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

Phase 2

Completed

• Conditions: Facial Angiofibroma; Tuberous Sclerosis
• Interventions: Drug: placebo; Drug: rapamycin

• Registration Number: NCT03826628
• Lead Sponsor: Dermatology Specialties Limited Partnership

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).

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 Timeline

• Study First Submitted: 2019-01-29
• Study First Submitted QC: 2019-01-30
• Study First Posted: 2019-02-01
• Study Start: 2019-07-28
• Status Verified: 2022-07
• Primary Completion: 2022-09-01
• Study Completion: 2022-09-01
• Results First Submitted: 2023-07-19
• Results First Submitted QC: 2023-08-09
• Results First Posted: 2023-08-14
• Last Update Submitted: 2023-08-17
• Last Update Posted: 2023-09-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 107

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Placebo cream topical, applied once daily before bed on affected area for 26 weeks
1.0% Rapamycin cream, topical	rapamycin	Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks
0.5% Rapamycin cream, topical	rapamycin	Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks

Primary Outcome Measures

Name	Time	Method
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. IGA scores range from 0-4: 0=Clear; 1. Almost Clear; 2. Mild; 3. Moderate; 4. Severe

Secondary Outcome Measures

Name	Time	Method
Subjective (Participant or Parent/Caregiver) Percentage Change Rating Scale	After 26 weeks treatment	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.
Time to Treatment Success	From first dose to 26 weeks (± 2 weeks)	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; 1. Almost Clear; 2. Mild; 3. Moderate; 4. Severe
Change From Baseline in Investigator's Global Assessment	At baseline and after 26 weeks treatment	The change in grading on the Investigator's Global Assessment (IGA) scale from baseline.; IGA scores range from 0-4: 0=Clear; 1. Almost Clear; 2. Mild; 3. Moderate; 4. Severe
Change From Baseline in Facial Angiofibroma Severity Index (FASI)	At baseline and after 26 weeks treatment	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
Objective (Clinician) Percentage Change Rating Scale	After 26 weeks treatment	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.
Categorical Change in Facial Angiofibroma	After 26 weeks treatment	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.

Trial Locations

Locations (17)

University of Pécs; 🇭🇺 Pécs, Hungary

University of California San Diego; 🇺🇸 La Jolla, California, United States

Clinica Universidad de Navarra; 🇪🇸 Pamplona, Navarra, Spain

Clínica Universidad de Navarra; 🇪🇸 Madrid, Spain

Bethesda Children's Hospital of the Hungarian Reformed Church; 🇭🇺 Budapest, Hungary

Fakultni nemocnice Brno; 🇨🇿 Brno, Czechia

Canterbury District Health Board; 🇳🇿 Christchurch, Canterbury, New Zealand

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Phoenix Children's Hospital; 🇺🇸 Phoenix, Arizona, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

All Children's Research Institute; 🇺🇸 Saint Petersburg, Florida, United States

Clinic of Neurology and Psychiatry for Children and Youth; 🇷🇸 Belgrade, Serbia

Narodný ústav detských chorȏb; 🇸🇰 Bratislava, Slovakia

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Clinical Center of Serbia; 🇷🇸 Belgrade, Serbia

Children's Health Queensland; 🇦🇺 Brisbane, Queensland, Australia

Spectrum Health; 🇺🇸 Grand Rapids, Michigan, United States