AR-14034 for Age-Related Macular Degeneration
(NOVA-1 Trial)
Recruiting in Palo Alto (17 mi)
+5 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Alcon Research
Must be taking: Ocular anti-VEGF
Must not be taking: Ocular anti-VEGF
Disqualifiers: Ocular disease, Glaucoma, Hypertension, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The primary purpose of this study is to evaluate the safety and durability of single- and repeat administration of AR-14034 Sustained Release (SR) in subjects with neovascular age-related macular degeneration (nAMD).
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot have had treatment with an ocular anti-VEGF product within 28 days before the study starts.
What data supports the effectiveness of the drug AR-14034 for age-related macular degeneration?
Research shows that axitinib, a component of AR-14034, effectively inhibits vascular endothelial growth factor (VEGF) receptors, which are involved in the development of abnormal blood vessels in age-related macular degeneration. Studies in animal models and its use in other conditions suggest it may help reduce these abnormal blood vessels.
12345What safety data exists for axitinib, which may be related to AR-14034, in humans?
Axitinib, used for treating certain cancers, has shown variability in how different people process the drug, which can affect safety. Some patients have experienced impaired retinal circulation (reduced blood flow in the eye) as a side effect during treatment.
16789How is the AR-14034 SR implant treatment different from other treatments for age-related macular degeneration?
The AR-14034 SR implant is unique because it delivers axitinib, a drug that blocks specific proteins (VEGF and PDGF) involved in abnormal blood vessel growth, directly into the eye, potentially offering longer-lasting effects compared to standard treatments that require frequent injections.
1241011Eligibility Criteria
This trial is for people with neovascular age-related macular degeneration (nAMD) who have had 3 to 6 prior anti-VEGF treatments in the last 8 months or are newly diagnosed within 9 months. Participants must have a certain level of vision in both eyes and be able to follow study procedures.Inclusion Criteria
Additional requirements may also need to be met as specified in the study guidelines.
Your eye is clear and your pupil can open wide enough for all the tests and procedures in the study.
I have a specific eye condition due to aging that affects my vision.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Stage 1: Dose Escalation
48-week, open-label evaluation of AR-14034 SR with dose escalation in two cohorts
48 weeks
Regular visits through Week 48
Stage 2: Randomized Parallel-Group
56-week double-masked, active comparator evaluation of AR-14034 SR compared with aflibercept
56 weeks
Regular visits through Week 56
Open-label Extension
16-week open-label extension phase for continued treatment
16 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests AR-14034 SR implant at two different doses against Aflibercept Injection and a sham procedure, aiming to assess safety and how long the treatment effects last in controlling nAMD.
5Treatment groups
Experimental Treatment
Active Control
Group I: Cohort 2 (Stage 1)Experimental Treatment2 Interventions
One IVT injection of aflibercept 2 mg at Week -1 and one IVT insertion of AR-14034 SR higher dose at Baseline. Up to one retreatment with AR-14034 SR will be administered between Weeks 4 and 36 according to protocol-specified disease activity criteria.
Group II: Cohort 1 (Stage 1)Experimental Treatment2 Interventions
One intravitreal (IVT) injection of aflibercept 2 mg at Week -1 and one IVT insertion of AR-14034 SR lower dose at Baseline. Up to one retreatment with AR-14034 SR will be administered between Weeks 4 and 36 according to protocol-specified disease activity criteria.
Group III: AR-14034 SR lower dose (Stage 2)Experimental Treatment3 Interventions
One IVT injection of aflibercept 2 mg at Baseline, Week 4, and Week 8, with one IVT insertion of AR-14034 SR lower dose at Week 6. Up to one retreatment of AR-14034 SR will be administered between Weeks 16 and 52 according to protocol-specified disease activity criteria. Sham procedures will be performed between Weeks 16 and 52 except when AR-14034 SR repeat treatment is administered.
Group IV: AR-14034 SR higher dose (Stage 2)Experimental Treatment3 Interventions
One IVT injection of aflibercept 2 mg at Baseline, Week 4, and Week 8, with one IVT insertion of AR-14034 SR higher dose at Week 6. Up to one retreatment of AR-14034 SR will be administered between Weeks 16 and 52 according to protocol-specified disease activity criteria. Sham procedures will be performed between Weeks 16 and 52 except when AR-14034 SR repeat treatment is administered.
