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

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Brief Title

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

Official Title

Phase 2 Multi Center Prospective Rand. Double Blind Placebo Cont. Parallel Design Study to Evaluate Safety & Efficacy of Topical Sirolimus for Cutaneous Angiofibromas in Subjects W/ Tuberous Sclerosis Complex Followed by Opt. Open Label

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

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.

Study Phase

Phase 2

Study Type


Primary Outcome

The proportion of subjects with a clinical response of treatment success.

Secondary Outcome

 The proportion of subjects with at least 30% improvement at Week 12 as compared to Baseline in the Facial Angiofibromas Severity Index (FASI) score.


Angiofibroma of Face


Sirolimus 0.2%

Study Arms / Comparison Groups

 Arm 1
Description:  Sirolimus 0.2% ointment applied topically hs x 12 weeks


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

April 12, 2017

Completion Date

March 2023

Primary Completion Date

December 2022

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

          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

         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

         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.




2 Years - 21 Years

Accepts Healthy Volunteers



Shoufeng Li, Ph.D, 732-652-9225, [email protected]

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Aucta Pharmaceuticals, Inc

Study Sponsor

Shoufeng Li, Ph.D, Study Director, Aucta Pharmaceuticals, Inc

Verification Date

February 2022