Topical Rapamycin to Erase Angiofibromas in TSC

NCT01526356 | Completed Phase 2 Results DMC

• 2 other identifiers: HSC-MS-11-0501Department of Defense USAMRMC
• Study Type: interventional
• Target: 179
• Locations: 2 countries
• Sites: 10

Brief Summary

The study is a multi-center prospective, randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of a topically applied formulation of rapamycin to cutaneous angiofibromas in subjects with Tuberous Sclerosis Complex (TSC). Subjects will apply either the topical vehicle containing rapamycin or the topical vehicle alone nightly to their angiofibromas for six months. The primary goal of this study is to evaluate the efficacy of the topical medication for reduction of cutaneous angiofibromas in patients with TSC. The secondary goal of this study is to confirm the safety of the topical medication.

Conditions

Angiofibromas; Tuberous Sclerosis

Keywords

Angiofibroma; Tuberous Sclerosis; Rapamycin; Sirolimus; mTOR

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Facial Angiofibroma Grading Scale (AGS) Score

  Subject's lesion/s will be digitally photographed before initial application (visit 1), at each study visit (visits 2 through 6), and immediately prior to study termination (visit 7). Following completion of the study, all photographs will be evaluated by two independent dermatologists blinded to both the treatment arm and the stage of treatment. The dermatologists will assess each photograph's appearance using the facial Angiofibroma Grading Scale (AGS), which assesses the forehead, nose, cheeks, and chin for erythema, average lesion size, lesion density, and percent involvement, as well as presence of any pedunculated angiofibromas. A total score is reported with a range of 0 to 202, with higher scores representing a worse outcome.

  baseline, 6 months

Secondary Outcomes (4)

• Photo Readers' Rating (Better, Same, or Worse) of Paired Baseline and End-of-trial (EOT) Photographs for Each Patient

  baseline, 6 months

• Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Dermatology Life Quality Index (DLQI)

  baseline, 6 months

• Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Children's Dermatology Life Quality Index (CDLQI)

  baseline, 6 months

• Change in Quality of Life (QOL) Questionnaire Scores as Assessed by the Family Dermatology Life Quality Index (FDLQI)

  baseline, 6 months

Other Outcomes (2)

• Number of Events of Dermatologic Sensitivity at the Site of Application

  6 months

• Number of Participants With Systemic Uptake of Topically Applied Rapamycin

  6 months

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Cream only

Drug: Placebo

0.1 % Rapamycin

ACTIVE COMPARATOR

0.1% Rapamycin cream

Drug: Rapamycin

1% Rapamycin

ACTIVE COMPARATOR

1% Rapamycin cream

Drug: Rapamycin

Interventions

Placebo DRUG

Study cream is applied nightly to the affected areas on the face.

Also known as: Rapamycin

Placebo

Rapamycin DRUG

Study cream is applied nightly to the affected areas on the face. Low Dose

0.1 % Rapamycin

Eligibility Criteria

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

You may qualify if:

• Subjects must be willing and able to comply with all trial requirements.
• Subject has a diagnosis of TSC and has visible facial angiofibromas.
• Female subjects of child bearing potential must not be pregnant and must agree to use appropriate contraceptive methods .

You may not qualify if:

• Subject is currently receiving therapy with Rapamycin.
• Subject is receiving any form of immunosuppression or has previously experienced immune dysfunction.
• Subject is currently participating in or has participated within the last 30 days in a clinical trial involving an investigational drug.
• Subject has a known hypersensitivity to either the vehicle or Rapamycin.
• Subject is a pregnant or nursing female.
• Subject has other dermatologic conditions that would preclude or prevent adequate assessment of changes to their facial angiofibromas.
• Subject has had laser surgery, cryotherapy, or other dermatologic treatment to their facial angiofibromas within the previous 6 months.

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (10)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

UCLA Mattel Children's Hospital

Los Angeles, California, 90095, United States

Location

Jack & Julia Center for TSC at Oakland Children's Hospital & Research Center

Oakland, California, 94609, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

Herscot Center for Adults and Children with TSC Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Clinic Without Walls

Saint Paul, Minnesota, 55102-2697, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Texas Scottish Rite Hospital

Dallas, Texas, 75219, United States

Location

The University of Texas Medical School at Houston

Houston, Texas, 77030, United States

Location

Sydney Children's Hospital

Sydney, New South Wales, Australia

Location

Related Publications (1)

• Koenig MK, Bell CS, Hebert AA, Roberson J, Samuels JA, Slopis JM, Tate P, Northrup H; TREATMENT Trial Collaborators. Efficacy and Safety of Topical Rapamycin in Patients With Facial Angiofibromas Secondary to Tuberous Sclerosis Complex: The TREATMENT Randomized Clinical Trial. JAMA Dermatol. 2018 Jul 1;154(7):773-780. doi: 10.1001/jamadermatol.2018.0464.

  PMID: 29800048 DERIVED

MeSH Terms

Conditions

Angiofibroma; Tuberous Sclerosis

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms; Hamartoma; 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

Results Point of Contact

• Title: Mary Kay Koenig, MD
• Organization: The University of Texas Health Science Center at Houston

mary.k.koenig@uth.tmc.edu

713-500-7142

Study Officials

• Mary Kay Koenig, MD

  The University of Texas Medical School at Houston

  PRINCIPAL INVESTIGATOR

• Hope Northrup, MD

  The University of Texas Medical School at Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: 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: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 1, 2012
• First Posted: February 3, 2012
• Study Start: May 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: October 26, 2020
• Results First Posted: October 26, 2020

Record last verified: 2020-09

Locations

US (9); AU (1)