Axitinib Implant for Age-Related Macular Degeneration

Recruiting at 95 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

825 Participants Needed

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. ^{1 2 3 4 5}

How 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. ^{1 4 6 7 8}

Research Team

Dilsher Dhoot, MD

Principal Investigator

California Retina Consultants (CRC) - Santa Barbara

Eligibility 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.

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Oral Tyrosine Kinase Inhibitor for Neovascular Age-Related Macular Degeneration: A Phase 1 Dose-Escalation Study. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Intravitreal pegaptanib sodium for choroidal neovascularisation secondary to age-related macular degeneration: Pan-European experience. [2016]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Impaired Retinal Circulation during Axitinib Treatment for Metastatic Renal Cell Carcinoma. [2022]

4. England 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. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Axitinib-Loaded Poly(Lactic-Co-Glycolic Acid) Nanoparticles for Age-Related Macular Degeneration: Formulation Development and In Vitro Characterization. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Axitinib inhibits retinal and choroidal neovascularization in in vitro and in vivo models. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Long-Lasting Potential of Suprachoroidal Axitinib Suspension Via Ocular and Systemic Disposition in Rabbits. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

SAFETY AND THERAPEUTIC EFFECTS OF ORALLY ADMINISTERED AKST4290 IN NEWLY DIAGNOSED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION. [2022]