Sirolimus for Retinal Astrocytic Hamartoma

Intravitreal Injection of Sirolimus in the Treatment of Aggressive Retinal Astrocytic Hamartoma

A single patient study using intravitreal Sirolimus to treat a patient with multiple retinal astrocytic hamartomas (RAH) of both eyes.

Study Overview

• Status: Completed
• Conditions: Retinal Astrocytic Hamartoma
• Intervention / Treatment: Drug: Sirolimus

Detailed Description

Retinal astrocytic hamartomas (RAH) are benign tumors of glial cells arising from astrocytes in the nerve-fiber layer of the retina. They are often associated with tuberous sclerosis complex (TSC) and, more rarely, neurofibromatosis type 1 (NF1). RAH may be caused by dysregulated tumor suppressors genes TSC1 or TSC2, which play a role in cell cycle regulation in retinal astrocytes via the PDGF-signalling pathway. Downregulation of TSC1 or TSC2 can result in hyperactivation of mTOR. Sirolimus is an inhibitor of mTOR, therefore inhibiting cell growth and proliferation of astrocytes. Systemic mTOR inhibitors (sirolimus and everolimus) have shown impressive reduction in the size of RAH in animal models and many human case series.

This single patient study is investigating the use of concurrent oral and intravitreal Sirolimus to treat a patient with multiple retinal astrocytic hamartomas (RAH) of both eyes to improve intraocular response and reduce duration of treatment. The patient has no other clinical features suggestive of neurofibromatosis and a presumed diagnosis of tuberous sclerosis is being considered, with only two hypopigmented skin lesions noted.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 16 years (Child)
• Accepts Healthy Volunteers: No

Description

Single case diagnosed with multiple retinal astrocytic hamartomas (RAH) of both eyes with imminent threat to vision.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intravitreal Sirolimus

Drug: Sirolimus; An intravitreal injection of 20 µL of drug will be given through the pars plana of the eye. The injected eye will be treated with topical antibiotic and steroid eye drops prescribed for 7 to 10 days after the injection. The first injection will only be provided into the worse eye despite both eyes showing signs of exudation. Injection into the other eye will be considered only two months after the safety of this first injection is determined. Safety and efficacy of treatment will be determined by repeat eye examinations in the eye clinic one day, one week and one month after each injection. The interval between injections is roughly suggested to be between 3 to 8 weeks based on the drug deposit present in the eye. A total of 3-12 injections will be given per eye, over 6-24 months.; Other Names: DE-109

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Size of Retinal Astrocytic Hamartomas compared to baseline	Measured by ophthalmic imaging	21 months
Amount of retinal exudate compared to baseline	Measured by ophthalmic imaging	21 months
Retinal detachment progression/regression compared to baseline	Measured by ophthalmic imaging	21 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual acuity compared to baseline	Measured using logMAR virtual activity test	21 months

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2020
• Primary Completion (Actual): March 22, 2024
• Study Completion (Actual): March 22, 2024

Study Registration Dates

• First Submitted: December 16, 2020
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (Actual): January 13, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Hamartoma; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: 1000072947

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No