AR-14034 for Age-Related Macular Degeneration (NOVA-1 Trial)
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Alcon Research
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).
Do I have to stop taking my current medications for the trial?The protocol does not specify if you need to stop taking your current medications. However, you cannot have had ocular anti-VEGF treatment within 28 days before the trial starts.
Is the AR-14034 SR implant a promising treatment for Age-Related Macular Degeneration?Yes, the AR-14034 SR implant, which uses axitinib, shows promise as a treatment for Age-Related Macular Degeneration. It targets and blocks specific proteins that help form unwanted blood vessels in the eye, which are a problem in this condition. This approach could offer benefits over current treatments, which often require frequent eye injections.3671011
What safety data is available for AR-14034 in treating age-related macular degeneration?The safety data for AR-14034, which includes axitinib, primarily comes from studies on its use in other conditions like metastatic renal cell carcinoma and melanoma. Axitinib has shown high interpatient variability in drug exposure and has been associated with adverse events such as impaired retinal circulation. Safety and tolerability data have been used to guide individualized dosing to manage toxicity. However, specific safety data for AR-14034 in age-related macular degeneration is not directly available from the provided research.23589
What data supports the idea that AR-14034 for Age-Related Macular Degeneration is an effective treatment?The available research shows that axitinib, which is part of AR-14034, has been studied for its effects on age-related macular degeneration in animal models. One study found that axitinib, when delivered in a specific way, could potentially offer more benefits than the current standard treatments. However, the research primarily focuses on animal models and other conditions, like advanced renal cell carcinoma, rather than directly on age-related macular degeneration in humans. Therefore, while there is some promise, more direct evidence in humans is needed to fully support its effectiveness for this condition.1341011
Eligibility 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
I have a specific eye condition due to aging that affects my vision.
I've had 3-6 eye injections for VEGF in the last 8 months and they worked.
Treatment Details
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
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.
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.
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).
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 (
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.
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.
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.
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.
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.