NCT01675947

Intravitreal Injections of Sirolimus in the Treatment of Geographic Atrophy

Multi-Center, Randomized, Single Masked Phase 2 Study of Intravitreal Injections of Sirolimus in the Treatment of Geographic Atrophy Associated With Age-Related Macular Degeneration

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 52 (actual)
• Sponsor: National Eye Institute (NEI) · NIH
• Sex: All
• Age: 55 Years
• Healthy volunteers: Not accepted

Summary

This study will seek to enroll 50 persons who have central or non-central geographic atrophy (GA) associated with age-related macular degeneration (AMD). GA in treated eye must be between 0.75 disk areas (DA) and 8 DA. Eligible participants will be randomly chosen to receive one of the following treatments in the study eye: 1. A 20 μL (440 μg) intravitreal (IVT) injection of sirolimus, or 2. A sham treatment (subconjunctival injection of lidocaine) Participants with two (2) eligible eyes will have one eye randomly assigned to receive intravitreal sirolimus and no sham in the fellow eye. The first injection will begin at Day 0, which may occur on the date of screening/enrollment or up to two weeks following screening/enrollment visit, and every month thereafter. The visit schedule is as follows: 1. A clinical evaluation, including safety measures, will occur monthly. 2. Vision will be measured at the screening/enrollment visit and at 2, 3, 6, 9, 12, 18 and 24 months after the first injection has occurred. 3. Fundus autofluorescence will occur at screening/enrollment and at 2, 6, 12, 18 and 24 months after the first injection has occurred. 4. Fundus color photography and optical coherence tomography will occur at screening/enrollment and at 6, 12, 18 and 24 months after the first injection has occurred. The primary goal is to evaluate whether the persons receiving the sirolimus injections show a slower worsening of geographic atrophy compared to the persons receiving the sham injections. A secondary goal is to evaluate the impact of sirolimus on vision compared to the sham. NOTE: As of May 30, 2014, study injections were discontinued due to safety concerns. No further enrollments will occur and follow-up will continue on all active study participants on a quarterly basis. That is, on visits coinciding with 3 month intervals from date of enrollment.

Conditions

• Geographic Atrophy

Interventions

Type	Name	Description
DRUG	Sirolimus	Immunosuppressive agent. Blocks the T-lymphocyte activation and smooth muscle and endothelial cell proliferation that occurs in response to antigenic and cytokine (interleukin IL-2, IL-4 and IL-15) stimulation through either Ca2+-dependent or Ca2+-independent pathways. Sirolimus arrests cell cycle progression by direct interaction with two intracellular proteins (immunophilin FK binding protein 12 (FKBP-12) and the mammalian target of rapamycin (mTOR), a multifunctional serine-threonine kinase). In cells, sirolimus binds to FKBP-12, and the resulting sirolimus-FKBP-12 complex then binds to and inhibits mTOR.
DRUG	Lidocaine	Lidocaine 2%

Timeline

• Start date: 2012-02-01
• Primary completion: 2015-06-01
• Completion: 2016-02-01
• First posted: 2012-08-30
• Last updated: 2015-12-10

Locations

13 sites across 1 country: United States