Group V: Aflibercept (Stage 2)Active Control2 Interventions
One IVT injection of aflibercept 2 mg at Baseline, Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, and Week 48. Sham procedures will be performed between Weeks 16 and 52.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Northern California Retina Vitreous Associates Medical GroupMountain View, CA
Medical Center Ophthalmology AssociatesSan Antonio, TX
MidAtlantic Retina ResearchPhiladelphia, PA
Retina Vitreous Associates of FloridaSaint Petersburg, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Alcon ResearchLead Sponsor
Aerie PharmaceuticalsLead Sponsor
References
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).
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.
Clinical pharmacology of axitinib. [2021]Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3 that is approved in the US and several other countries for treatment of patients with advanced renal cell carcinoma after failure of one prior systemic therapy. The recommended clinical starting dose of axitinib is 5 mg twice daily, taken with or without food. Dose increase (up to a maximum of 10 mg twice daily) or reduction is permitted based on individual tolerability. Axitinib pharmacokinetics are dose-proportional within 1-20 mg twice daily, which includes the clinical dose range. Axitinib has a short effective plasma half-life (range 2.5-6.1 h), and the plasma accumulation of axitinib is in agreement with what is expected based on the plasma half-life of the drug. Axitinib is absorbed relatively rapidly, reaching maximum observed plasma concentrations (C max) within 4 h of oral administration. The mean absolute bioavailability of axitinib is 58 %. Axitinib is highly (>99 %) bound to human plasma proteins with preferential binding to albumin and moderate binding to α1-acid glycoprotein. In patients with advanced renal cell carcinoma, at the 5-mg twice-daily dose in the fed state, the geometric mean (% coefficient of variation) C max and area under the plasma concentration-time curve (AUC) from time 0-24 h (AUC24) were 27.8 ng/mL (79 %) and 265 ng·h/mL (77 %), respectively. Axitinib is metabolized primarily in the liver by cytochrome P450 (CYP) 3A4/5 and, to a lesser extent (
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.
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.
Individualized dosing with axitinib: rationale and practical guidance. [2018]Axitinib is a potent, selective, vascular endothelial growth factor receptor inhibitor with demonstrated efficacy as second-line treatment for metastatic renal cell carcinoma. Analyses of axitinib drug exposures have demonstrated high interpatient variability in patients receiving the 5 mg twice-daily (b.i.d.) starting dose. Clinical criteria can be used to assess whether individual patients may benefit further from dose modifications, based on their safety and tolerability data. This review provides practical guidance on the 'flexible dosing' method, to help physicians identify who would benefit from dose escalations, dose reductions or continuation with manageable toxicity at the 5 mg b.i.d. dose. This flexible approach allows patients to achieve the best possible outcomes without compromising safety.
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.
Multicenter, phase II study of axitinib, a selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, in patients with metastatic melanoma. [2020]This multicenter, open-label, phase II study evaluated the safety and clinical activity of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, 2, and 3, in patients with metastatic melanoma.
Population pharmacokinetic analysis of axitinib in healthy volunteers. [2022]Axitinib is a potent and selective second generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3 approved for second line treatment of advanced renal cell carcinoma. The objectives of this analysis were to assess plasma pharmacokinetics and identify covariates that may explain variability in axitinib disposition following single dose administration in healthy volunteers.
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.
Combined VEGF and PDGF inhibition for neovascular AMD: anti-angiogenic properties of axitinib on human endothelial cells and pericytes in vitro. [2021]Drugs currently approved for neovascular age-related macular degeneration (nAMD) offer anti-VEGF monotherapy only. Platelet-derived growth factor (PDGF) signaling is pivotal to pericyte-induced stabilization of choroidal neovascularizations (CNV), and causes partial anti-VEGF resistance. No combination therapy for VEGF and PDGF has been approved yet. Axitinib is a tyrosine kinase inhibitor interfering with VEGF and PDGF signaling, and has been approved for the treatment of renal cell carcinoma. This study evaluates anti-angiogenic properties of axitinib in an in-vitro model of choroidal neovascularizations in nAMD.