ABI-110 for Wet Age-Related Macular Degeneration

Recruiting at 4 trial locations

Overseen By Wendy Murahashi

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Avirmax Biopharma Inc

Must be taking: Anti-VEGF

Must not be taking: Intravitreal steroids

Disqualifiers: Retinal detachment, Uncontrolled glaucoma, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 105

Duration: 1 day

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ABI-110 (also known as AAV2.N54-VEGF Trap) to determine its safety and tolerability in people with wet macular degeneration (wAMD), a condition that affects vision. The study will explore different doses to identify the optimal amount for future research. Participants should have wAMD, have benefited from anti-VEGF injections, and still require these treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it does require a history of anti-VEGF injections, so you may need to continue those treatments.

Is there any evidence suggesting that ABI-110 is likely to be safe for humans?

Research has shown that ABI-110, the treatment being tested for wet age-related macular degeneration (wAMD), is generally safe for use in the eye. Some patients have experienced mild side effects, such as eye discomfort, but no serious problems have been directly linked to ABI-110.

This study is in its early stages (Phase 1/Phase 2), focusing on how well people tolerate different doses of ABI-110. Early phases like this prioritize ensuring the treatment's safety and understanding the body's response. Researchers are closely monitoring for any side effects.

Prospective participants should know that these trials aim to confirm the treatment's safety before progressing to larger studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ABI-110 because it offers a fresh approach to treating wet age-related macular degeneration (AMD). Unlike current treatments like anti-VEGF injections, which primarily inhibit blood vessel growth, ABI-110 targets a different pathway that could more effectively reduce retinal swelling and improve vision. Additionally, ABI-110 is being tested in multiple doses, allowing researchers to find the optimal balance between efficacy and safety. This innovative approach has the potential to provide better outcomes for patients who do not respond well to existing therapies.

What evidence suggests that ABI-110 might be an effective treatment for wet macular degeneration?

Research has shown that ABI-110 might help treat wet age-related macular degeneration (wAMD). Some patients experienced better vision and less fluid in their eyes. These improvements suggest that ABI-110 could be effective for this condition. The treatment targets the genetic causes of wAMD, potentially offering a long-lasting solution. Although more studies are needed, early results appear promising. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for patients with wet age-related macular degeneration (wAMD), including those with symptomatic macular polypoidal choroidal vasculopathy (PCV). Specific eligibility criteria are not provided, but typically include a confirmed diagnosis and no contraindications for treatment.

Inclusion Criteria

Must be willing and able to provide written, signed informed consent

I am between 50 and 89 years old.

My wet AMD diagnosis, including PCV, is confirmed by a specialized center.

Exclusion Criteria

I haven't had any eye injections except for anti-VEGF in the last 6 months.

I have had gene therapy on my eye.

I have had photodynamic therapy or laser treatment on my eye.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Confirmation of Response

Confirmation of response to EYLEA (aflibercept) before administration of ABI-110

2-4 weeks

Treatment

Single administration of ABI-110 (AAV2.N54-VEGF-Trap) injection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, tolerability, and preliminary efficacy after treatment

104 weeks

Regular visits over 104 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ABI-110

Trial Overview The study tests three different doses of ABI-110, an experimental drug delivered through an eye injection, to evaluate its safety and early effectiveness in treating wAMD and PCV.

How Is the Trial Designed?

Group I: Dose level 3 Experimental Treatment 1 Intervention

High Dose

Group II: Dose level 2 Experimental Treatment 1 Intervention

Medium Dose

Group III: Dose level 1 Experimental Treatment 1 Intervention

Low Dose

ABI-110 is already approved in United States for the following indications:

Approved in United States as ABI-110 for:

• Wet Age-related Macular Degeneration (AMD)
• Polypoidal Choroidal Vasculopathy (PCV)

Who Is Running the Clinical Trial?

