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

• ClinicalTrials.gov Identifier: NCT03826628
• Recruitment Status: Completed
• First Posted: February 1, 2019
• Last Update Posted: July 28, 2022
• Sponsor: Dermatology Specialties Limited Partnership
• Information provided by (Responsible Party): Dermatology Specialties Limited Partnership

Tracking Information

• First Submitted Date: January 29, 2019
• First Posted Date: February 1, 2019
• Last Update Posted Date: July 28, 2022
• Actual Study Start Date: July 28, 2019
• Actual Primary Completion Date: July 12, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 30, 2019)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 30, 2019)

• Time to treatment success [ Time Frame: From first dose to 26 weeks ]
  The time elapsed from the first dose to the time of treatment success, according to the IGA scale
• Change from baseline in IGA [ Time Frame: At baseline and after 26 weeks treatment ]
  The change in grading on the IGA scale from baseline
• Change from baseline in FASI [ Time Frame: At baseline and after 26 weeks treatment ]
  The change in grading on the Facial Angiofibroma Severity Index (FASI) from baseline
• Subjective (participant or parent/caregiver) improvement rating [ Time Frame: After 26 weeks treatment ]
  Percentage improvement in FA since beginning treatment, as assessed by the participant or parent/caregiver
• Objective (clinician) improvement rating [ Time Frame: After 26 weeks treatment ]
  Percentage improvement in FA since beginning treatment, as assessed by the clinician
• Categorical Change in FA [ Time Frame: After 26 weeks treatment ]
  Change in FA since beginning treatment on a 5-point scale, as assessed by the participant or parent/caregiver

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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 Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

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

Study Arms

• Experimental: 0.5% Rapamycin cream, topical
  Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks
  Intervention: Drug: rapamycin
• Experimental: 1.0% Rapamycin cream, topical
  Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks
  Intervention: Drug: rapamycin
• Placebo Comparator: Placebo
  Placebo cream topical, applied once daily before bed on affected area for 26 weeks
  Intervention: Drug: placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 21, 2022): 107
• Original Estimated Enrollment (submitted: January 30, 2019): 120
• Actual Study Completion Date: July 12, 2022
• Actual Primary Completion Date: July 12, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Czechia, Hungary, New Zealand, Serbia, Slovakia, Spain, Taiwan, United States
• Removed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT03826628
• Other Study ID Numbers: DSLP-01
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Individual Participant Data is not planned to be shared with other researchers

• Current Responsible Party: Dermatology Specialties Limited Partnership
• Original Responsible Party: Same as current
• Current Study Sponsor: Dermatology Specialties Limited Partnership
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Ioana Stanescu; Dermatology Specialties Limited Partnership

• PRS Account: Dermatology Specialties Limited Partnership
• Verification Date: July 2022