Clinical trial NCT03826628: Dose-Ranging Efficacy and Safety Study of Topical Rapamycin Cream for Facial Angiofibroma Associated With Tuberous Sclerosis Complex
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Facial Angiofibroma
Tuberous Sclerosis
Lead sponsor: Dermatology Specialties Limited Partnership
Sponsor class: INDUSTRY
First posted: 2019-02-01
Enrollment: 107
Sex: ALL
Minimum age (years): 6
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Obtaining Successful Treatment
timeFrame: After 26 weeks treatment
Secondary outcomes:
measure: Time to Treatment Success
timeFrame: From first dose to 26 weeks (± 2 weeks)
measure: Change From Baseline in Investigator's Global Assessment
timeFrame: At baseline and after 26 weeks treatment
measure: Change From Baseline in Facial Angiofibroma Severity Index (FASI)
timeFrame: At baseline and after 26 weeks treatment
measure: Subjective (Participant or Parent/Caregiver) Percentage Change Rating Scale
timeFrame: After 26 weeks treatment
measure: Objective (Clinician) Percentage Change Rating Scale
timeFrame: After 26 weeks treatment
measure: Categorical Change in Facial Angiofibroma
timeFrame: After 26 weeks treatment
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Saint Petersburg
country: United States
facility: All Children's Research Institute
state: Florida
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Brisbane
country: Australia
facility: Children's Health Queensland
state: Queensland
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Budapest
country: Hungary
facility: Bethesda Children's Hospital of the Hungarian Reformed Church
city: Pécs
country: Hungary
facility: University of Pécs
city: Christchurch
country: New Zealand
facility: Canterbury District Health Board
state: Canterbury
city: Belgrade
country: Serbia
facility: Clinic of Neurology and Psychiatry for Children and Youth
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Bratislava
country: Slovakia
facility: Narodný ústav detských chorȏb
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Dermatology Specialties Limited Partnership
name: Ioana Stanescu
role: STUDY_DIRECTOR
References:
citation: 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 cream formulation improves facial angiofibromas associated with tuberous sclerosis complex: a double-blind randomized placebo-controlled trial. Br J Dermatol. 2023 Oct 25;189(5):520-530. doi: 10.1093/bjd/ljad243.