AVD-104 for Age-Related Macular Degeneration

(SIGLEC Trial)

Not currently recruiting at 57 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AVD-104 for individuals with geographic atrophy, a condition causing vision loss related to age-related macular degeneration (AMD). The researchers aim to evaluate the safety and efficacy of AVD-104, with some participants receiving varying doses or another treatment called Avacincaptad. This trial may suit those with AMD experiencing vision issues that impact daily life, such as difficulty reading or recognizing faces. Participants will receive eye injections and will be monitored over time to assess the treatment's effects. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that AVD-104 is generally safe for treating geographic atrophy, a condition related to age-related macular degeneration. Earlier studies found no serious side effects linked to the drug, even at higher doses. Patients did not experience major eye-related or whole-body side effects.

Similarly, researchers have studied Avacincaptad for related eye conditions. Real-world experiences and studies indicate it is safe to use. Like AVD-104, Avacincaptad was not associated with significant adverse effects in these studies.

Both treatments appear well-tolerated, suggesting that participants in this trial might expect similar safety outcomes. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AVD-104 for age-related macular degeneration because it offers a potentially more effective approach compared to current treatments like anti-VEGF injections. AVD-104 is unique due to its new mechanism of action that targets different pathways involved in the disease process, which could lead to better preservation of vision. Additionally, the trial explores both high and low doses, with varying injection frequencies, offering a chance to tailor treatment to patient needs and potentially improve outcomes. This flexibility in dosing could mean more personalized and effective care for patients.

What evidence suggests that this trial's treatments could be effective for age-related macular degeneration?

Research shows that AVD-104 holds promise in treating geographic atrophy, a condition linked to age-related macular degeneration. Early studies found that AVD-104, a tiny sugar-like particle, was well-tolerated by patients, with no serious side effects. This suggests it could be safe and effective. In this trial, participants may receive either high-dose or low-dose AVD-104.

For avacincaptad, another treatment option in this trial, studies have shown it significantly slows the growth of geographic atrophy over 12 months. Participants experienced less worsening of their condition compared to those who did not receive treatment, making it a promising option. Both treatments aim to slow the disease's progression, offering hope for those affected by this vision-threatening condition. ^{1 2 3 6 7}

Who Is on the Research Team?

David Callanan, MD

Principal Investigator

Aviceda Therapeutics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05839041

NCT05839041 | A Multiple Dose Study of AVD-104 for ... A multi-center, double masked, randomized trial to evaluate the treatment effect of AVD-104 on participants with geographic atrophy secondary to macular ...

2. avicedarx.com avicedarx.com/company-updates

Company Updates Aviceda Announces AVD-104, a Novel Glycomimetic Nanoparticle, Demonstrates Continued Clinical Safety in the Treatment of Geographic Atrophy Secondary to Macular ...

3. modernretina.com modernretina.com/view/enrollment-complete-of-phase-2b-of-siglec-study-to-assess-safety-and-efficacy-of-avd-104-for-ga-secondary-to-amd

Enrollment complete of phase 2b of SIGLEC study to ... The study will assess the safety and efficacy of AVD-104, the company's formulation designed to treat geographic atrophy (GA) secondary to age-related macular ...

4. healio.com healio.com/news/ophthalmology/20250328/latest-data-show-progress-of-ga-therapies-in-the-pipeline

Latest data show progress of GA therapies in the pipeline AVD-104 for geographic atrophy secondary to age-related macular degeneration: A review of the phase 2a SIGLEC findings and an overview of ...

5. firstwordpharma.com firstwordpharma.com/story/5818933

Aviceda Therapeutics Announces Topline Data from Part 1 ... AVD-104 was well-tolerated in all patients, with no drug-related ocular or systemic serious adverse events detected.

6. healio.com healio.com/news/optometry/20240119/aviceda-reports-positive-topline-data-for-avd104-in-patients-with-geographic-atrophy

Aviceda reports positive topline data for AVD-104 in ... Reduction in GA lesion progression at 3 months was greater than historical standard-of-care outcomes. No drug-related ocular or systemic ...

7. iovs.arvojournals.org iovs.arvojournals.org/article.aspx?articleid=2808119

Fundus Hyperautofluorescence and Autofluorescence ... - IOVS Safety was positive, with no dose-limiting toxicity, ocular SAEs, or drug-related systemic SAEs observed. Conclusions : Among patients with GA secondary to AMD ...