Topical Sirolimus Ointment for Cutaneous Angiofibromas in Subjects With Tuberous Sclerosis Complex

NCT ID: NCT03363763

Last Updated: 2025-12-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-12
• Study Completion Date: 2023-03-24

Brief Summary

The objective of this study is to evaluate the safety and efficacy of sirolimus (0.2% and 0.4% formulations) and its vehicle when applied topically once daily for 12 weeks for the treatment of cutaneous angiofibromas in pediatric subjects with tuberous sclerosis complex (TSC).

Detailed Description

This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study designed to assess the safety and efficacy of topically-applied sirolimus for the treatment of cutaneous angiofibromas in pediatric subjects with TSC. Approximately 45 subjects will be enrolled at investigational sites in the United States (US) and China, though other countries may be added in the future. Approximately 45 subjects who meet the study entry criteria will randomly be assigned in a 1:1:1 ratio to receive 1 of 3 treatments: sirolimus 0.2% ointment, sirolimus 0.4% ointment, or placebo ointment. The randomization is stratified by site. Subjects, or a parent/guardian, will apply the study medication topically to the cutaneous angiofibromas on the face once daily at night before going to bed for 12 weeks. Subjects who complete the double-blind phase of the study, with an overall compliance rate >80% as determined by the dosing diary, will be offered entry into an open-label period for an additional 12 weeks.

The maximum study duration for each subject will be approximately 30 weeks and includes a screening period of up to 4 weeks, a blinded treatment period of 12 weeks, optional open-label period of 12 weeks, and a follow-up period of 2 weeks.

An interim analysis will be performed when all subjects have completed the double-blind phase (Visit 5 - Week 12). The data will be unblinded to assess for efficacy and results reported.

Conditions

Angiofibroma of Face; Tuberous Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sirolimus 0.2%

Sirolimus 0.2% ointment applied topically hs x 12 weeks

Group Type: ACTIVE_COMPARATOR

Sirolimus 0.2%

Intervention Type: DRUG

Ointment for topical administration hs x 12 weeks

Sirolimus 0.4%

Sirolimus 0.4% ointment applied topically hs x 12 weeks

Group Type: ACTIVE_COMPARATOR

Sirolimus 0.4%

Intervention Type: DRUG

Ointment for topical administration hs x 12 weeks

Placebo

Placebo ointment applied topically hs x 12 weeks

Group Type: PLACEBO_COMPARATOR

Placebo ointment

Intervention Type: DRUG

Placebo ointment comparator for topical administration hs x 12 weeks

Interventions

Sirolimus 0.2%

Ointment for topical administration hs x 12 weeks

Intervention Type: DRUG

Sirolimus 0.4%

Ointment for topical administration hs x 12 weeks

Intervention Type: DRUG

Placebo ointment

Placebo ointment comparator for topical administration hs x 12 weeks

Intervention Type: DRUG

Other Intervention Names

Rapamune; rapamycin; mTOR inhibitor; Rapamune; rapamycin; mTOR inhibitor; Placebo

Eligibility Criteria

Inclusion Criteria

1. Generally healthy males or non-pregnant females aged 2 to 21 years, inclusive, at the time of screening.

2. Diagnosis of TSC with visible facial angiofibromas of at least grade 3 up to grade 5, inclusive, based on the IGA.

3. Subjects with 3 or more isolated, measurable lesions of facial angiofibroma, with color grading score ≥2 for each of the 3 lesions.

4. Females of childbearing potential must have a negative urine pregnancy test (or a negative serum pregnancy test if a urine pregnancy test cannot be obtained) (For China, different pregnancy test would be followed) and if sexually active or become sexually active during the study, must agree to use an effective form of birth control for the duration of the study. Females using oral contraceptives must also use a barrier method of contraception during the study. Sexually active male subjects and/or their female partners should also use appropriate contraception.

Effective contraception is defined as follows:

• Oral/implant/injectable/transdermal/estrogenic vaginal ring contraceptives, intrauterine device, condom with spermicide, diaphragm with spermicide.
• Abstinence or partner's vasectomy are acceptable if the female agrees to implement one of the other acceptable methods of birth control if her partner changes.

