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

Trial Summary

What is the purpose of this trial?

This will be a clinical study to assess initial safety and tolerability of IVT ABI-110 in patients diagnosed with wet macular degeneration (wAMD), including symptomatic macular PCV.

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.

What data supports the effectiveness of the treatment ABI-110 for Wet Age-Related Macular Degeneration?

Research shows that injections of AAV2 vectors, which are part of ABI-110, can deliver proteins that block VEGF (a protein that causes vision problems) and help preserve vision in patients with age-related macular degeneration. ^{1 2 3 4 5}

What safety data exists for ABI-110 (AAV2.N54-VEGF Trap) in humans?

The safety of treatments similar to ABI-110, like aflibercept and AAV2-sFLT01, has been studied in people with eye conditions like wet age-related macular degeneration. These studies generally show that such treatments are safe for use in the eye, with some patients experiencing mild side effects like eye discomfort or increased eye pressure. ^{1 6 7 8 9}

How is the treatment ABI-110 different from other treatments for wet age-related macular degeneration?

ABI-110 is unique because it uses gene therapy to deliver a VEGF-neutralizing protein directly into the eye, potentially reducing the need for frequent injections that are common with other treatments. ^{1 10 11 12 13}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2022]

2. United States 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. [2021]

3. United States 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. [2009]

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

Evaluation of very high- and very low-dose intravitreal aflibercept in patients with neovascular age-related macular degeneration. [2012]

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

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

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

Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. [2022]

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

SUSTAINED BIWEEKLY AFLIBERCEPT FOR REFRACTORY NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The Prospective TRISTAR Study. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of ziv-aflibercept in retinal diseases. [2022]

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. New Zealand pubmed.ncbi.nlm.nih.gov

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

11. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment for neovascular age related macular degeneration: The state of the art. [2017]

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

Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration. [2023]

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

Initial utilization of aflibercept in exudative age-related macular degeneration. [2017]