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

Primary Purpose

Facial Angiofibroma, Tuberous Sclerosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
rapamycin
placebo
Sponsored by
Dermatology Specialties Limited Partnership
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Facial Angiofibroma

Eligibility Criteria

6 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Phoenix Children's Hospital
  • University of California San Diego
  • All Children's Research Institute
  • Spectrum Health
  • Mayo Clinic
  • University of Virginia
  • Children's Health Queensland
  • Fakultni nemocnice Brno
  • Bethesda Children's Hospital of the Hungarian Reformed Church
  • University of Pécs
  • Canterbury District Health Board
  • Clinic of Neurology and Psychiatry for Children and Youth
  • Clinical Center of Serbia
  • Narodný ústav detských chorȏb
  • Clinica Universidad de Navarra
  • Clínica Universidad de Navarra
  • National Taiwan University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

0.5% Rapamycin cream, topical

1.0% Rapamycin cream, topical

Placebo

Arm Description

Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks

Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks

Placebo cream topical, applied once daily before bed on affected area for 26 weeks

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
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
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.
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.
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.

Full Information

First Posted
January 29, 2019
Last Updated
August 17, 2023
Sponsor
Dermatology Specialties Limited Partnership
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1. Study Identification

Unique Protocol Identification Number
NCT03826628
Brief Title
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

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
July 28, 2019 (Actual)
Primary Completion Date
September 1, 2022 (Actual)
Study Completion Date
September 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dermatology Specialties Limited Partnership

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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).
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Facial Angiofibroma, Tuberous Sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
107 (Actual)

8. Arms, Groups, and Interventions

Arm Title
0.5% Rapamycin cream, topical
Arm Type
Experimental
Arm Description
Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks
Arm Title
1.0% Rapamycin cream, topical
Arm Type
Experimental
Arm Description
Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo cream topical, applied once daily before bed on affected area for 26 weeks
Intervention Type
Drug
Intervention Name(s)
rapamycin
Other Intervention Name(s)
sirolimus
Intervention Description
Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks
Primary Outcome Measure Information:
Title
Percentage of Participants Obtaining Successful Treatment
Description
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
Time Frame
After 26 weeks treatment
Secondary Outcome Measure Information:
Title
Time to Treatment Success
Description
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
Time Frame
From first dose to 26 weeks (± 2 weeks)
Title
Change From Baseline in Investigator's Global Assessment
Description
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
Time Frame
At baseline and after 26 weeks treatment
Title
Change From Baseline in Facial Angiofibroma Severity Index (FASI)
Description
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
Time Frame
At baseline and after 26 weeks treatment
Title
Subjective (Participant or Parent/Caregiver) Percentage Change Rating Scale
Description
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 Frame
After 26 weeks treatment
Title
Objective (Clinician) Percentage Change Rating Scale
Description
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.
Time Frame
After 26 weeks treatment
Title
Categorical Change in Facial Angiofibroma
Description
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.
Time Frame
After 26 weeks treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ioana Stanescu
Organizational Affiliation
Dermatology Specialties Limited Partnership
Official's Role
Study Director
Facility Information:
Facility Name
Phoenix Children's Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
University of California San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
All Children's Research Institute
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Spectrum Health
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
Children's Health Queensland
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Fakultni nemocnice Brno
City
Brno
ZIP/Postal Code
5HG9+4W
Country
Czechia
Facility Name
Bethesda Children's Hospital of the Hungarian Reformed Church
City
Budapest
ZIP/Postal Code
G39Q+49
Country
Hungary
Facility Name
University of Pécs
City
Pécs
ZIP/Postal Code
H-7624
Country
Hungary
Facility Name
Canterbury District Health Board
City
Christchurch
State/Province
Canterbury
ZIP/Postal Code
8011
Country
New Zealand
Facility Name
Clinic of Neurology and Psychiatry for Children and Youth
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Clinical Center of Serbia
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Narodný ústav detských chorȏb
City
Bratislava
ZIP/Postal Code
83340
Country
Slovakia
Facility Name
Clinica Universidad de Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Clínica Universidad de Navarra
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
National Taiwan University Hospital
City
Taipei
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Individual Participant Data is not planned to be shared with other researchers
Citations:
PubMed Identifier
37463422
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-blinded, randomised, placebo-controlled trial. Br J Dermatol. 2023 Jul 18:ljad243. doi: 10.1093/bjd/ljad243. Online ahead of print.
Results Reference
result

Learn more about this trial

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

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