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

Tuberous Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03826628
• Other study ID #: DSLP-01
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 28, 2019
• Est. completion date: September 1, 2022

Study information

• Verified date: July 2022
• Source: Dermatology Specialties Limited Partnership
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 107
• Est. completion date: September 1, 2022
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Angiofibroma
• Facial Angiofibroma
• Facies
• Sclerosis
• Tuberous Sclerosis

Intervention

Drug:
• rapamycin
Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks
• placebo
Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks

Locations

Country	Name	City	State
Australia	Children's Health Queensland	Brisbane	Queensland
Czechia	Fakultni nemocnice Brno	Brno
Hungary	Bethesda Children's Hospital of the Hungarian Reformed Church	Budapest
Hungary	University of Pécs	Pécs
New Zealand	Canterbury District Health Board	Christchurch	Canterbury
Serbia	Clinic of Neurology and Psychiatry for Children and Youth	Belgrade
Serbia	Clinical Center of Serbia	Belgrade
Slovakia	Narodný ústav detských chor?b	Bratislava
Spain	Clínica Universidad de Navarra	Madrid
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Taiwan	National Taiwan University Hospital	Taipei
United States	University of Virginia	Charlottesville	Virginia
United States	Spectrum Health	Grand Rapids	Michigan
United States	University of California San Diego	La Jolla	California
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota
United States	All Children's Research Institute	Saint Petersburg	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Dermatology Specialties Limited Partnership

Countries where clinical trial is conducted

United States,  Australia,  Czechia,  Hungary,  New Zealand,  Serbia,  Slovakia,  Spain,  Taiwan, 

References & Publications (1)

Aitken P, Stanescu I, Boddington L, Mahon C, Fogarasi A, Liao YH, Ivars M, Moreno-Artero E, Trauner D, DeRoos ST, Jancic J, Nikolic M, Balazova P, Price HN, Hadzsiev K, Riney K, Stapleton S, Tollefson MM, Bauer D, Pinkova B, Atkinson H. A novel rapamycin — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Obtaining Successful 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. IGA scores range from 0-4: 0=Clear; Almost Clear; Mild; Moderate; Severe	After 26 weeks treatment
Secondary	Time to Treatment Success	The time elapsed from the first dose to the time of treatment success, according to the Investigator's Global Assessment (IGA) scale. The total time of treatment was 26 weeks, although Covid-19 visit delays led to an extension of up to 2 weeks (28 weeks total) for some patients. 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. IGA scores range from 0-4: 0=Clear; Almost Clear; Mild; Moderate; Severe	From first dose to 26 weeks (± 2 weeks)
Secondary	Change From Baseline in Investigator's Global Assessment	The change in grading on the Investigator's Global Assessment (IGA) scale from baseline.; IGA scores range from 0-4: 0=Clear; Almost Clear; Mild; Moderate; Severe	At baseline and after 26 weeks treatment
Secondary	Change From Baseline in Facial Angiofibroma Severity Index (FASI)	The change in grading on the Facial Angiofibroma Severity Index (FASI) from baseline. FASI grades lesions according to their erythema, size and extent by summing the scores of each category. The final FASI scores range from (mild) 2-9 (severe).; Erythema Skin color 0 Light Red 1 Red 2 Dark Red/purple 3 Size None 0 Small (< 5mm) 1 Large (> 5mm) 2 Confluent 3 Extension <50 % cheek surface 2 >50% cheek surface 3	At baseline and after 26 weeks treatment
Secondary	Subjective (Participant or Parent/Caregiver) Percentage Change Rating Scale	Percentage change in facial angiofibroma since beginning treatment, as assessed by the participant or parent/caregiver. A large value indicates most improvement to facial angiofibroma (minimum=0, maximum=100). This was a single assessment time-point, where the participant or parent/caregiver estimated the percentage change in the facial angiofibroma lesion appearance from their perspective since baseline.	After 26 weeks treatment
Secondary	Objective (Clinician) Percentage Change Rating Scale	Percentage improvement in facial angiofibroma since beginning treatment, as assessed by the clinician. A large value indicates most improvement to facial angiofibroma (minimum=0, maximum=100). This was a single assessment time-point, where clinicians estimated the percentage change in the facial angiofibroma lesion appearance from their perspective since baseline.	After 26 weeks treatment
Secondary	Categorical Change in Facial Angiofibroma	Change in facial angiofibroma since beginning treatment on a 5-point scale, as assessed by the participant or parent/caregiver. This was a single assessment time-point, where the participant or parent/caregiver evaluated the change in the facial angiofibroma lesion appearance from their perspective since baseline.	After 26 weeks treatment