Intravitreal Injections of Sirolimus in the Treatment of Central Geographic Atrophy
This study will seek to enroll 50 persons who have central geographic atrophy associated with AMD who have also shown progressive worsening (growth) over time. Eligible participants will be randomly chosen to receive one of the following treatments in the study eye:
- A 20 μL (440 μg) IVT injection of sirolimus, or
- 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 (about 2 weeks following screening/enrollment visit) and every month thereafter. The visit schedule is as follows:
- A clinical evaluation, including safety measures, will occur monthly.
- Vision will be measured at the screening/enrollment visit and at 2, 3, 6, 12, 18 and 24 months after the first injection has occurred.
- Fundus autofluorescence will occur at screening/enrollment and at 2, 6, 12, 18 and 24 months after the first injection has occurred.
- 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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
|Official Title:||Multi-Center, Randomized, Single Masked Phase 2 Study of Intravitreal Injections of Sirolimus in the Treatment of Central Geographic Atrophy Associated With Age-Related Macular Degeneration|
- Rate of change in area of geographic atrophy [ Time Frame: Every 6 months after enrollment for 2 years ] [ Designated as safety issue: No ]
- Change in best-corrected visual acuity [ Time Frame: Every 6 months after enrollment for 2 years ] [ Designated as safety issue: No ]
- Number and severity of systemic and ocular toxicities, adverse events and infections [ Time Frame: Monthly for 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2012|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Monthly 20 μL (440 μg) intravitreal injection of 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.
Other Name: Rapamycin, Rapamune
Sham Comparator: Lidocaine
Monthly subconjunctival injection of 2% lidocaine
|United States, Maryland|
|Elman Retina Group|
|Baltimore, Maryland, United States, 21237|
|Study Chair:||Emily Y Chew, MD||National Eye Institute (NEI)|