Axitinib Implant for Age-Related Macular Degeneration
Recruiting in Palo Alto (17 mi)
+57 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Ocular Therapeutix, Inc.
Must be taking: Aflibercept
Disqualifiers: Monocular, Scar, Fibrosis, Atrophy, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?Study to Evaluate the Efficacy and Safety of Intravitreal OTX-TKI (Axitinib Implant) in Subjects with Neovascular Age- Related Macular Degeneration
Do I need to stop my current medications for this trial?
The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.
Is the Axitinib Implant safe for humans?
Axitinib has been used in humans for other conditions, but there was a case where it caused impaired blood flow in the eye during treatment for kidney cancer. In lab tests, a formulation of axitinib showed low toxicity to human eye cells, suggesting it might be safe, but more research is needed to confirm this for the implant.
12345How is the Axitinib Implant drug different from other treatments for age-related macular degeneration?
The Axitinib Implant is unique because it delivers axitinib, a drug that blocks both VEGF and PDGF pathways, directly to the eye, potentially offering longer-lasting effects and reducing the need for frequent injections compared to standard anti-VEGF treatments.
14678Eligibility Criteria
This trial is for individuals who have been diagnosed with Neovascular Age-Related Macular Degeneration (nAMD) within the last 3 months. They should have received up to two aflibercept injections recently and must not have significant scarring or vision loss in their other eye.Inclusion Criteria
I was diagnosed with nAMD within the last 3 months and have had up to 2 aflibercept injections.
Have provided written consent
I have not received any treatment for my wet AMD affecting the center of my vision.
Exclusion Criteria
Monocular subject or Best Corrected Visual Acuity (BCVA) score of less than 20 ETDRS letters or 20/400 in fellow eye at Screening
Evidence of a scar, fibrosis, or atrophy of more than 50% of the total lesion in the study eye.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either the OTX-TKI (Axitinib Implant) or Aflibercept for neovascular age-related macular degeneration
48 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests the effectiveness and safety of an Axitinib implant (OTX-TKI) compared to standard treatment with aflibercept injections in patients suffering from nAMD.
3Treatment groups
Experimental Treatment
Active Control
Group I: OTX-TKI Re-doseExperimental Treatment1 Intervention
Group II: Aflibercept 8mg high doseExperimental Treatment1 Intervention
Group III: Aflibercept 2mg on labelActive Control1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Retina Vitreous Associates of Florida- Saint PetersburgSaint Petersburg, FL
The Retina Center Of New Jersey, LLC - BloomfieldBloomfield, NJ
Cumberland Valley Retina ConsultantsHagerstown, MD
Sierra Eye AssociatesReno, NV
More Trial Locations
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Who Is Running the Clinical Trial?
Ocular Therapeutix, Inc.Lead Sponsor
FortreaIndustry Sponsor
Duke UniversityCollaborator
References
Oral Tyrosine Kinase Inhibitor for Neovascular Age-Related Macular Degeneration: A Phase 1 Dose-Escalation Study. [2019]An oral treatment for neovascular age-related macular degeneration would be less burdensome than repeated intravitreous injections. X-82 is an oral tyrosine kinase inhibitor active against vascular endothelial growth factor (VEGF) and platelet-derived growth factor.
Intravitreal pegaptanib sodium for choroidal neovascularisation secondary to age-related macular degeneration: Pan-European experience. [2016]To evaluate visual outcomes in patients with neovascular age-related macular degeneration (NV-AMD) who were treated with pegaptanib sodium in European clinical ophthalmology practices.
Impaired Retinal Circulation during Axitinib Treatment for Metastatic Renal Cell Carcinoma. [2022]Axitinib, an orally administered vascular endothelial growth factor receptors 1, 2, and 3 inhibitor, is widely used as the second-line treatment for metastatic renal cell carcinoma. We present a case of metastatic renal cell carcinoma who developed a novel ocular adverse event, impaired retinal circulation, during axitinib therapy.
Antiangiogenic effects of axitinib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, on laser-induced choroidal neovascularization in mice. [2018]To investigate the effects of axitinib, an inhibitor of vascular endothelial growth factor receptors, on choroidal neovascularization (CNV) in an animal model of neovascular age-related macular degeneration (AMD).
