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

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ClinicalTrials.gov Identifier: NCT03363763
Recruitment Status : Recruiting
First Posted : December 6, 2017
Last Update Posted : August 3, 2018
Sponsor:
Information provided by (Responsible Party):
Aucta Pharmaceuticals, Inc

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).

Condition or disease Intervention/treatment Phase
Angiofibroma of Face Tuberous Sclerosis Drug: Sirolimus 0.2% Drug: Sirolimus 0.4% Drug: Placebo ointment Phase 2

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. The investigational product is sirolimus (0.2% and 0.4%), administered as an ointment formulation for topical administration during the double-blind treatment period. Subjects entering the open-label treatment period will receive sirolimus 0.2% administered as an ointment formulation for topical administration.

Study subjects will be enrolled at 3-5 investigational sites in the United States (US). Approximately 45 subjects who meet the study entry criteria will randomly assigned in a 1:1:1 ratio to receive 1 of 3 treatments. 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 doubleblind phase of the study, with an overall compliance rate >80%, as determined by the number of dose days divided by the total of days between visits, will be offered entry into an open-label period for an additional 12 weeks.The maximum study duration for each subject will be approximately 32 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 4 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : April 12, 2017
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : January 2019


Arm Intervention/treatment
Active Comparator: Arm 1
Sirolimus 0.2% ointment applied topically hs x 12 weeks
Drug: Sirolimus 0.2%
Ointment for topical administration hs x 12 weeks
Other Names:
  • Rapamune
  • rapamycin
  • mTOR inhibitor

Active Comparator: Arm 2
Sirolimus 0.4% ointment applied topically hs x 12 weeks
Drug: Sirolimus 0.4%
Ointment for topical administration hs x 12 weeks
Other Names:
  • Rapamune
  • rapamycin
  • mTOR inhibitor

Placebo Comparator: Arm 3
Placebo ointment applied topically hs x 12 weeks
Drug: Placebo ointment
Placebo ointment comparator for topical administration hs x 12 weeks
Other Name: Placebo




Primary Outcome Measures :
  1. The proportion of subjects with a clinical response of treatment success. [ Time Frame: Week 12 ]
    At least a 2-grade improvement on the Week 12 Investigator Global Assessment (IGA) of the facial skin lesions; or IGA score of clear or almost clear with at least a 2-grade improvement on the Week 12 IGA of the facial skin lesions.


Secondary Outcome Measures :
  1. The proportion of subjects with at least 30% improvement at Week 12 as compared to Baseline in the Facial Angiofibromas Severity Index (FASI) score. [ Time Frame: Week 12 ]
    Based on lesion erythema, size, and extension

  2. The time to reach at least 30% improvement from Baseline in the Facial Angiofibromas Severity Index (FASI) score [ Time Frame: Week 12 ]
    Based on lesion erythema, size, and extension

  3. The proportion of subjects with at least 2-grade improvement as compared to Baseline in categorical lesion counts [ Time Frame: Week 12 ]
    Based on number of lesions

  4. The proportion of subjects with at least 2-grade improvement as compared to Baseline in lesion elevation score [ Time Frame: Week 12 ]
    Based on elevation over normal skin

  5. The proportion of subjects with at least 2-grade improvement as compared to Baseline in the subject self-assessment survey [ Time Frame: Week 12 ]
    Based on redness and disease-related lesions



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Generally healthy males or non-pregnant females aged 2 to 18 years, inclusive, at the time of screening.
  2. Diagnosis of TSC with visible facial angiofibromas of at least grade 2 but not greater than grade 4, inclusive, based on the IGA.
  3. Females of childbearing potential must have a negative urine pregnancy test 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.
  4. The subject and/or their parent or guardian must be willing and able to provide written informed consent/assent.
  5. Willing and able to comply with all trial requirements.
  6. Subject or parent/guardian must be able to complete the subject self-assessment survey in English.
  7. Subjects should be in good general health based on the subject's medical history, physical exam, and impression of the study doctor.

    Exclusion Criteria:

  8. Has severe facial angiofibromas of Grade 5 based on the IGA assessment.
  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 of an mTOR inhibitor (sirolimus, temsirolimus, or everolimus) or other dermatologic treatment to facial angiofibromas within 4 weeks of Baseline.
  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, 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03363763


Contacts
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Contact: Clinical Project Manager 678-373-4660 ext 112 Mary.Leone@peachtreebrs.com
Contact: Xiaoyang Tang, M.S. 732-640-0030 xiaoyang.tang@auctapharma.comm

Locations
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United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Grace Bazin, BSN, BS    617-355-5230    Grace.Bazin@childrens.harvard.edu   
Contact: Lindsay Swanson, MS    617-355-5111    Lindsay.Swanson@childrens.harvard.edu   
Principal Investigator: Marilyn G. Liang, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Lorraine Greer, MSM    267-426-7032    greerl@email.chop.edu   
Principal Investigator: Albert C. YAN, MD         
Sub-Investigator: Katherine Taub, MD         
United States, Tennessee
LeBonheur Children's Hospital Recruiting
Memphis, Tennessee, United States, 38103
Contact: Tracee Ridley- Pryor    901-287-5388    Tracee.Ridley-Pryor@lebonheur.org   
Contact: Margaret Bissler    901-287-7467    margaret.bissler@lebonheur.org   
Principal Investigator: James W. Wheless, MD         
Sub-Investigator: Teresa Wright, MD         
Sponsors and Collaborators
Aucta Pharmaceuticals, Inc
Investigators
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Study Director: Shoufeng Li, Ph.D Aucta Pharmaceuticals, Inc

Publications:
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Responsible Party: Aucta Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT03363763     History of Changes
Other Study ID Numbers: AUCTA-UAP006-PH2
First Posted: December 6, 2017    Key Record Dates
Last Update Posted: August 3, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Aucta Pharmaceuticals, Inc:
rash
fibroma
skin
facial
face
bumps
redness
erythema
lesions
papules
blood vessel
cheeks

Additional relevant MeSH terms:
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Sclerosis
Tuberous Sclerosis
Angiofibroma
Pathologic Processes
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
Genetic Diseases, Inborn
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs