Dose-Ranging Efficacy and Safety Study of Topical Rapamycin Cream for Facial Angiofibroma Associated With Tuberous Sclerosis Complex

• Sponsor: Dermatology Specialties Limited Partnership (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03826628
• Collaborator: (none)
• Enrollment: 107
• Locations: 17
• Arms: 3
• Actual Duration (Months): 35.5
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The study aims to compare the safety and efficacy of two different strengths of Rapamycin cream, topical and placebo over 26 weeks in the treatment of facial angiofibroma (FA) associated with Tuberous Sclerosis Complex (TSC).

Condition or Disease	Intervention/Treatment	Phase
Facial Angiofibroma; Tuberous Sclerosis	Drug: rapamycin; Drug: placebo	Phase 2/Phase 3

Detailed Description

Topical rapamycin has previously been used to treat FA associated with TSC, reducing erythema, papule size, while flattening lesions and improving skin texture. Topical rapamycin has been reported to be well tolerated.

The efficacy and safety of a topical rapamycin cream at two strengths (0.5% and 1.0%) will be assessed during a 26 week double-blind treatment phase with assessments made at clinical visits at baseline, 2, 8, 14, 20 and 26 weeks, and at follow-up (4 weeks after the last dose of study drug).

Study Design

• Study Type: Interventional
• Actual Enrollment: 107 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2/3, Multi-Center, Double-Blind, Placebo-Controlled, Randomized, Parallel-Group, Dose-Response Comparison of the Efficacy and Safety of a Topical Rapamycin Cream for the Treatment of Facial Angiofibromas (FA) Associated With Tuberous Sclerosis Complex (TSC) in Patients 6 Years of Age and Over
• Actual Study Start Date: Jul 28, 2019
• Actual Primary Completion Date: Jul 12, 2022
• Actual Study Completion Date: Jul 12, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0.5% Rapamycin cream, topical Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks	Drug: rapamycin; Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks; Other Names: sirolimus
Experimental: 1.0% Rapamycin cream, topical Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks	Drug: rapamycin; Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks; Other Names: sirolimus
Placebo Comparator: Placebo Placebo cream topical, applied once daily before bed on affected area for 26 weeks	Drug: placebo; Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks

Outcome Measures

Primary Outcome Measures

1. Percentage of participants obtaining successful treatment [After 26 weeks treatment]

   Success on the Investigator Global Assessment (IGA) scale is defined as clear or almost clear with an improvement of at least two grades from baseline

Secondary Outcome Measures

1. Time to treatment success [From first dose to 26 weeks]

   The time elapsed from the first dose to the time of treatment success, according to the IGA scale

2. Change from baseline in IGA [At baseline and after 26 weeks treatment]

   The change in grading on the IGA scale from baseline

3. Change from baseline in FASI [At baseline and after 26 weeks treatment]

   The change in grading on the Facial Angiofibroma Severity Index (FASI) from baseline

4. Subjective (participant or parent/caregiver) improvement rating [After 26 weeks treatment]

   Percentage improvement in FA since beginning treatment, as assessed by the participant or parent/caregiver

5. Objective (clinician) improvement rating [After 26 weeks treatment]

   Percentage improvement in FA since beginning treatment, as assessed by the clinician

6. Categorical Change in FA [After 26 weeks treatment]

   Change in FA since beginning treatment on a 5-point scale, as assessed by the participant or parent/caregiver

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male and female patients aged ≥ 6 years and ≤ 65 years on the day informed consent is obtained

2. Patients diagnosed with TSC based on the clinical diagnostic criteria of International Tuberous Sclerosis Complex Consensus Conference 2012 and presenting visible facial angiofibroma

3. An FA severity score of 2 or 3 on the IGA scale

4. Patients or their legal representatives capable of understanding the explanation of the clinical trial and who give written informed consent for participation

5. Patients or their legal representatives able to maintain patient diaries following the instructions of the investigator or sub-investigator

Exclusion Criteria:

1. Patients who cannot carry out the treatment plan or follow-up assessment

2. Patients with serious skin lesions such as erosions or ulcers

3. Patients with known hypersensitivity to any component of the study product

4. Patients who have received rapamycin/sirolimus, everolimus, or temsirolimus within 3 months of enrolment

5. Patients who received laser therapy or surgical therapy within 6 months prior to trial enrolment

6. Patients who participated in any other clinical trial within 3 months prior to the day of enrolment

7. Patients judged unsuitable for this clinical trial by the investigator or sub-investigator

8. Pregnant or lactating females

9. Sexually active females of childbearing potential not using adequate contraception and sexually active males not using adequate contraception

10. Patients with immune dysfunction or receiving any form of immunosuppression

11. Patients with severe FA, with a score of 4 on the IGA scale

12. Patients with an FA severity score of less than 2 on the IGA scale

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	University of California San Diego	La Jolla	California	United States	92037
3	All Children's Research Institute	Saint Petersburg	Florida	United States	33701
4	Spectrum Health	Grand Rapids	Michigan	United States	49503
5	Mayo Clinic	Rochester	Minnesota	United States	55905
6	University of Virginia	Charlottesville	Virginia	United States	22903
7	Children's Health Queensland	Brisbane	Queensland	Australia	4101
8	Fakultni nemocnice Brno	Brno		Czechia	5HG9+4W
9	Bethesda Children's Hospital of the Hungarian Reformed Church	Budapest		Hungary	G39Q+49
10	University of Pécs	Pécs		Hungary	H-7624
11	Canterbury District Health Board	Christchurch	Canterbury	New Zealand	8011
12	Clinic of Neurology and Psychiatry for Children and Youth	Belgrade		Serbia	11000
13	Clinical Center of Serbia	Belgrade		Serbia	11000
14	Narodný ústav detských chorȏb	Bratislava		Slovakia	83340
15	Clinica Universidad de Navarra	Pamplona	Navarra	Spain	31008
16	Clínica Universidad de Navarra	Madrid		Spain	28007
17	National Taiwan University Hospital	Taipei		Taiwan

Sponsors and Collaborators

• Dermatology Specialties Limited Partnership

Investigators

• Study Director: Ioana Stanescu, Dermatology Specialties Limited Partnership

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dermatology Specialties Limited Partnership
• ClinicalTrials.gov Identifier: NCT03826628
• Other Study ID Numbers: DSLP-01
• First Posted: Feb 1, 2019
• Last Update Posted: Jul 28, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Tuberous Sclerosis; Angiofibroma; Sclerosis; Facies; Sirolimus

Study Results

No Results Posted as of Jul 28, 2022