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

NCT03363763 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: AUCTA-UAP006-PH2
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 8

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).

Conditions

Angiofibroma of Face; Tuberous Sclerosis

Keywords

rash; fibroma; skin; facial; face; bumps; redness; erythema; lesions; papules; blood vessel; cheeks

Outcome Measures

Primary Outcomes (2)

• The Percentage of Participants Achieved at Least 2-grade Improvement

  The Investigator's Global Assessment (IGA) was recorded on a 5-point scale, 0 (minimum) to 5 (maximum) \[0 = Clear skin with no signs of erythema and no disease related lesions, 1 = Slight redness with few disease related lesions, 2 = Greater than Grade 1; definite redness with scattered, some disease related lesions, 3 = Greater than Grade 2; marked redness, concentrated, many disease related lesions, 4 = Greater than Grade 3; very bright redness, confluent, highly concentrated disease related lesions, 5= Greater than Grade 4; fiery redness, very extensive disease related lesions covering very large area of the face\]. A higher score indicates a more severe, worse outcome.

  Double-blind phase and Open-label phase Weeks 4 and 12

• The Change in Baseline in Investigator's Global Assessment (IGA) by Visit

  The Investigator's Global Assessment (IGA) was recorded on a 5-point scale, 0 (minimum) to 5 (maximum) \[0 = Clear skin with no signs of erythema and no disease related lesions, 1 = Slight redness with few disease related lesions, 2 = Greater than Grade 1; definite redness with scattered, some disease related lesions, 3 = Greater than Grade 2; marked redness, concentrated, many disease related lesions, 4 = Greater than Grade 3; very bright redness, confluent, highly concentrated disease related lesions, 5= Greater than Grade 4; fiery redness, very extensive disease related lesions covering very large area of the face\]. A higher score indicates a more severe, worse outcome. Negative values indicate improvement (0 = no change, -1 = 1-point improvement, -2 = 2-point improvement)

  Double-blind phase and Open-label phase Weeks 4 and 12

Secondary Outcomes (8)

• The Percentage of Subjects With at Least 30% Improvement in the Facial Angiofibromas Severity Index (FASI) Score.

  Double-blind phase Weeks 4 and 12 and Open-label phase Week 12

• Facial Angifibromas Severity Index (FASI) Score

  Baseline, Double blind phase weeks 4 and 12 and Open-label week 12

• The Percentage of Subjects Achieved at Least 2-grade Improvement in Categorical Lesion Counts by Visit

  Double blind phase Weeks 4 and 12 and Open-label phase Week 12

• Change From Baseline in Lesion Counts

  Double blind phase weeks 4 and 12 and open-label phase week 12

• The Percentage of Subjects Achieved at Least 2-grade Improvement in Lesion Elevation.

  Double blind phase weeks 4 and 12 and open-label phase week 12

Study Arms (3)

Sirolimus 0.2%

ACTIVE COMPARATOR

Sirolimus 0.2% ointment applied topically hs x 12 weeks

Drug: Sirolimus 0.2%

Sirolimus 0.4%

ACTIVE COMPARATOR

Sirolimus 0.4% ointment applied topically hs x 12 weeks

Drug: Sirolimus 0.4%

Placebo

PLACEBO COMPARATOR

Placebo ointment applied topically hs x 12 weeks

Drug: Placebo ointment

Interventions

Sirolimus 0.2% DRUG

Ointment for topical administration hs x 12 weeks

Also known as: Rapamune, rapamycin, mTOR inhibitor

Sirolimus 0.2%

Sirolimus 0.4% DRUG

Ointment for topical administration hs x 12 weeks

Also known as: Rapamune, rapamycin, mTOR inhibitor

Sirolimus 0.4%

Placebo ointment DRUG

Placebo ointment comparator for topical administration hs x 12 weeks

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Generally healthy males or non-pregnant females aged 2 to 21 years, inclusive, at the time of screening.
• Diagnosis of TSC with visible facial angiofibromas of at least grade 3 up to grade 5, inclusive, based on the IGA.
• Subjects with 3 or more isolated, measurable lesions of facial angiofibroma, with color grading score ≥2 for each of the 3 lesions.
• 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.
• The subject and/or their parent or guardian must be willing and able to provide written informed consent/assent.
• Willing and able to comply with all trial requirements.
• 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.
• Subjects should be in good general health based on the subject's medical history, physical exam, and impression of the study doctor.

You may not qualify if:

• 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.
• 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.)
• Is currently receiving any form of immunosuppression therapy or has previously experienced significant immune dysfunction.
• Has a history of sensitivity to any component of the investigational product.
• Is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.
• 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.
• Has facial hair (e.g., beard, sideburns, mustache) that could interfere with study assessments.
• Has had laser surgery or cryotherapy to facial angiofibromas within 6 months preceding study entry.
• 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).
• Has participated in another clinical trial or received an investigational product within 3 months prior to screening.

Sponsors & Collaborators

• Aucta Pharmaceuticals, Inc: lead

Study Sites (8)

Translational Genomics Research

Phoenix, Arizona, 85004, United States

Location

Children's Hospital of Los Angeles, Division of Neurology

Los Angeles, California, 90027, United States

Location

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

Aurora, Colorado, 80045, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

LeBonheur Children's Hospital

Memphis, Tennessee, 38103, United States

Location

Children's Hospital of Fudan University

Shanghai, 201102, China

Location

Related Publications (5)

• 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.

  PMID: 22934754 BACKGROUND

• 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.

  PMID: 23680945 BACKGROUND

• 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.

  PMID: 21692771 BACKGROUND

• 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.

  PMID: 23909960 BACKGROUND

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

  BACKGROUND

MeSH Terms

Conditions

Tuberous Sclerosis; Exanthema; Fibroma; Facies; Erythema

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Marie Tan
• Organization: Aucta Pharmaceuticals, Inc.

Marie.Tan@auctapharma.com

7329129575

Study Officials

• Shoufeng Li, Ph.D

  Aucta Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomly assigned in a 1:1:1 ratio to receive 1 of 2 treatments or placebo. The randomization is stratified by site. Subjects who complete the double-blind phase of the study with an overall compliance rate \>80% and \<120%, as determined by weight of returned study medication, will be offered entry into an open-label period for an additional 12 weeks.

Study Record Dates

• First Submitted: December 1, 2017
• First Posted: December 6, 2017
• Study Start: April 12, 2017
• Primary Completion: March 24, 2023
• Study Completion: March 24, 2023
• Last Updated: December 1, 2025
• Results First Posted: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1); US (7)