Axitinib Implant for Age-Related Macular Degeneration

Not currently recruiting at 114 trial locations

Overseen By Nichole Wilkes

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ocular Therapeutix, Inc.

Disqualifiers: Monocular, Scar, Fibrosis, Atrophy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called the axitinib implant to determine its effectiveness for people with neovascular age-related macular degeneration, a condition that causes vision loss. Researchers aim to assess the implant's effectiveness and safety in improving vision. One group will receive the axitinib implant, while another group will not, allowing for a comparison of results. The trial seeks participants who are 50 or older, have not received treatment for this eye condition before, and have good vision in one or both eyes. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

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's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the OTX-TKI (axitinib implant) is generally safe for individuals with neovascular age-related macular degeneration. Previous studies revealed no unexpected safety issues, and patients tolerated the treatment well, with no new problems identified. This suggests that the axitinib implant is safe for humans, according to past research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for age-related macular degeneration?

Unlike the standard treatments for age-related macular degeneration, which often involve repeated eye injections, the axitinib implant offers a new delivery method. This implant slowly releases the medication directly into the eye over time, potentially reducing the need for frequent visits to the doctor for injections. Researchers are excited about axitinib, a potent tyrosine kinase inhibitor, because it targets specific pathways involved in the abnormal blood vessel growth that characterizes this condition. This approach not only aims to improve patient comfort and compliance but also has the potential to enhance treatment efficacy by maintaining consistent drug levels in the eye.

What evidence suggests that the OTX-TKI (axitinib implant) could be an effective treatment for age-related macular degeneration?

Studies have shown that the OTX-TKI (axitinib implant), which participants in this trial may receive, holds promise for treating neovascular age-related macular degeneration (AMD). This implant reduces the need for frequent eye injections to just 1-2 per year while still controlling the disease and helping maintain vision. Initial findings suggest it reduces the need for other treatments by 89%. These treatments usually target a protein called VEGF, which causes harmful blood vessel growth in the eye. The implant releases medication slowly, providing benefits for up to 9 months. Overall, research supports its potential to effectively manage neovascular AMD. ^{1 2 5 6 7}

Who Is on the Research Team?

Dilsher Dhoot, MD

Principal Investigator

California Retina Consultants (CRC) - Santa Barbara

Are You a Good Fit for This Trial?

This trial is for individuals over 50 years old with a new diagnosis of Neovascular Age-Related Macular Degeneration (nAMD) and have not been treated for it. They must have good vision in at least one eye, with a visual acuity score close to 20/20. People can't join if they only have one working eye or very poor vision in their other eye.

Inclusion Criteria

I am over 50 years old.

My vision, with correction, is about 20/20.

Have an increase of at least 10 ETDRS letters of Best Corrected Visual Acuity (BCVA) from Screening (Visit 1) BCVA

Exclusion Criteria

Have evidence of a scar, fibrosis, or atrophy of > 50% of the total lesion in the study eye

Monocular subjects or a Best Corrected Visual Acuity (BCVA) score of 20/200 in fellow eye at screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the OTX-TKI (axitinib implant) for neovascular age-related macular degeneration

36 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

68 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aflibercept
• OTX-TKI (axitinib implant)

Trial Overview The study tests the effectiveness and safety of an implant called OTX-TKI (axitinib implant), which is placed inside the eye, against Aflibercept, an existing treatment for nAMD. The goal is to see how well these treatments help maintain or improve vision.

How Is the Trial Designed?

Group I: OTX-TKI (axitinib implant) Experimental Treatment 1 Intervention

Group II: Control Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Ocular Therapeutix, Inc.

Lead Sponsor

Trials

55

Recruited

6,400+

Fortrea

Collaborator

Trials

8

Recruited

2,500+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Fortrea

Industry Sponsor

Trials

22

Recruited

5,800+

Published Research Related to This Trial

Axitinib significantly inhibited choroidal neovascularization (CNV) growth by 70.1% in a mouse model of neovascular age-related macular degeneration (AMD), demonstrating its potential efficacy as a treatment.

The drug also caused a substantial regression of established CNV lesions, reducing their area by 71.1%, indicating that axitinib could be a promising therapeutic option for patients with neovascular AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiangiogenic effects of axitinib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, on laser-induced choroidal neovascularization in mice. Kang, S., Roh, CR., Cho, WK., et al.[2018]

In the VISION-1 trial involving 1186 patients, pegaptanib, a VEGF inhibitor, significantly helped maintain visual acuity in patients with neovascular age-related macular degeneration, with 70% of those receiving the 0.3 mg dose losing fewer than 15 letters of visual acuity compared to 55% in the sham group.

While pegaptanib showed no serious systemic side effects, it did lead to more ocular adverse effects, such as vitreous floaters and inflammation, indicating a need for ongoing improvements in treatment options for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegaptanib: the first antiangiogenic agent approved for neovascular macular degeneration. Doggrell, SA.[2019]

A 57-year-old male with metastatic renal cell carcinoma developed impaired retinal circulation after 2 years of axitinib treatment, indicating a novel ocular adverse event associated with this medication.

After discontinuing axitinib and switching to temsirolimus, the patient's retinal symptoms improved, but his visual acuity declined, highlighting the need for clinicians to monitor for potential retinal complications in patients receiving axitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impaired Retinal Circulation during Axitinib Treatment for Metastatic Renal Cell Carcinoma. Kimura, M., Kusuhara, S., Tagami, M., et al.[2022]

In a phase I study involving 48 healthy volunteers, regorafenib eye drops were found to be safe and well tolerated, with no significant adverse effects on the eye or systemic health, indicating a favorable safety profile for further clinical studies.

