Treatment: Topical Rapamycin to Erase Angiofibromas in TSC

• Sponsor: The University of Texas Health Science Center, Houston (Other)
• Overall Status: Completed
• CT.gov ID: NCT01526356
• Collaborator: (none)
• Enrollment: 179
• Locations: 10
• Arms: 3
• Duration (Months): 27
• Patients Per Site: 17.9
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Angiofibromas; Tuberous Sclerosis	Drug: Placebo; Drug: Rapamycin; Drug: Rapamycin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 179 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Topical Rapamycin to Erase Angiofibromas in TSC-Multicenter Evaluation of a Novel Therapy
• Study Start Date: May 1, 2012
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Cream only	Drug: Placebo; Study cream is applied nightly to the affected areas on the face.; Other Names: Rapamycin
Active Comparator: 0.1 % Rapamycin 0.1% Rapamycin cream	Drug: Rapamycin; Study cream is applied nightly to the affected areas on the face. Low Dose
Active Comparator: 1% Rapamycin 1% Rapamycin cream	Drug: Rapamycin; Study cream is applied nightly to the affected areas on the face. High Dose

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Photo Readers' Rating (Better, Same, or Worse) of Paired Baseline and End-of-trial (EOT) Photographs for Each Patient [baseline, 6 months]

2. 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).

3. 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).

4. 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 Outcome Measures

1. Number of Events of Dermatologic Sensitivity at the Site of Application [6 months]

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

2. Number of Participants With Systemic Uptake of Topically Applied Rapamycin [6 months]

   Blood levels checked to confirm the lack of systemic rapamycin.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	UCLA Mattel Children's Hospital	Los Angeles	California	United States	90095
3	Jack & Julia Center for TSC at Oakland Children's Hospital & Research Center	Oakland	California	United States	94609
4	Kennedy Krieger Institute	Baltimore	Maryland	United States	21205
5	Herscot Center for Adults and Children with TSC Massachusetts General Hospital	Boston	Massachusetts	United States	02114
6	Clinic Without Walls	Saint Paul	Minnesota	United States	55102-2697
7	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
8	Texas Scottish Rite Hospital	Dallas	Texas	United States	75219
9	The University of Texas Medical School at Houston	Houston	Texas	United States	77030
10	Sydney Children's Hospital	Sydney	New South Wales	Australia

Sponsors and Collaborators

• The University of Texas Health Science Center, Houston

Investigators

• Principal Investigator: Mary Kay Koenig, MD, The University of Texas Medical School at Houston
• Principal Investigator: Hope Northrup, MD, The University of Texas Medical School at Houston

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mary Kay Koenig, Associate Professor, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT01526356
• Other Study ID Numbers: HSC-MS-11-0501; Department of Defense USAMRMC
• First Posted: Feb 3, 2012
• Last Update Posted: Oct 26, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by Mary Kay Koenig, Associate Professor, The University of Texas Health Science Center, Houston: Angiofibroma; Tuberous Sclerosis; Rapamycin; Sirolimus; mTOR
• Additional relevant MeSH terms: Tuberous Sclerosis; Angiofibroma; Sclerosis; Sirolimus

Study Results

Participant Flow

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

Baseline Characteristics

Arm/Group Title	1% Rapamycin	0.1 % Rapamycin	Placebo	Total
Arm/Group Description	1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Cream only Placebo: Study cream is applied nightly to the affected areas on the face.	Total of all reporting groups
Overall Participants	59	63	57	179
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	19.2 (13.0)	21.7 (12.4)	20.3 (14.3)	20.5 (13.2)
Sex: Female, Male (Count of Participants)
Female	36 61%	34 54%	29 50.9%	99 55.3%
Male	23 39%	29 46%	28 49.1%	80 44.7%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	1% Rapamycin	0.1 % Rapamycin	Placebo
Arm/Group Description	1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Cream only Placebo: Study cream is applied nightly to the affected areas on the face.
Measure Participants	47	46	40
Mean (Standard Deviation) [score on a scale]	-13.89 (20.86)	-12.71 (20.24)	-1.39 (14.64)

2. Secondary Outcome

Title	Photo Readers' Rating (Better, Same, or Worse) of Paired Baseline and End-of-trial (EOT) Photographs for Each Patient
Time Frame	baseline, 6 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	1% Rapamycin	0.1 % Rapamycin	Placebo
Arm/Group Description	1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Cream only Placebo: Study cream is applied nightly to the affected areas on the face.
Measure Participants	55	58	51
better	45 76.3%	38 60.3%	13 22.8%
same	5 8.5%	11 17.5%	15 26.3%
worse	5 8.5%	9 14.3%	23 40.4%

3. Secondary Outcome

Title	Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Dermatology Life Quality Index (DLQI)
Description	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).
Time Frame	baseline, 6 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	1% Rapamycin	0.1 % Rapamycin	Placebo
Arm/Group Description	1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Cream only Placebo: Study cream is applied nightly to the affected areas on the face.
Measure Participants	30	29	22
Mean (Standard Deviation) [score on a scale]	-1.5 (4.4)	-3.2 (5.0)	-1.6 (4.5)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	1% Rapamycin	0.1 % Rapamycin	Placebo
Arm/Group Description	1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Cream only Placebo: Study cream is applied nightly to the affected areas on the face.
Measure Participants	13	6	9
Mean (Standard Deviation) [score on a scale]	-0.2 (4.1)	-1.7 (3.1)	-1.8 (2.6)