Avirmax Biopharma Inc

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

In a clinical trial involving 25 patients with neovascular age-related macular degeneration, the maximum tolerated dose of intravenous VEGF Trap was determined to be 1.0 mg/kg, which effectively reduced excess retinal thickness by about 60%.

While most adverse events were mild to moderate, two patients at the highest dose experienced serious side effects, leading to their withdrawal from the study, highlighting the need for careful dose management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of an IV-administered vascular endothelial growth factor trap for treatment in patients with choroidal neovascularization due to age-related macular degeneration. Nguyen, QD., Shah, SM., Hafiz, G., et al.[2009]

In two phase-3 studies involving 2419 patients with neovascular age-related macular degeneration (AMD), intravitreal aflibercept injections were found to be noninferior to monthly ranibizumab in maintaining vision after one year, with similar rates of patients losing less than 15 letters on the vision chart.

Aflibercept administered every two months after three initial monthly doses showed comparable efficacy and safety to monthly ranibizumab, suggesting it could reduce the frequency of injections and monitoring for patients, which may enhance treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Heier, JS., Brown, DM., Chong, V., et al.[2022]

In a study of 22 patients with refractory neovascular age-related macular degeneration (NVAMD), biweekly intravitreal aflibercept injections led to significant improvements in both visual acuity and central subfield thickness after 14 weeks of treatment.

However, these improvements were not maintained after switching back to monthly dosing, indicating that continuous biweekly treatment may be necessary to sustain the benefits in patients with persistent subretinal fluid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SUSTAINED BIWEEKLY AFLIBERCEPT FOR REFRACTORY NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The Prospective TRISTAR Study. Schneider, EW., Thomas, MK., Recchia, FM., et al.[2023]

A single injection of AAV2 into the eye can continuously deliver anti-VEGF protein, which is crucial for treating neovascular age-related macular degeneration (AMD).

This method offers a long-lasting treatment option, potentially reducing the need for frequent injections typically required in current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-VEGF AAV2 injections: The fewer the better. Byrne, LC.[2019]

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]

The study involved 21 patients with neovascular age-related macular degeneration (AMD) and found that intravitreal injections of VEGF Trap-Eye were well tolerated, with no serious adverse events or intraocular inflammation reported.

Patients receiving the highest doses (2 mg and 4 mg) showed significant improvements in visual acuity, with an average increase of 13.5 letters, and reductions in foveal thickness, indicating the bioactivity of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of intravitreal vascular endothelial growth factor trap-eye in patients with neovascular age-related macular degeneration. Nguyen, QD., Shah, SM., Browning, DJ., et al.[2021]

Anti-VEGF drugs have significantly improved visual outcomes for patients with neovascular age-related macular degeneration (AMD), establishing them as the standard treatment since 2006.

Despite their effectiveness, there are ongoing questions about optimal treatment regimens, injection frequency, and safety, prompting research into new agents and delivery methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment for neovascular age related macular degeneration: The state of the art. Eandi, CM., Alovisi, C., De Sanctis, U., et al.[2017]

The phase IIb study of the Brimonidine Drug Delivery System (Gen 2) involving 310 patients with geographic atrophy (GA) showed that while the primary efficacy endpoint was not met at 24 months, there was a numeric trend indicating a 7% reduction in GA progression compared to sham treatment.

Brimo DDS was well tolerated with no significant safety concerns, and treatment-related adverse events were primarily linked to the injection procedure, indicating that the method of delivery is safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration. Freeman, WR., Bandello, F., Souied, E., et al.[2023]

Aflibercept, used in patients with exudative age-related macular degeneration who previously received other treatments, showed significant anatomical improvement, with a decrease in central subfoveal thickness from 300 to 275 µm at 1 month, maintained at 6 months.

Visual acuity remained stable after switching to aflibercept, indicating that while the treatment improved eye structure, it did not lead to significant changes in vision compared to baseline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial utilization of aflibercept in exudative age-related macular degeneration. Cho, H., Weber, ML., Shah, CP., et al.[2017]

The study demonstrated that a single intravitreous injection of AAV2-sFLT01 is safe and well tolerated in patients with advanced neovascular age-related macular degeneration, with only a few mild adverse events reported.

