AVD-104 for Age-Related Macular Degeneration

(SIGLEC Trial)

Recruiting at 56 trial locations

Overseen By Keri Marchitto

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Aviceda Therapeutics, Inc.

Disqualifiers: Exudative AMD, Choroidal neovascularization, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

300 Participants Needed

Trial Summary

What is the purpose of this trial?

Investigate the Safety, Pharmacokinetics, and Treatment effects of Single and Multi-dose of Intravitreal AVD-104 in participants with geographic atrophy secondary to age-related macular degeneration.

Will I have to stop taking my current medications?

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 effectiveness of the drug AVD-104 for age-related macular degeneration?

Research shows that anti-VEGF (antivascular endothelial growth factor) injections, similar to AVD-104, have been effective in treating age-related macular degeneration by improving vision and reducing disease progression. ^{1 2 3 4 5}

Is AVD-104 safe for humans?

The safety of anti-VEGF treatments, like bevacizumab, for age-related macular degeneration has been studied, showing some concerns about non-eye-related side effects, especially in people with heart conditions. However, these treatments are generally considered safe for most patients. ^{6 7 8 9 10}

Research Team

David Callanan, MD

Principal Investigator

Aviceda Therapeutics

Eligibility Criteria

This trial is for people with a specific eye condition called Geographic Atrophy (GA) due to Age-Related Macular Degeneration (AMD). Participants must have certain levels of vision clarity, as measured by an eye chart. They should not have the wet form of AMD or other eye conditions that might need treatment during the study.

Inclusion Criteria

My eye condition can be fully seen and imaged without touching the optic nerve area.

I have been diagnosed with a type of age-related macular degeneration that does not affect the center of my vision.

Part 1: BCVA in the study eye using ETDRS Chart Visual Acuity Scale (VAS) of 5 to 55 letters (equivalent to Snellen VA of approximately 20/800 - 20/80)

Exclusion Criteria

I don't have eye conditions needing surgery other than GA from AMD.

I have wet AMD or CNV diagnosed by specific eye scans.

My study eye has specific eye conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Single Dose Treatment

Participants receive a single intravitreal injection of AVD-104 at one of 4 escalating doses and are followed for safety observation.

3 months

1 visit (in-person) for injection, followed by regular safety visits

Part 2: Multiple Dose Treatment

Participants are randomized to receive either high dose AVD-104 bimonthly, low dose AVD-104 monthly, or avacincaptad monthly for 24 months.

24 months

Bimonthly or monthly visits (in-person) for injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• AVD-104
• Sham injection

Trial Overview The study tests multiple doses of AVD-104, given through injections into the eye, to see if it's safe and effective for treating GA in AMD patients. Some participants will receive a sham injection instead to serve as a comparison group.

Participant Groups

Group I: Part 1 Experimental Treatment 1 Intervention

Participants will receive a single intravitreal injection of AVD-104 at one of 4 escalating doses. All participants will be followed up for safety until Month 3.

Group II: Part 2: High dose AVD-104 Active Control 1 Intervention

100 participants will be randomized and treated with bimonthly intravitreal injections of high-dose AVD-104 for the first 12 months. They will continue bimonthly injections for months 13-24.

Group III: Part 2: Avacincaptad Active Control 1 Intervention

100 participants will be randomized to receive monthly injections of avacincaptad (2 mg. intravitreal)

Group IV: Part 2: Low dose AVD-104 Active Control 1 Intervention

100 participants will be randomized and treated with monthly intravitreal injections of low dose AVD-104 for 24 months.

Who Is Running the Clinical Trial?

Aviceda Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

320+

Findings from Research

In a study of 1017 patients treated with intravitreal ranibizumab for neovascular age-related macular degeneration (AMD) over 4 years, 50% of patients maintained a vision level of 6/18 or better, indicating significant long-term efficacy of the treatment.

The average number of injections required increased over time, with patients receiving approximately 13.7 injections by the end of the 4-year period, highlighting the ongoing need for treatment and the importance of long-term follow-up in managing AMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring the benefit of 4 years of intravitreal ranibizumab treatment for neovascular age-related macular degeneration. Pushpoth, S., Sykakis, E., Merchant, K., et al.[2015]

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]

Only about 0.1% of the Polish population requires treatment for neovascular age-related macular degeneration (nAMD) when considering patients without severe irreversible eye damage, indicating a relatively low prevalence of this condition needing intervention.

The COVID-19 pandemic significantly impacted the enrollment in the national AMD therapeutic program, with a notable decrease in monthly enrollments, highlighting potential barriers to treatment access during health crises.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Need for Treatment of Neovascular Age-Related Macular Degeneration: A Study Based on the Polish National Registry. Teper, SJ., Nowińska, A., Figurska, M., et al.[2022]

A study of 2100 AMD patients who received bevacizumab injections after experiencing an acute myocardial infarct (MI) found that these patients had significantly higher mortality rates compared to similar patients who did not receive anti-VEGF treatment.

Specifically, the risk of mortality was notably increased within the first 3 months after starting bevacizumab treatment, suggesting that caution is necessary when prescribing this medication to AMD patients with a history of MI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mortality associated with bevacizumab intravitreal injections in age-related macular degeneration patients after acute myocardial infarct: a retrospective population-based survival analysis. Hanhart, J., Comaneshter, DS., Freier-Dror, Y., et al.[2018]

Intravitreal injections of antivascular endothelial growth factor (VEGF) drugs, such as pegaptanib and ranibizumab, are generally safe and effective treatments for neovascular age-related macular degeneration (AMD) for up to 2-3 years, based on current literature.

While pegaptanib and ranibizumab have strong evidence supporting their efficacy, the evidence for bevacizumab is not as robust, indicating a need for further research on its safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of intravitreal anti-VEGF injections for age-related macular degeneration. Jeganathan, VS., Verma, N.[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]

References

1. England pubmed.ncbi.nlm.nih.gov

Current and upcoming anti-VEGF therapies and dosing strategies for the treatment of neovascular AMD: a comparative review. [2020]

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

Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration in treatment-naive patients. [2015]

3. England pubmed.ncbi.nlm.nih.gov

Measuring the benefit of 4 years of intravitreal ranibizumab treatment for neovascular age-related macular degeneration. [2015]

4. 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]

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

The Need for Treatment of Neovascular Age-Related Macular Degeneration: A Study Based on the Polish National Registry. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Mortality associated with bevacizumab intravitreal injections in age-related macular degeneration patients after acute myocardial infarct: a retrospective population-based survival analysis. [2018]

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

Safety and Efficacy of Anti-Vascular Endothelial Growth Factor Therapies for Neovascular Age-Related Macular Degeneration: A Report by the American Academy of Ophthalmology. [2022]

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

Safety and efficacy of intravitreal anti-VEGF injections for age-related macular degeneration. [2022]

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

Palmerston North Interventional Rapid Avastin Treat and Extend (PIRATE) study protocol; meeting the medical retina service needs of our ageing population. [2023]

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

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