AIV007 for Age-Related Macular Degeneration/Diabetic Macular Edema

(DME Trial)

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

19 Participants Needed

Trial Summary

What is the purpose of this trial?

To determine safety, pharmacokinetics, and duration of effect of periocularly administered AIV007 gel suspension in subjects with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME).

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.

What data supports the idea that AIV007 for Age-Related Macular Degeneration/Diabetic Macular Edema is an effective treatment?

The available research does not provide specific data on AIV007 for Age-Related Macular Degeneration or Diabetic Macular Edema. Instead, it discusses other treatments like anti-VEGF drugs, which are commonly used for these conditions. These drugs have shown to help maintain or improve vision in patients with neovascular age-related macular degeneration. However, the research highlights the need for new treatments due to some patients not responding well or developing tolerance to current options. Therefore, while AIV007 might be promising, the provided information does not include specific evidence of its effectiveness. ^{1 2 3 4 5}

What safety data is available for AIV007 treatment?

The provided research does not specifically mention AIV007 or AIV 007. However, it discusses the safety of anti-VEGF drugs, which are used in treating age-related macular degeneration and diabetic macular edema. These drugs, such as bevacizumab, ranibizumab, and aflibercept, have been associated with ocular adverse events like infection, inflammation, increased intraocular pressure, and vitreous hemorrhage. The studies highlight the importance of considering a patient's medical condition to minimize adverse events. ^{6 7 8 9 10}

Is the drug AIV007 a promising treatment for Age-Related Macular Degeneration and Diabetic Macular Edema?

The drug AIV007 is considered promising because it is being studied for its potential to help people with Age-Related Macular Degeneration and Diabetic Macular Edema, which are conditions that can lead to vision loss. Although the specific benefits of AIV007 are not detailed in the provided research, the focus on these conditions suggests that AIV007 could offer new hope for improving or maintaining vision in affected individuals. ^{1 2 11 12 13}

Eligibility Criteria

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

I haven't had eye infections or inflammation recently.

I have received treatments other than anti-VEGF injections for nAMD or DME in my study eye.

Uncontrolled IOP (> 25 mmHg)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

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 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]

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]

References

1. United States 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. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Machine Learning to Predict Response to Ranibizumab in Neovascular Age-Related Macular Degeneration. [2023]

3. United States 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. [2022]

4. United States 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. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Emerging therapies and their delivery for treating age-related macular degeneration. [2022]

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

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

7. United States 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. [2017]

8. India pubmed.ncbi.nlm.nih.gov

Anti-vascular endothelial growth factor drugs safety and efficacy in ophthalmic diseases. [2021]

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

Comprehensive Review of Ocular and Systemic Safety Events with Intravitreal Aflibercept Injection in Randomized Controlled Trials. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Ocular adverse events associated with anti-VEGF therapy: A pharmacovigilance study of the FDA adverse event reporting system (FAERS). [2022]

11. England pubmed.ncbi.nlm.nih.gov

Dry Age-Related Macular Degeneration: Distribution of Visual Acuity and Progression Risk in a Large Registry. [2023]

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

Retinal Nerve Fiber Layer Thickness Changes in Age-Related Macular Degeneration Treated with Multiple Intravitreal Ranibizumab. [2018]

13. Germany pubmed.ncbi.nlm.nih.gov

Macular neovascularization lesion type and vision outcomes in neovascular age-related macular degeneration: post hoc analysis of HARBOR. [2022]