Dose-Ranging Efficacy and Safety Study of Topical Rapamycin Cream for Facial Angiofibroma Associated With Tuberous Sclerosis Complex

NCT03826628 | Completed Phase 2 Results FDA Drug

• 1 other identifier: DSLP-01
• Study Type: interventional
• Target: 107
• Locations: 9 countries
• Sites: 17

Brief Summary

The study aims to compare the safety and efficacy of two different strengths of Rapamycin cream, topical and placebo over 26 weeks in the treatment of facial angiofibroma (FA) associated with Tuberous Sclerosis Complex (TSC).

Conditions

Facial Angiofibroma; Tuberous Sclerosis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Obtaining Successful Treatment

  Success on the Investigator Global Assessment (IGA) scale is defined as clear or almost clear with an improvement of at least two grades from baseline. IGA scores range from 0-4: 0=Clear 1. Almost Clear 2. Mild 3. Moderate 4. Severe

  After 26 weeks treatment

Secondary Outcomes (6)

• Time to Treatment Success

  From first dose to 26 weeks (± 2 weeks)

• Change From Baseline in Investigator's Global Assessment

  At baseline and after 26 weeks treatment

• Change From Baseline in Facial Angiofibroma Severity Index (FASI)

  At baseline and after 26 weeks treatment

• Subjective (Participant or Parent/Caregiver) Percentage Change Rating Scale

  After 26 weeks treatment

• Objective (Clinician) Percentage Change Rating Scale

  After 26 weeks treatment

Study Arms (3)

0.5% Rapamycin cream, topical

EXPERIMENTAL

Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks

Drug: rapamycin

1.0% Rapamycin cream, topical

EXPERIMENTAL

Rapamycin cream topical, 0.5% w/w, applied once daily before bed on affected area for 26 weeks

Drug: rapamycin

Placebo

PLACEBO COMPARATOR

Placebo cream topical, applied once daily before bed on affected area for 26 weeks

Drug: placebo

Interventions

rapamycin DRUG

Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks

Also known as: sirolimus

0.5% Rapamycin cream, topical; 1.0% Rapamycin cream, topical

placebo DRUG

Apply to the affected area once a day, approximately half an hour before retiring for bed in the evening, for 26 weeks

Placebo

Eligibility Criteria

• Age: 6 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients aged ≥ 6 years and ≤ 65 years on the day informed consent is obtained
• Patients diagnosed with TSC based on the clinical diagnostic criteria of International Tuberous Sclerosis Complex Consensus Conference 2012 and presenting visible facial angiofibroma
• An FA severity score of 2 or 3 on the IGA scale
• Patients or their legal representatives capable of understanding the explanation of the clinical trial and who give written informed consent for participation
• Patients or their legal representatives able to maintain patient diaries following the instructions of the investigator or sub-investigator

You may not qualify if:

• Patients who cannot carry out the treatment plan or follow-up assessment
• Patients with serious skin lesions such as erosions or ulcers
• Patients with known hypersensitivity to any component of the study product
• Patients who have received rapamycin/sirolimus, everolimus, or temsirolimus within 3 months of enrolment
• Patients who received laser therapy or surgical therapy within 6 months prior to trial enrolment
• Patients who participated in any other clinical trial within 3 months prior to the day of enrolment
• Patients judged unsuitable for this clinical trial by the investigator or sub-investigator
• Pregnant or lactating females
• Sexually active females of childbearing potential not using adequate contraception and sexually active males not using adequate contraception
• Patients with immune dysfunction or receiving any form of immunosuppression
• Patients with severe FA, with a score of 4 on the IGA scale
• Patients with an FA severity score of less than 2 on the IGA scale

Sponsors & Collaborators

• Dermatology Specialties Limited Partnership: lead

Study Sites (17)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

University of California San Diego

La Jolla, California, 92037, United States

Location

All Children's Research Institute

St. Petersburg, Florida, 33701, United States

Location

Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Children's Health Queensland

Brisbane, Queensland, 4101, Australia

Location

Fakultni nemocnice Brno

Brno, 5HG9+4W, Czechia

Location

Bethesda Children's Hospital of the Hungarian Reformed Church

Budapest, G39Q+49, Hungary

Location

University of Pécs

Pécs, H-7624, Hungary

Location

Canterbury District Health Board

Christchurch, Canterbury, 8011, New Zealand

Location

Clinic of Neurology and Psychiatry for Children and Youth

Belgrade, 11000, Serbia

Location

Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Narodný ústav detských chorȏb

Bratislava, 83340, Slovakia

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Clínica Universidad de Navarra

Madrid, 28007, Spain

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Related Publications (1)

• Aitken P, Stanescu I, Boddington L, Mahon C, Fogarasi A, Liao YH, Ivars M, Moreno-Artero E, Trauner D, DeRoos ST, Jancic J, Nikolic M, Balazova P, Price HN, Hadzsiev K, Riney K, Stapleton S, Tollefson MM, Bauer D, Pinkova B, Atkinson H. A novel rapamycin cream formulation improves facial angiofibromas associated with tuberous sclerosis complex: a double-blind randomized placebo-controlled trial. Br J Dermatol. 2023 Oct 25;189(5):520-530. doi: 10.1093/bjd/ljad243.

  PMID: 37463422 RESULT

MeSH Terms

Conditions

Tuberous Sclerosis

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

Covid-19 pandemic halted recruitment, leading to a smaller number of patients recruited than intended (107/120).

Results Point of Contact

• Title: Ioana Stanescu
• Organization: AFT Pharmaceuticals Ltd.

ioana.stanescu@aftpharm.com

+64 9 488 0232

Study Officials

• Ioana Stanescu

  Dermatology Specialties Limited Partnership

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

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

Study Record Dates

• First Submitted: January 29, 2019
• First Posted: February 1, 2019
• Study Start: July 28, 2019
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: September 8, 2023
• Results First Posted: August 14, 2023

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2); US (6); AU (1); SL (1); ES (2); CZ (1); HU (2); TW (1); NZ (1)