AIV007 for Age-Related Macular Degeneration/Diabetic Macular Edema

(DME Trial)

Not currently recruiting at 6 trial locations

Overseen By Jennifer Wang, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AiViva BioPharma, Inc.

Must be taking: Anti-VEGF

Disqualifiers: Uncontrolled IOP, Poorly controlled diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gel called AIV007, delivered by injection near the eye. The trial aims to assess the safety and effectiveness of this treatment in individuals with specific eye conditions, such as neovascular age-related macular degeneration (a condition causing vision loss) or diabetic macular edema (swelling in the retina due to diabetes). Individuals treated with anti-VEGF injections for their eye condition in the last two years might be suitable candidates. As a Phase 1 trial, participants have the opportunity to be among the first to receive this new treatment and assist researchers in understanding its effects in people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must have received anti-VEGF treatment at least 6 weeks before the trial and cannot participate if you've been in another investigational study within 60 days before screening.

Is there any evidence suggesting that AIV007 is likely to be safe for humans?

Research shows that AIV007 remains in the early testing stages to determine its safety for people. As a result, there is limited information about how well people tolerate it. In this Phase 1 trial, the primary goal is to ensure AIV007's safety for humans.

The trial administers different doses of AIV007 as injections around the eye. Testing these doses helps researchers observe the body's reactions and identify any side effects. Since the trial is just beginning, specific safety information is not yet available.

Although clear evidence from this trial is not yet available, Phase 1 trials typically aim to identify risks and confirm the treatment's safety before proceeding to larger studies. Researchers will closely monitor participants to ensure their safety throughout the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Most treatments for age-related macular degeneration (AMD) and diabetic macular edema (DME), like anti-VEGF injections, focus on stopping abnormal blood vessel growth and leakage in the eye. AIV007 is unique because it is delivered via a periocular injection, which means it's administered around the eye rather than directly into it, potentially reducing discomfort and complications. Researchers are excited about AIV007 because it offers multiple dosing options, including low, intermediate, and high doses, allowing for more personalized treatment approaches. This new method and flexibility could improve patient comfort and treatment outcomes compared to current options.

What evidence suggests that AIV007 might be an effective treatment for age-related macular degeneration or diabetic macular edema?

Research has shown that AIV007 could be a promising treatment for certain eye conditions, specifically neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). This trial will evaluate different dosages of AIV007, which involves a gel injected around the eye. This method is designed to be less invasive and last longer than other treatments. Early studies suggest that AIV007 is safe and may effectively manage these conditions. The trial aims to reduce the need for frequent eye injections by offering a longer-lasting solution. While more research is needed, initial results indicate it could be a valuable option for people with nAMD and DME. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 21-90 with diabetic macular edema (DME) or neovascular age-related macular degeneration (nAMD). Participants must have had previous anti-VEGF treatments and show responsiveness. Exclusions include uncontrolled eye pressure, severe myopia, recent ocular infections or inflammations, poorly controlled diabetes, and hypersensitivity to study treatment components.

Inclusion Criteria

My condition responds to anti-VEGF treatment.

Subject must provide written informed consent before any study-related procedures are performed

I have diabetes and significant eye swelling affecting my vision.

Exclusion Criteria

Uncontrolled IOP (> 25 mmHg)

Spherical equivalent for refractive error in the study eye of worse than 8.0 diopters of myopia

I haven't had eye infections or inflammation recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive periocular injections of AIV007 at various doses

24 weeks

Multiple visits for injections and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AIV007

Trial Overview

The trial tests the safety and effectiveness of a gel suspension called AIV007 administered around the eye in patients with nAMD or DME. It aims to understand how long the drug's effects last and how it moves through the body after being given.

How Is the Trial Designed?

Group I: AIV007 low dose Experimental Treatment 1 Intervention

Periocular injection, low dose

Group II: AIV007 intermediate dose 4 Experimental Treatment 1 Intervention

Periocular injection, intermediate dose 4

Group III: AIV007 intermediate dose 3 Experimental Treatment 1 Intervention

Periocular injection, intermediate dose 3

Group IV: AIV007 intermediate dose 2 Experimental Treatment 1 Intervention

Periocular injection, intermediate dose 2

Group V: AIV007 intermediate dose 1 Experimental Treatment 1 Intervention

Periocular injection, intermediate dose 1

Group VI: AIV007 High dose Experimental Treatment 1 Intervention

Periocular injection, high dose

Who Is Running the Clinical Trial?