The systemic exposure to regorafenib from eye drops was significantly lower (600-700 times) than that from oral administration, suggesting a targeted delivery method that minimizes systemic side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical administration of regorafenib eye drops: phase I dose-escalation study in healthy volunteers. Zimmermann, T., Höchel, J., Becka, M., et al.[2021]

In a Phase 1 study involving 35 participants with neovascular age-related macular degeneration, the oral treatment X-82 showed promising results, with 71% of participants maintaining or improving their visual acuity after 24 weeks, and 60% requiring no anti-VEGF injections.

While X-82 was associated with some adverse events, such as diarrhea and nausea, these were generally mild and reversible, indicating that liver function monitoring is necessary but the treatment could be a viable alternative to more invasive injection therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Tyrosine Kinase Inhibitor for Neovascular Age-Related Macular Degeneration: A Phase 1 Dose-Escalation Study. Jackson, TL., Boyer, D., Brown, DM., et al.[2019]

Acrizanib (LHA510) is a promising new topical treatment for wet age-related macular degeneration, offering a noninvasive alternative to the current standard of care that requires injections.

In rodent models of choroidal neovascularization, acrizanib demonstrated strong potency and efficacy, with minimal systemic exposure and a favorable pharmacokinetic profile in rabbits, suggesting it could be a safe and effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Discovery of N-(1-Methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6- ((methylamino)methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide (Acrizanib), a VEGFR-2 Inhibitor Specifically Designed for Topical Ocular Delivery, as a Therapy for Neovascular Age-Related Macular Degeneration. Adams, CM., Anderson, K., Artman, G., et al.[2019]

Axitinib is an oral medication that inhibits key receptors involved in tumor growth and has shown activity against various solid tumors, including thyroid, pancreatic, lung, and breast cancers, based on Phase II trials.

While common side effects include fatigue and hypertension, axitinib was generally well tolerated, and larger randomized studies were underway to further evaluate its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. Choueiri, TK.[2018]

In a 6-week study involving 30 treatment-naive patients with neovascular age-related macular degeneration, AKST4290 (400 mg orally twice daily) led to a significant improvement in best-corrected visual acuity (BCVA), with an average gain of +7.0 letters and 82.8% of patients showing stable or improved vision.

The treatment was well-tolerated, with no severe or serious adverse events reported, indicating that AKST4290 is safe for use and supports the need for further research in larger, randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAFETY AND THERAPEUTIC EFFECTS OF ORALLY ADMINISTERED AKST4290 IN NEWLY DIAGNOSED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION. Stewart, MW., Garg, S., Newman, EM., et al.[2022]

A single suprachoroidal (SC) injection of axitinib resulted in significantly higher drug exposure in the posterior eye cup compared to intravitreal injection, suggesting better targeting of the affected areas in the eye.

Axitinib maintained sustained levels in the retinal pigment epithelium-choroid-sclera and retina for up to 91 days, indicating its potential as a long-acting treatment for neovascular age-related macular degeneration, which could reduce the frequency of treatments compared to current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Long-Lasting Potential of Suprachoroidal Axitinib Suspension Via Ocular and Systemic Disposition in Rabbits. Kansara, VS., Muya, LW., Ciulla, TA.[2021]

Citations

1. ocutx.com ocutx.com/pipeline/axpaxli/

AXPAXLI™ | Advanced Sustained-Release Treatment for ... AXPAXLI aims to treat patients with only 1-2 injections per year while maintaining disease control and preserving visual acuity.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06495918

NCT06495918 | Study to Evaluate the Efficacy and Safety ... Study to evaluate the efficacy and safety of intravitreal OTX-TKI (Axitinib Implant) in subjects with neovascular age-related macular degeneration.

3. biospace.com biospace.com/press-releases/ocular-therapeutix-achieves-target-randomization-of-555-subjects-in-sol-r

Ocular Therapeutix™ Achieves Target Randomization of ... AXPAXLI is currently in Phase 3 clinical trials for wet age-related macular degeneration (wet AMD), with a Phase 3 clinical program for non ...

4. modernretina.com modernretina.com/view/peter-kaiser-md-discusses-otx-tki-a-new-treatment-for-wet-amd-introduced-by-ocular-therapeutics

Peter Kaiser, MD, discusses OTX-TKI, a new treatment for ... This innovative treatment for wet age-related macular degeneration (AMD) offers a unique approach with slow drug release lasting up to 9 months.

5. healio.com healio.com/news/ophthalmology/20241011/otxtki-shows-durable-results-in-treatment-of-neovascular-amd

OTX-TKI shows durable results in treatment of neovascular ... OTX-TKI led to an 89% reduction in anti-VEGF treatment burden. CARLSBAD, Calif. — A sustained-release intravitreal hydrogel implant containing ...

6. iovs.arvojournals.org iovs.arvojournals.org/article.aspx?articleid=2786043

U.S. Phase 1 Study of Intravitreal Axitinib Implant (OTX-TKI) for ... The study was designed to assess the safety, tolerability, and biological activity of a single OTX-TKI implant in nAMD patients.

7. modernretina.com modernretina.com/view/rwc-2024-week-52-safety-and-efficacy-data-from-the-us-phase-1-trial-of-otx-tki

RWC 2024: Week 52 safety and efficacy data from the US ... In this trial, the safety data revealed that AXPAXLI was generally well tolerated with no new safety signals that were unexpected.