Among the patients treated, some showed significant improvements in vision and reduction of fluid in the eye, indicating potential efficacy, although further research is needed to understand variability in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreous injection of AAV2-sFLT01 in patients with advanced neovascular age-related macular degeneration: a phase 1, open-label trial. Heier, JS., Kherani, S., Desai, S., et al.[2022]

In a study of 60 patients receiving an average of 8.4 intravitreal injections of ziv-aflibercept over a mean follow-up of 9.2 months, significant improvements in best-corrected visual acuity (BCVA) and reductions in central macular thickness (CMT) were observed, indicating the treatment's efficacy for retinal disease.

The treatment was found to be safe, with no significant increases in intraocular pressure, no progression of lens opacities, and only one case of mild transient iritis, suggesting that repeated injections of ziv-aflibercept are well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of ziv-aflibercept in retinal diseases. Mansour, AM., Ashraf, M., Dedhia, CJ., et al.[2022]

Antibody-based therapies have significantly improved the treatment of wet age-related macular degeneration (AMD), with innovative approaches like port delivery systems and bispecific antibodies showing promise in clinical trials.

While stem cell and gene therapies are still under investigation for both wet and dry AMD, they present potential benefits and risks that need further evaluation before clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene, Cell and Antibody-Based Therapies for the Treatment of Age-Related Macular Degeneration. Akyol, E., Lotery, A.[2020]

In a phase 1 study involving 28 patients with neovascular age-related macular degeneration, a single intravitreal injection of aflibercept at 4 mg significantly reduced central retinal thickness and improved best corrected visual acuity compared to the 0.15 mg dose, particularly at weeks 4 and 6.

The higher 4 mg dose also resulted in fewer patients needing retreatment after 8 weeks, while maintaining a similar safety profile to the lower dose, with no serious adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of very high- and very low-dose intravitreal aflibercept in patients with neovascular age-related macular degeneration. Nguyen, QD., Campochiaro, PA., Shah, SM., et al.[2012]

Citations

1. ctv.veeva.com ctv.veeva.com/study/clinical-study-to-evaluate-the-safety-tolerability-and-preliminary-efficacy-of-intravitreal-ivt

Clinical Study to Evaluate the Safety, Tolerability, and ... This will be a clinical study to assess initial safety and tolerability of IVT ABI-110 in patients diagnosed with wet macular degeneration (wAMD) ...

2. withpower.com withpower.com/trial/phase-2-polypoidal-choroidal-vasculopathy-7-2024-a619b

ABI-110 for Wet Age-Related Macular Degeneration Among the patients treated, some showed significant improvements in vision and reduction of fluid in the eye, indicating potential efficacy, although further ...

3. clinconnect.io clinconnect.io/trials/NCT06550011

Clinical Study to Evaluate the Safety, Tolerability, and This will be a clinical study to assess initial safety and tolerability of IVT ABI-110 in patients diagnosed with wet macular degeneration (wAMD), ...

4. synapse.patsnap.com synapse.patsnap.com/drug/023e9e9c94f84602b9092c362b8fffcf

ABI-110 - Drug Targets, Indications, Patents The Phase 1 clinical trial is designed to evaluate the safety, tolerability, and preliminary efficacy of ABI-110 in patients with Wet AMD and PCV. About Avirmax ...

5. modernretina.com modernretina.com/view/first-patient-dosed-in-phase-i-iia-clinical-trial-of-abi-110

First patient dosed in phase I/IIa clinical trial of ABI-110 ABI-110 has the potential to offer a durable and effective solution by addressing the root causes of wet AMD at the genetic level.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01482910

NCT01482910 | VEGF Trap-Eye: Investigation of Efficacy ... This study will assess the efficacy and safety of intravitreally (IVT), i.e. directly into the eye administered VEGF Trap-Eye compared with ...