Axitinib Implant for Age-Related Macular Degeneration

Not currently recruiting at 101 trial locations

Overseen By Nichole Wilkes

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ocular Therapeutix, Inc.

Must be taking: Aflibercept

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: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new implant called OTX-TKI (also known as the Axitinib Implant) for individuals with neovascular age-related macular degeneration (nAMD). The researchers aim to determine if this implant can improve or stabilize vision more effectively than standard treatments, such as aflibercept injections. Participants may receive different treatments, including the OTX-TKI implant or varying doses of aflibercept. Ideal candidates have recently been diagnosed with nAMD and may have already tried aflibercept injections. 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 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 there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that the OTX-TKI implant, which contains the drug Axitinib, is generally well-tolerated. Previous research reported no unexpected safety issues, indicating that users did not encounter new or surprising problems. The evidence suggests that most patients handle the treatment well, which bodes well for its safety in humans. ^{1 2 3 4 5}

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

Researchers are excited about OTX-TKI for age-related macular degeneration because it offers a novel delivery method as an implant, which could potentially reduce the frequency of treatments compared to standard care injections like Aflibercept. This implant slowly releases Axitinib, a tyrosine kinase inhibitor, directly into the eye, which might enhance the treatment's effectiveness and duration. Unlike other treatments that require regular injections, this innovative approach aims to provide sustained efficacy, improving convenience and adherence for patients.

What evidence suggests that this trial's treatments could be effective for age-related macular degeneration?

Research shows that OTX-TKI, a small implant containing the drug axitinib, holds promise for treating neovascular age-related macular degeneration (AMD). Earlier studies demonstrated a reduction in the need for additional treatments by 89%. In this trial, participants may receive the OTX-TKI implant, which releases the medication slowly over up to nine months, potentially reducing the number of injections needed each year. Specifically, patients maintained disease control and stable vision with just one or two injections annually. These early results suggest that OTX-TKI might effectively manage wet AMD. ^{1 5 6 7 8}

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 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.

I have not received any treatment for my wet AMD affecting the center of my vision.

Have provided written consent

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• OTX-TKI

Trial Overview 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.

How Is the Trial Designed?

Group I: OTX-TKI Re-dose Experimental Treatment 1 Intervention

Group II: Aflibercept 8mg high dose Experimental Treatment 1 Intervention

Group III: Aflibercept 2mg on label Active Control 1 Intervention

Who Is Running the Clinical Trial?

Ocular Therapeutix, Inc.

Lead Sponsor

Trials

55

Recruited

6,400+

Fortrea

Industry Sponsor

Trials

22

Recruited

5,800+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

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 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]

Axitinib-loaded PLGA nanoparticles were successfully developed to provide a sustained release formulation, potentially reducing the need for frequent intravitreal injections in treating age-related macular degeneration (AMD).

The nanoparticles demonstrated low cytotoxicity to retinal cells (<12% at 10 μM), effective cellular uptake, and significant antiangiogenic effects by inhibiting vascular endothelial growth factor (VEGF) activity, indicating their potential as a safe and effective treatment option for AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib-Loaded Poly(Lactic-Co-Glycolic Acid) Nanoparticles for Age-Related Macular Degeneration: Formulation Development and In Vitro Characterization. Narvekar, P., Bhatt, P., Fnu, G., et al.[2020]

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]

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 study of 253 patients with neovascular age-related macular degeneration (NV-AMD) treated with pegaptanib sodium, over 90% of patients experienced less than 15 letters of vision loss after 24 and 54 weeks, which is significantly better than the 70% reported in the VISION trial.

Pegaptanib was well tolerated among patients, with no serious adverse effects such as endophthalmitis or retinal detachment reported, indicating a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal pegaptanib sodium for choroidal neovascularisation secondary to age-related macular degeneration: Pan-European experience. Sivaprasad, S., Hykin, P., Saeed, A., et al.[2016]

Axitinib, an oral medication that inhibits both VEGF and PDGF pathways, showed superior inhibition of neovascularization compared to traditional anti-VEGF treatments in various in vitro models.

In a rat model of choroidal neovascularization, axitinib demonstrated effective results at a low dose of 0.875 mg/day, suggesting it could be a promising alternative for treating wet Age-related Macular Degeneration (AMD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib inhibits retinal and choroidal neovascularization in in vitro and in vivo models. Giddabasappa, A., Lalwani, K., Norberg, R., et al.[2018]

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]

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. 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.

4. 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 ...

5. retinalphysician.com retinalphysician.com/issues/2023/october/clinical-trial-download/

Twelve-month Data From a Phase 1 Clinical Trial of OTX- ... OTX-TKI is being evaluated for the treatment of wet age-related macular degeneration (wet AMD), diabetic retinopathy (DR), and other retinal diseases.

6. investors.ocutx.com investors.ocutx.com/static-files/00a24bfa-e147-49fc-86cf-9135b9e4f37f

OTX-TKI, Sustained-Release Axitinib Hydrogel Implant, for ... Abbreviations: AMD=age-related macular degeneration; BCVA=best corrected ... ▫ Safety data* showed OTX-TKI was generally well-tolerated. ▫ Implant ...

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.

8. 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.