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Completed

NCT Number: NCT03826628

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

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).

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Key information

Conditions

Facial Angiofibroma Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hamartoma Heredodegenerative Disorders, Nervous System Malformations of Cortical Development Malformations of Cortical Development, Group I Neoplasms Neoplasms, Multiple Primary Neoplastic Syndromes, Hereditary Nervous System Diseases Nervous System Malformations Neurocutaneous Syndromes Neurodegenerative Diseases Tuberous Sclerosis

Age range

6 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Children's Health Queensland, Brisbane, Queensland, Australia

Loading trial locations.

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male and female patients aged ≥ 6 years and ≤ 65 years on the day informed consent is obtained
  • Patients diagnosed with TSC based on the clinical diagnostic criteria of International Tuberous Sclerosis Complex Consensus Conference 2012 and presenting visible facial angiofibroma
  • An FA severity score of 2 or 3 on the IGA scale
  • Patients or their legal representatives capable of understanding the explanation of the clinical trial and who give written informed consent for participation
  • Patients or their legal representatives able to maintain patient diaries following the instructions of the investigator or sub-investigator

Exclusion criteria

  • Patients who cannot carry out the treatment plan or follow-up assessment
  • Patients with serious skin lesions such as erosions or ulcers
  • Patients with known hypersensitivity to any component of the study product
  • Patients who have received rapamycin/sirolimus, everolimus, or temsirolimus within 3 months of enrolment
  • Patients who received laser therapy or surgical therapy within 6 months prior to trial enrolment
  • Patients who participated in any other clinical trial within 3 months prior to the day of enrolment
  • Patients judged unsuitable for this clinical trial by the investigator or sub-investigator
  • Pregnant or lactating females
  • Sexually active females of childbearing potential not using adequate contraception and sexually active males not using adequate contraception
  • Patients with immune dysfunction or receiving any form of immunosuppression
  • Patients with severe FA, with a score of 4 on the IGA scale
  • Patients with an FA severity score of less than 2 on the IGA scale

Treatment and study plan

Rapamycin

Drug

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

Drug

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

Primary outcomes

  1. Percentage of Participants Obtaining Successful Treatment

    Time frame: 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

    • Almost Clear
    • Mild
    • Moderate
    • Severe

Secondary outcomes

  1. Time to Treatment Success

    Time frame: 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

    • Almost Clear
    • Mild
    • Moderate
    • Severe

  2. Change From Baseline in Investigator's Global Assessment

    Time frame: 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

    • Almost Clear
    • Mild
    • Moderate
    • Severe

  3. Change From Baseline in Facial Angiofibroma Severity Index (FASI)

    Time frame: 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

  4. Subjective (Participant or Parent/Caregiver) Percentage Change Rating Scale

    Time frame: 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.

  5. Objective (Clinician) Percentage Change Rating Scale

    Time frame: 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.

  6. Categorical Change in Facial Angiofibroma

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Dermatology Specialties Limited Partnership

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Feb 1, 2019
Registry last updated
Sep 8, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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