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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03363763
Recruitment Status : Recruiting
First Posted : December 6, 2017
Last Update Posted : April 28, 2020
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. 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.

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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 : November 2020
Estimated Study Completion Date : April 2021


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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 3 up to grade 5, inclusive, based on the IGA.
  3. 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) 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 and subject diary in English or another language into which the documents have been officially translated.
  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 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.
  9. . Has received oral therapy or topical therapy of an mTOR inhibitor (sirolimus, temsirolimus, or everolimus) or other dermatologic treatment to facial angiofibromas within 8 weeks of Baseline or other dermatological treatment to facial angiofibormas within 4 weeks of baseline.(Sunscreen is expected to be used in this patient population and is not considered treatment.)
  10. Is currently receiving any form of immunosuppression therapy or has previously experienced significant immune dysfunction.
  11. Has a history of sensitivity to any component of the investigational product.
  12. Is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.
  13. 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.
  14. Has facial hair (e.g., beard, sideburns, mustache) that could interfere with study assessments.
  15. Has had laser surgery or cryotherapy to facial angiofibromas within 6 months preceding study entry.
  16. 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: Cynthia S Sandy, RN, BSN, MS, PMP 770-545-4030 cindy.sandy@peachtreebrs.com
Contact: Wilson Chang 732-640-6030 wilson.chang@auctapharma.com

Locations
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United States, Arizona
Translational Genomics Research Completed
Phoenix, Arizona, United States, 85004
United States, California
Children's Hospital of Los Angeles, Division of Neurology Recruiting
Los Angeles, California, United States, 90027
Contact: Martha Arellano-Garcia    323-361-5812    margarcia@chla.usc.edu   
Principal Investigator: Tena Rosser, MD         
United States, Colorado
Children's Clinical Research Organization, Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Sharolene Goodman    720-777-5379    sharolene.goodman@childrenscolorado.org   
Principal Investigator: Anna Bruckner, MD         
United States, Georgia
Children's Healthcare of Atlanta Completed
Atlanta, Georgia, United States, 30329
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Michelle DeLeo    617-355-5173    Michelle.DeLeo@childrens.harvard.edu   
Contact: Julia Costantini    617-355-1494    Julia.costantini@childrens.harvard.edu   
Principal Investigator: Mustafa Sahin, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Donnette Paris    267-426-7167    PARIS@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: Kenishia Guy    901-287-5958    kinishia.Guy@lebonheur.org   
Contact: Tracee Ridley-Pryor    901-287-5388    Tracee.Ridley-Pryor@lebonheur.org   
Principal Investigator: James W. Wheless, MD         
Sub-Investigator: Teresa Wright, MD         
China
Children's Hospital of Fudan University Not yet recruiting
Shanghai, China, 201102
Contact: Ji Wang       xiaojizi12@sina.com   
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    
Other Study ID Numbers: AUCTA-UAP006-PH2
First Posted: December 6, 2017    Key Record Dates
Last Update Posted: April 28, 2020
Last Verified: April 2020
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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Tuberous Sclerosis
Angiofibroma
Sclerosis
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
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs