Axitinib Implant for Age-Related Macular Degeneration

Recruiting at 110 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

344 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a small device placed in the eye that releases medication for patients with a severe form of AMD. The medication helps stop abnormal blood vessel growth in the eye, potentially preventing further vision loss. This approach has significantly improved treatment for this condition in recent years.

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.

What data supports the idea that Axitinib Implant for Age-Related Macular Degeneration is an effective treatment?

The available research does not provide direct evidence supporting the effectiveness of the Axitinib Implant specifically for Age-Related Macular Degeneration. However, one study investigated the effects of axitinib on a similar condition in mice, showing that it can impact choroidal neovascularization, which is related to age-related macular degeneration. This suggests potential effectiveness, but more specific research on the Axitinib Implant itself is needed to confirm its benefits for this condition. ^{1 2 3 4 5}

What data supports the effectiveness of the axitinib implant treatment for age-related macular degeneration?

Research shows that axitinib, which blocks certain growth factors involved in blood vessel formation, has been effective in reducing abnormal blood vessel growth in animal models of age-related macular degeneration. ^{1 2 3 4 5}

What safety data exists for the Axitinib Implant for AMD?

Axitinib has been studied primarily as an oral treatment for various cancers, with known side effects including fatigue, hypertension, diarrhea, hand-foot syndrome, and proteinuria. In the context of ocular use, a case of impaired retinal circulation was reported during axitinib treatment for cancer. Animal studies have explored its effects on choroidal neovascularization in AMD models, and its pharmacokinetics have been evaluated in rabbits. However, specific safety data for the axitinib implant in humans for AMD is not detailed in the provided research. ^{1 2 4 6 7}

Is the axitinib implant generally safe for humans?

Axitinib has been used in humans for treating various cancers and is generally well tolerated, but it can cause side effects like fatigue, high blood pressure, diarrhea, and hand-foot syndrome. In one case, it caused impaired retinal circulation, an eye-related side effect, during treatment for kidney cancer. ^{1 2 4 6 7}

Is the drug OTX-TKI (axitinib implant) a promising treatment for age-related macular degeneration?

Yes, OTX-TKI (axitinib implant) is a promising treatment for age-related macular degeneration. It targets and inhibits VEGF, a key factor in the disease, potentially offering long-lasting benefits compared to current treatments. ^{1 2 7 8 9}

How is the axitinib implant different from other drugs for age-related macular degeneration?

The axitinib implant is unique because it delivers the drug directly into the eye, potentially offering longer-lasting effects compared to standard treatments that require frequent injections. It targets multiple VEGF receptors, which are involved in the growth of abnormal blood vessels in the eye, and may provide broader inhibition of these pathways. ^{1 2 7 8 9}

Research Team

Dilsher Dhoot, MD

Principal Investigator

California Retina Consultants (CRC) - Santa Barbara

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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]

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]

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 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 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]

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 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 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]

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

Antiangiogenic effects of axitinib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, on laser-induced choroidal neovascularization in mice. [2018]

3. United States 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. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

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

Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. [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. England pubmed.ncbi.nlm.nih.gov

Topical administration of regorafenib eye drops: phase I dose-escalation study in healthy volunteers. [2021]

9. England pubmed.ncbi.nlm.nih.gov

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