5. The subject and/or their parent or guardian must be willing and able to provide written informed consent/assent.

6. Willing and able to comply with all trial requirements.

7. Subject or parent/guardian must be able to complete the subject self-assessment survey and subject diary in English or another language into which the documents have been officially translated.

8. Subjects should be in good general health based on the subject's medical history, physical exam, and impression of the study doctor.

Exclusion Criteria

9. Has any chronic or acute medical condition, that in the opinion of the investigator, may pose a risk to the safety of the subject during the trial period, or may interfere with the assessment of safety or efficacy in this trial.

10. Has received oral therapy or topical therapy of an mTOR inhibitor (sirolimus, temsirolimus, or everolimus) within 1 month of Baseline or other dermatological treatment to facial angiofibromas within 1 month of baseline. (Sunscreen is expected to be used in this patient population and is not considered treatment.)

11. Is currently receiving any form of immunosuppression therapy or has previously experienced significant immune dysfunction.

12. Has a history of sensitivity to any component of the investigational product.

13. Is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.

14. Has other dermatologic conditions, pigmentation, scarring, pigmented lesions or sunburn in the treatment area that would preclude or prevent adequate assessment of changes to their facial angiofibromas.

15. Has facial hair (e.g., beard, sideburns, mustache) that could interfere with study assessments.

16. Has had laser surgery or cryotherapy to facial angiofibromas within 6 months preceding study entry.

17. Requires the use of any concomitant medication that, in the investigator's opinion, has the potential to cause an adverse effect when given with the investigational product or will interfere with the interpretation of the study results (see Section 16.1 Appendix 1 for Potential Drug Interactions).

18. Has participated in another clinical trial or received an investigational product within 3 months prior to screening.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aucta Pharmaceuticals, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shoufeng Li, Ph.D

Role: STUDY_DIRECTOR

Aucta Pharmaceuticals, Inc

Locations

Translational Genomics Research

Phoenix, Arizona, United States

Children's Hospital of Los Angeles, Division of Neurology

Los Angeles, California, United States

Children's Clinical Research Organization, Children's Hospital Colorado

Aurora, Colorado, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

LeBonheur Children's Hospital

Memphis, Tennessee, United States

Children's Hospital of Fudan University

Shanghai, , China

Countries

United States; China

References

Koenig MK, Hebert AA, Roberson J, Samuels J, Slopis J, Woerner A, Northrup H. Topical rapamycin therapy to alleviate the cutaneous manifestations of tuberous sclerosis complex: a double-blind, randomized, controlled trial to evaluate the safety and efficacy of topically applied rapamycin. Drugs R D. 2012 Sep 1;12(3):121-6. doi: 10.2165/11634580-000000000-00000.

Reference Type: BACKGROUND

PMID: 22934754 (View on PubMed)

Wheless JW, Almoazen H. A novel topical rapamycin cream for the treatment of facial angiofibromas in tuberous sclerosis complex. J Child Neurol. 2013 Jul;28(7):933-6. doi: 10.1177/0883073813488664. Epub 2013 May 16.

Reference Type: BACKGROUND

PMID: 23680945 (View on PubMed)

Wataya-Kaneda M, Tanaka M, Nakamura A, Matsumoto S, Katayama I. A topical combination of rapamycin and tacrolimus for the treatment of angiofibroma due to tuberous sclerosis complex (TSC): a pilot study of nine Japanese patients with TSC of different disease severity. Br J Dermatol. 2011 Oct;165(4):912-6. doi: 10.1111/j.1365-2133.2011.10471.x.

Reference Type: BACKGROUND

PMID: 21692771 (View on PubMed)

Tanaka M, Wataya-Kaneda M, Nakamura A, Matsumoto S, Katayama I. First left-right comparative study of topical rapamycin vs. vehicle for facial angiofibromas in patients with tuberous sclerosis complex. Br J Dermatol. 2013 Dec;169(6):1314-8. doi: 10.1111/bjd.12567.

Reference Type: BACKGROUND

PMID: 23909960 (View on PubMed)

Rapamune (sirolimus) complete prescribing information. Wyeth Pharmaceuticals Inc. October 2009

Reference Type: BACKGROUND

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

AUCTA-UAP006-PH2

Identifier Type: -

Identifier Source: org_study_id