AiViva BioPharma, Inc.

Lead Sponsor

Trials

6

Recruited

90+

Published Research Related to This Trial

The phase 1 trial involving 8 subjects with advanced wet AMD showed that subretinal injection of rAAV.sFlt-1 was well tolerated over a 36-month period, with no significant ocular or systemic safety concerns reported.

Exploratory data indicated that the condition of wet AMD remained stable throughout the study, suggesting that rAAV.sFlt-1 may be a promising candidate for further research in treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene Therapy in Neovascular Age-related Macular Degeneration: Three-Year Follow-up of a Phase 1 Randomized Dose Escalation Trial. Constable, IJ., Lai, CM., Magno, AL., et al.[2017]

The incidence of nonocular serious adverse events in patients treated with intravitreal VEGF inhibitors for neovascular age-related macular degeneration varies widely, with reports ranging from 0% to 39.3%, indicating a potential risk that needs further investigation.

Patients with a history of cardiovascular issues, particularly stroke, may be at an increased risk for serious nonocular adverse events when treated with anti-VEGF agents, suggesting that caution is warranted in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic safety of intravitreal anti-vascular endothelial growth factor agents in age-related macular degeneration. Dedania, VS., Bakri, SJ.[2018]

Intravitreal aflibercept injection (IAI) demonstrated a safety profile comparable to control treatments across various retinal diseases, with no significant differences in rates of ocular and systemic adverse events among over 4000 patients in 10 clinical trials.

IAI was generally well tolerated, showing lower rates of intraocular inflammation and endophthalmitis compared to controls, indicating its efficacy and safety for treating conditions like neovascular age-related macular degeneration and diabetic macular edema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Review of Ocular and Systemic Safety Events with Intravitreal Aflibercept Injection in Randomized Controlled Trials. Kitchens, JW., Do, DV., Boyer, DS., et al.[2022]

A comprehensive analysis of over 10 million adverse event reports revealed significant ocular adverse events associated with anti-VEGF drugs, highlighting specific risks for each drug: ranibizumab is linked to macular ischaemia and retinal pigment epithelial tear, aflibercept to increased intraocular pressure and endophthalmitis, and brolucizumab to retinal vasculitis and retinal artery occlusion.

The study emphasizes the importance of considering a patient's medical history when prescribing anti-VEGF treatments to minimize the risk of these serious ocular adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular adverse events associated with anti-VEGF therapy: A pharmacovigilance study of the FDA adverse event reporting system (FAERS). Ma, P., Pan, X., Liu, R., et al.[2022]

In a study of 593,277 patients with late dry age-related macular degeneration (dAMD), it was found that the majority had mild disease (64.4%) or intermediate disease (29.4%), with visual acuity (VA) decreasing as the disease progressed.

The annual probability of stable dAMD was high (82.1% for GA without subfoveal involvement to 92.3% for GA with subfoveal involvement), but the risk of progression to geographic atrophy or neovascular AMD increased significantly with disease severity, highlighting the need for effective treatments as patients advance in disease stage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dry Age-Related Macular Degeneration: Distribution of Visual Acuity and Progression Risk in a Large Registry. Leng, T., Schwartz, J., Nimke, D., et al.[2023]

In a study of 223 patients with neovascular age-related macular degeneration (nAMD) receiving anti-VEGF injections for over 5 years, there was no significant difference in best visual acuity (BVA) changes based on macular atrophy (MA) status.

Both groups, regardless of MA presence, experienced similar visual outcomes after 5 to 7 years of treatment, indicating that baseline MA status does not affect the effectiveness of anti-VEGF therapy in improving vision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Visual Outcomes in Neovascular Age-Related Macular Degeneration Eyes With Baseline Macular Atrophy on Anti-Vascular Endothelial Growth Factor Treatment. Foster, MJ., Shaia, J., Maatouk, CM., et al.[2023]

In a study of 128 patients with intermediate dry age-related macular degeneration (AMD), intravitreal aflibercept injections did not significantly reduce the conversion rate to exudative AMD (eAMD) compared to a sham treatment after 24 months, with conversion rates of 9.5% in the treatment group and 10.9% in the sham group.

