Topical Everolimus in Patients With Tuberous Sclerosis Complex

NCT02860494 | Withdrawn Phase 2 DMC

• 2 other identifiers: 69HCL16_00622018-002531-18
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Tuberous sclerosis complex (TSC) is a rare genetic multisystem disorder characterized by the development of hamartomas in several organs (e.g. brain, heart, kidney, liver, lung), and skin in more than 90% of cases. Facial angiofibromas (FA), present in about 80% of patients, are a stigmatizing hallmark of the disease. Everolimus could be a candidate for use as a topical formulation to treat FA. This adaptive seamless Phase II/III study primary objective is to determine the dose of topical everolimus for treatment of FA and evaluate the efficacy and safety of topical everolimus versus placebo in patients with angiofibromas.

Conditions

Facial Angiofibromas

Keywords

Tuberous sclerosis complex (TSC); topical everolimus; seamless design; dose-escalation study; m-TOR inhibitor

Outcome Measures

Primary Outcomes (1)

• Facial Angiofibroma Severity Index (FASI)

  The FASI is a composite score summing the scores for erythema (0-3), size (0-3) and extension of FA (2:\<50% of the cheek surface; 3:\>50% of the cheek surface). The FASI will be centrally-measured on patient's face photographs by an independent and blinded adjudication committee of 2 dermatologists, with third-dermatologist review for disagreements.

  6 months

Secondary Outcomes (8)

• FA size

  6 months

• Dermatologist's global assessment of efficacy

  6 months

• Patient or parents self-assessment

  6 months

• Local tolerance of the topically applied formulation using patient self-assessment

  6 months

• blood levels of topically applied everolimus

  6 months

Study Arms (4)

Topical everolimus 0.1%

EXPERIMENTAL

Everolimus topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months. Dose regimens will be identical, regardless of the dose-strength of the topical formulation. The topical formulation will be applied onto areas of the face affected by FA by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.).

Drug: Everolimus

Topical everolimus 0.5%

EXPERIMENTAL

Everolimus topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months. Dose regimens will be identical, regardless of the dose-strength of the topical formulation. The topical formulation will be applied onto areas of the face affected by FA by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.).

Drug: Everolimus

Topical everolimus 1%

EXPERIMENTAL

Everolimus topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months. Dose regimens will be identical, regardless of the dose-strength of the topical formulation. The topical formulation will be applied onto areas of the face affected by FA by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.).

Drug: Everolimus

Topical placebo

PLACEBO COMPARATOR

Topical placebo will be identical to the everolimus topical formulation. Topical placebo will be applied to the affected areas, once daily, in the evening, for 6 months by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.).

Drug: Placebo

Interventions

Everolimus DRUG

Everolimus topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months. Dose regimens will be identical, regardless of the dose-strength of the topical formulation. The topical formulation will be applied onto areas of the face affected by FA by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.).

Topical everolimus 0.1%; Topical everolimus 0.5%; Topical everolimus 1%

Placebo DRUG

Placebo topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months, by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.).

Topical placebo

Eligibility Criteria

• Age: 0 Years - 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients over the age of 2 years
• With definite or possible diagnosis of TSC
• With at least 3 FA, diagnosed by a dermatologist
• Patients (or parents or legal guardians) who have provided written informed consent prior to participation in the study
• Willing and able to comply with study requirements
• With negative blood pregnancy test at the screening visit and using effective contraceptive methods for women of childbearing potential, up to 12 weeks after treatment discontinuation
• Covered by national health insurance

You may not qualify if:

• Systemic treatment by sirolimus, everolimus, or any other immunosuppressive drug, during the previous 6 months
• Use of topical tacrolimus or sirolimus on the face, during the previous 6 months
• Destructive treatment (laser therapy, surgery, cryotherapy) of facial angiofibromas during the previous 6 months
• Concomitant use of topical treatments that could affect facial erythema (e.g. Brimonidine)
• Known internal organ involvement requiring systemic mTOR inhibitor in the next 6 months
• Immunosuppression (immunosuppressive disease or immunosuppressive treatment)
• Known chronic infectious disease Known hypersensitivity to mTOR inhibitor
• Neutropenia \< 1000/mm3
• Thrombopenia \< 75,000/mm3
• Chronic renal insufficiency (estimated Glomerular Filtration Rate \< 60 mls/min)
• Chronic liver disease (SGOT or SGPT \> 3 times upper normal limit)
• Uncontrolled dyslipidaemia
• Uncontrolled diabetes
• Brest feeding or pregnant women, or women on childbearing age without any effective method of contraception during treatment and up to 12 weeks after treatment discontinuation
• Subjects who, in the Investigator's opinion, are unable or unwilling to comply with the protocol.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hopital Femme Mère Enfant

Bron, France

Location

MeSH Terms

Conditions

Tuberous Sclerosis

Interventions

Everolimus

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)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Alice PHAN, MD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

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: SPONSOR

Study Record Dates

• First Submitted: August 4, 2016
• First Posted: August 9, 2016
• Study Start: December 1, 2020
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: May 3, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)