5. Secondary Outcome

Title	Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Family Dermatology Life Quality Index (FDLQI)
Description	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).
Time Frame	baseline, 6 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	1% Rapamycin	0.1 % Rapamycin	Placebo
Arm/Group Description	1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Cream only Placebo: Study cream is applied nightly to the affected areas on the face.
Measure Participants	18	28	19
Mean (Standard Deviation) [score on a scale]	-2.2 (3.2)	-1.8 (5.2)	0.3 (3.4)

6. Other Pre-specified Outcome

Title	Number of Events of Dermatologic Sensitivity at the Site of Application
Description	Dermatologic sensitivity includes pain, pruritis, or erythema at the application site.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	0.1 % Rapamycin	1% Rapamycin
Arm/Group Description	Cream only Placebo: Study cream is applied nightly to the affected areas on the face.	0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose
Measure Participants	59	63	57
Application site pain	6	2	1
Application site pruritis	5	0	1
Application site erythema	2	1	0

7. Other Pre-specified Outcome

Title	Number of Participants With Systemic Uptake of Topically Applied Rapamycin
Description	Blood levels checked to confirm the lack of systemic rapamycin.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1% Rapamycin	0.1 % Rapamycin	Placebo
Arm/Group Description	1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose	0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose	Cream only Placebo: Study cream is applied nightly to the affected areas on the face.
Measure Participants	59	63	57
Count of Participants [Participants]	0 0%	0 0%	0 0%

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	Serious adverse events were determined to be unrelated to study drug.
Arm/Group Title	Placebo		0.1 % Rapamycin		1% Rapamycin
Arm/Group Description	Cream only Placebo: Study cream is applied nightly to the affected areas on the face.		0.1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. Low Dose		1% Rapamycin cream Rapamycin: Study cream is applied nightly to the affected areas on the face. High Dose
All Cause Mortality
	Placebo		0.1 % Rapamycin		1% Rapamycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/59 (0%)		0/63 (0%)		0/57 (0%)
Serious Adverse Events
	Placebo		0.1 % Rapamycin		1% Rapamycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/59 (1.7%)		1/63 (1.6%)		2/57 (3.5%)
General disorders
Chest pain	1/59 (1.7%)	1	0/63 (0%)	0	0/57 (0%)	0
Hepatobiliary disorders
cholecystectomy	0/59 (0%)	0	0/63 (0%)	0	1/57 (1.8%)	1
Nervous system disorders
Subependymal Giant Cell Astrocytoma (SEGA) resection	0/59 (0%)	0	1/63 (1.6%)	1	1/57 (1.8%)	1
Other (Not Including Serious) Adverse Events
	Placebo		0.1 % Rapamycin		1% Rapamycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/59 (16.9%)		18/63 (28.6%)		22/57 (38.6%)
Gastrointestinal disorders
Nausea	0/59 (0%)	0	2/63 (3.2%)	2	0/57 (0%)	0
General disorders
Mouth ulceration	1/59 (1.7%)	1	1/63 (1.6%)	1	0/57 (0%)	0
Infections and infestations
Nasopharyngitis	0/59 (0%)	0	0/63 (0%)	0	2/57 (3.5%)	2
Nasal congestion	0/59 (0%)	0	0/63 (0%)	0	2/57 (3.5%)	2
Sinusitis	0/59 (0%)	0	1/63 (1.6%)	1	1/57 (1.8%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/59 (1.7%)	1	1/63 (1.6%)	1	0/57 (0%)	0
Skin and subcutaneous tissue disorders
Application site pain	1/59 (1.7%)	1	2/63 (3.2%)	2	6/57 (10.5%)	6
Application site pruritus	1/59 (1.7%)	1	0/63 (0%)	0	5/57 (8.8%)	5
Application site acne	1/59 (1.7%)	1	1/63 (1.6%)	1	3/57 (5.3%)	3
Cutaneous eruption	1/59 (1.7%)	1	2/63 (3.2%)	2	1/57 (1.8%)	1
Pruritus	2/59 (3.4%)	2	2/63 (3.2%)	2	0/57 (0%)	0
Application site erythema	0/59 (0%)	0	1/63 (1.6%)	1	2/57 (3.5%)	2
Sunburn	0/59 (0%)	0	1/63 (1.6%)	1	2/57 (3.5%)	2
Application site irritation	0/59 (0%)	0	2/63 (3.2%)	2	1/57 (1.8%)	1
Acne	1/59 (1.7%)	1	2/63 (3.2%)	2	0/57 (0%)	0
Application site papules	0/59 (0%)	0	1/63 (1.6%)	1	1/57 (1.8%)	1
Application site paraesthesia	1/59 (1.7%)	1	0/63 (0%)	0	1/57 (1.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.