The safety profile of aflibercept was consistent with previous studies, indicating that while it may not prevent conversion to eAMD, it is safe for use in patients at high risk for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Aflibercept Injection vs Sham as Prophylaxis Against Conversion to Exudative Age-Related Macular Degeneration in High-risk Eyes: A Randomized Clinical Trial. Heier, JS., Brown, DM., Shah, SP., et al.[2022]

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world, particularly affecting patients with neovascular AMD (nAMD) who currently rely on frequent and invasive anti-VEGF injections, which can lead to complications and treatment tolerance.

There is a pressing need for new therapies, especially for non-neovascular AMD, which accounts for 90% of cases and lacks approved treatments, highlighting the importance of developing improved drug delivery methods and sustainable clinical effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies and their delivery for treating age-related macular degeneration. Thomas, CN., Sim, DA., Lee, WH., et al.[2022]

Intravitreal injections of anti-VEGF drugs like Bevacizumab, Ranibizumab, and Aflibercept are effective in treating neovascular age-related macular degeneration, helping to slow disease progression and improve vision.

Despite their efficacy, these injections carry risks of complications such as infection, inflammation, and increased intraocular pressure, highlighting the need for careful consideration of their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-vascular endothelial growth factor drugs safety and efficacy in ophthalmic diseases. Ventrice, P., Leporini, C., Aloe, JF., et al.[2021]

In a post hoc analysis of the HARBOR trial involving 700 patients with neovascular age-related macular degeneration (nAMD), different types of macular neovascularization (MNV) were associated with varying visual acuity outcomes after treatment with ranibizumab.

Type 1 MNV lesions had the best baseline and 24-month visual acuity, while type 2/mixed lesions showed the greatest improvement in visual acuity after treatment, highlighting the importance of anatomic classification in predicting treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Macular neovascularization lesion type and vision outcomes in neovascular age-related macular degeneration: post hoc analysis of HARBOR. Freund, KB., Staurenghi, G., Jung, JJ., et al.[2022]

In a study of 168 patients with neovascular age-related macular degeneration (nAMD) receiving multiple intravitreal ranibizumab injections, there was no significant change in retinal nerve fiber layer (RNFL) thickness compared to healthy controls, indicating that the treatment does not adversely affect this aspect of retinal health.

Regardless of the number of injections (3-10, 10-20, or ≥20), RNFL thickness remained stable, and intraocular pressure levels did not significantly change after injections, suggesting that repeated ranibizumab treatments are safe in terms of RNFL integrity and pressure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal Nerve Fiber Layer Thickness Changes in Age-Related Macular Degeneration Treated with Multiple Intravitreal Ranibizumab. Sengul, EA., Artunay, O., Kumral, ET., et al.[2018]

A study involving 502 patients with neovascular age-related macular degeneration (nAMD) demonstrated that machine learning models using baseline OCT features and clinical data can effectively predict visual acuity outcomes after treatment with ranibizumab, with the Lasso model showing a mean R2 of 0.46.

These AI-based models outperformed traditional methods in predicting treatment response, indicating their potential for improving personalized treatment strategies in nAMD, although further development is needed for clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Machine Learning to Predict Response to Ranibizumab in Neovascular Age-Related Macular Degeneration. Maunz, A., Barras, L., Kawczynski, MG., et al.[2023]

In a study of 13,859 patients with neovascular age-related macular degeneration treated with anti-VEGF drugs, all three medications (bevacizumab, ranibizumab, and aflibercept) showed similar improvements in visual acuity after one year of treatment.

Despite initial differences in visual acuity outcomes, after adjusting for various factors, there were no significant differences in the overall effectiveness of the three drugs, although bevacizumab had a higher percentage of patients achieving a ≥3-line improvement in vision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Vision in Age-Related Macular Degeneration Patients Treated with Single Anti-VEGF Drug Type for 1 Year in the IRIS Registry. Rao, P., Lum, F., Wood, K., et al.[2019]

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The company has developed two drugs—AIV007 that would be ideal for treating specific eye disorders and tumors, and AIV001 that can treat wound healing at a site ...