to be unrelated to study drug.	3.5% 2/57 • Number of events 2 • 6 months Serious adverse events were determined to be unrelated to study drug.
Infections and infestations Nasal congestion	0.00% 0/59 • 6 months Serious adverse events were determined to be unrelated to study drug.	0.00% 0/63 • 6 months Serious adverse events were determined to be unrelated to study drug.	3.5% 2/57 • Number of events 2 • 6 months Serious adverse events were determined to be unrelated to study drug.
Skin and subcutaneous tissue disorders Application site papules	0.00% 0/59 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.6% 1/63 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.8% 1/57 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.
Infections and infestations Sinusitis	0.00% 0/59 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.6% 1/63 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.8% 1/57 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.
Skin and subcutaneous tissue disorders Application site paraesthesia	1.7% 1/59 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	0.00% 0/63 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.8% 1/57 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.
Gastrointestinal disorders Nausea	0.00% 0/59 • 6 months Serious adverse events were determined to be unrelated to study drug.	3.2% 2/63 • Number of events 2 • 6 months Serious adverse events were determined to be unrelated to study drug.	0.00% 0/57 • 6 months Serious adverse events were determined to be unrelated to study drug.
General disorders Mouth ulceration	1.7% 1/59 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.6% 1/63 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	0.00% 0/57 • 6 months Serious adverse events were determined to be unrelated to study drug.
Respiratory, thoracic and mediastinal disorders Cough	1.7% 1/59 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	1.6% 1/63 • Number of events 1 • 6 months Serious adverse events were determined to be unrelated to study drug.	0.00% 0/57 • 6 months Serious adverse events were determined to be unrelated to study drug.