Palomid 529 in Patients With Neovascular Age-Related Macular Degeneration
- Wet age-related macular degeneration (AMD) occurs when abnormal blood vessels grow in the back of the eye, and leak blood and other fluids that damage the eye, produce scarring, and lead to blindness. People diagnosed with wet AMD have increased production of a body chemical called vascular endothelial growth factor (VEGF). VEGF is important in the formation of blood vessels in the body, and decreasing the production of VEGF is believed to help wet AMD patients by preventing or slowing the growth of the abnormal blood vessels. Anti-VEGF drugs have been used to decrease the production of VEGF, but some people do not respond completely to these drugs.
- A protein in the body called mTOR also plays a critical role in regulating how cells divide and grow and obtain their blood supply. The experimental chemical Palomid 529 inhibits the production of mTOR. Researchers are interested in determining whether Palomid 529 is safe and can help individuals with wet AMD who have not completely responded to anti-VEGF treatments.
- To evaluate the safety and effectiveness of Palomid 529 as a treatment for wet age-related macular degeneration in individuals who have not responded to standard anti-VEGF treatments.
- Individuals with wet age-related macular degeneration in at least one eye that has not responded to standard anti-VEGF treatments.
- Prior to the first visit, participants should have been seen at the National Eye Institute clinic under a screening or teaching protocol, or NIH protocol 08-EI-0103, High Speed Indocyanine Green Angiography Findings in Induction Regimen of Intravitreal Ranibizumab Injection for Neovascular Age Related Macular Degeneration. One eye will be designated as the study eye to receive the Palomid 529 treatment.
- Participants will have a full physical examination and medical history, a full eye examination to evaluate eye health and vision, angiography to examine the blood vessels in the eyes, and blood and urine tests during the study
- Participants will receive an injection of Palomid 529 into the study eye every 4 weeks during the study, for a total of three injections. Participants may also receive anti-VEGF injections such as ranibizumab (Lucentis ) or bevacizumab (Avastin ) in the study eye 12 days before and 12 days after the Palomid 529 injection.
- Participants may have standard-of-care treatments for the non-study eye if it has wet AMD as well, but may not receive experimental treatments in the non-study eye while they are in this study.
- Participants will return for long-term follow-up examinations as directed by the study researchers.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Unmasked Study to Investigate the Safety and Tolerability of Subconjunctival Injections of Palomid 529 in Patients With Neovascular Age-Related Macular Degeneration|
- The primary outcome is to determine the safety of subconjunctival Palomid 539 neovascular AMD. Safety outcomes include the number and severity of ocular and systemic adverse events.
- Efficacy outcomes include changes in BCVA, fluid status, central retinal thickness, retinal volume, leakage patterns, CNV patterns and fundus appearance. Collecting Complement Factor H Genotypes and pharmacokinetic samples.
|Study Start Date:||December 2010|
|Study Completion Date:||September 2012|
|Primary Completion Date:||September 2012 (Final data collection date for primary outcome measure)|
Drug: Palomid 529
Paloma Pharmaceuticals, Inc. has developed a non-steroidal, wholly synthetic, small molecule drug for application to diseases of aberrant neovasculature, known as Palomid 529.1 Palomid 529 exerts broad activity as an anti-angiogenic agent by inhibiting the mammalian target of rapamycin (Akt/mTor) signal transduction pathway via dissociation of both target of rapamycin complexes (TORC1 and TORC2) in the immune system.
The objective of this study is to evaluate the safety and tolerability of Palomid 529 when administered as subconjunctival injections in participants with choroidal neovascularization (CNV) secondary to neovascular age-related macular degeneration (AMD).
This study will enroll participants with neovascular AMD who have not responded to conventional anti-VEGF treatments. Five participants will be initially accrued; however, up to seven participants who meet the eligibility criteria may be enrolled.
This is a 12-week, unmasked, non-randomized study of three serial 1.9 mg subconjunctival doses of Palomid 529 in neovascular AMD participants who have not responded to conventional anti-VEGF treatments.
The primary outcome is to determine the safety of subconjunctival Palomid 529 for neovascular AMD. Safety outcomes include the number and severity of ocular and systemic adverse events. Secondary efficacy outcomes include changes in best-corrected visual acuity (BCVA), changes in fluid status, central retinal thickness and retinal volume as measured by optical coherence tomography (OCT), changes in leakage patterns as observed on fluorescein angiography (FA), changes in CNV patterns as observed on indocyanine green angiography (ICG), changes in autofluorescence patterns as observed on fundus autofluorescence (FAF) imaging, and changes in fundus appearance as observed on color fundus photography. Additionally, Complement Factor H polymorphisms will be compared with treatment response and pharmacokinetic samples will be collected.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Catherine Meyerle, M.D.||National Eye Institute (NEI)|