Axitinib-Loaded Poly(Lactic-Co-Glycolic Acid) Nanoparticles for Age-Related Macular Degeneration: Formulation Development and In Vitro Characterization. [2020]Despite all the research aiming to treat ocular diseases, age-related macular degeneration (AMD) remains one of the serious diseases worldwide, which needs to be treated. Neovascularization is a key factor in AMD and thus antiangiogenic therapy is beneficial in reducing the development of new abnormal blood vessels. Axitinib, multireceptor tyrosine kinase inhibitor, is a small molecule that works by blocking vascular endothelial growth factor receptors (VEGFR) and platelet-derived growth factor receptors (PDGFR) responsible for developing neovascularization. The goal of this study is to develop a sustained release formulation of axitinib-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles to minimize frequent administration of the drug by intravitreal injection. The nanoparticles were characterized for particle size and zeta potential, as well as using differential scanning calorimetry, transmission electrode microscope, and in vitro drug release profile. The cytotoxicity of the formulation was evaluated on human retinal pigmented epithelium ARPE19 cells by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide salt] assay. The cellular uptake, antimigration assay, and vascular endothelial growth factor (VEGF) expression levels were found out in vitro using cells. The optimized formulation was 131.33 ± 31.20 nm in size with -4.63 ± 0.76 mV zeta potential. Entrapment efficiency was found to be 87.9% ± 2.7%. The cytotoxicity of ARPE19 cells was <12% for nanoparticles suggesting the in vitro compatibility at 10 μM concentration of drug. Cellular uptake, antimigration assay, and VEGF expression levels for the nanoparticles suggested greater uptake, significant antiangiogenic potential, and inhibition of VEGF activity. The results showed successful development of axitinib-loaded PLGA nanoparticles as an alternative potential treatment for AMD.
Axitinib inhibits retinal and choroidal neovascularization in in vitro and in vivo models. [2018]Age-related Macular Degeneration (AMD) is the leading cause of visual impairment and blindness in the elderly in developed countries. Neovascular/exudative (wet) AMD is the aggressive form of AMD and can involve choroidal neovascularization and vascular leakage. Anti-vascular endothelial growth factor (anti-VEGF) medications have significantly improved treatment of wet-AMD. However, only approximately 40% of patients obtain full benefit from anti-VEGF therapy and the medications are given by intravitreal injection. Axitinib, a small molecule multi-receptor tyrosine kinase inhibitor used for the treatment of advanced renal cell carcinoma, is taken orally and inhibits VEGF activity by blocking VEGF receptors. Axitinib also has the advantage of blocking platelet derived growth factor (PDGF) receptors which play a role in neovascularization. Using in vitro human retinal microvascular endothelial cells (HRMVECs), human brain vascular pericytes (HBVRs), 3D co-culture vessel sprout assay, and in vivo laser induced rat choroidal neovascularization (CNV) models, the effect of axitinib on neovascularization was evaluated. Axitinib inhibited neovascularization better than anti-VEGF and/or anti-hPDGF-B mAb in the in vitro models demonstrating that combined inhibition of both VEGF and PDGF pathways may be synergistic in treating wet-AMD. Additionally, axitinib showed good efficacy at a low dose (0.875 mg/day) in laser-induced CNV model in rats. In conclusion our data shows that axitinib, an inhibitor of VEGF and PDGF-B pathways may be useful in ameliorating wet-AMD therapy.
Evaluation of Long-Lasting Potential of Suprachoroidal Axitinib Suspension Via Ocular and Systemic Disposition in Rabbits. [2021]Axitinib, a tyrosine kinase inhibitor, is a potent inhibitor of vascular endothelial growth factor (VEGF) receptors -1, -2 and -3. Suprachoroidal (SC) delivery of axitinib, combined with pan-VEGF inhibition activity of axitinib, has the potential to provide additional benefits compared to the current standard of care with intravitreal anti-VEGF-A agents. This study evaluated the ocular pharmacokinetics and systemic disposition of axitinib after SC administration in rabbits.
SAFETY AND THERAPEUTIC EFFECTS OF ORALLY ADMINISTERED AKST4290 IN NEWLY DIAGNOSED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION. [2022]To evaluate the safety and therapeutic effects of orally administered AKST4290 (formerly BI 144807 and ALK4290) in treatment-naive patients with neovascular age-related macular degeneration.