Ixo-vec + Aflibercept for Age-Related Macular Degeneration

(ARTEMIS Trial)

Recruiting at 49 trial locations

Overseen By Adverum Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Adverum Biotechnologies, Inc.

Must be taking: Anti-VEGF therapy

Must not be taking: Systemic immunosuppressive drugs

Disqualifiers: Pregnancy, Uncontrolled hypertension, Diabetes, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 56 weeks

284 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for wet age-related macular degeneration (nAMD), a condition that affects vision. Researchers compare a single injection of a new drug, Ixo-vec (Ixoberogene Soroparvovec, a gene therapy), to a standard treatment called Aflibercept. The goal is to determine which treatment improves vision more effectively over time. Individuals diagnosed with active nAMD who have responded well to anti-VEGF treatments might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you have used systemic immunosuppressive drugs within 90 days before the screening.

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

Research has shown that Ixo-vec is generally well-tolerated by patients with neovascular age-related macular degeneration (nAMD). In previous studies, Ixo-vec helped maintain vision and showed promise in reducing the need for frequent anti-VEGF injections, common treatments for nAMD. Over four years, patients reported that Ixo-vec did not cause serious side effects for most people.

While specific side effects weren't detailed, the long-term use and positive feedback suggest that Ixo-vec is relatively safe. As with any treatment, some people might experience different reactions, but overall, evidence supports that Ixo-vec is a well-tolerated option for managing nAMD. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for age-related macular degeneration?

Researchers are excited about Ixoberogene Soroparvovec (Ixo-vec) for age-related macular degeneration because it offers a novel approach compared to current treatments like anti-VEGF injections. Unlike standard therapies that require frequent injections, Ixo-vec involves a single gene therapy injection designed to provide long-lasting effects. This treatment utilizes a viral vector to deliver genes directly to the eye, potentially reducing the need for repeated treatments. By targeting the underlying causes of the disease, Ixo-vec aims to maintain vision with fewer interventions, a significant advancement over existing options.

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

Research has shown that Ixoberogene Soroparvovec (Ixo-vec), which participants in this trial may receive, might help treat wet age-related macular degeneration (nAMD). One study found that Ixo-vec helped maintain stable vision and improved eye health in people with nAMD. It also reduced the need for frequent anti-VEGF injections, commonly used to treat this condition. Most patients tolerated Ixo-vec well, and it demonstrated good results over several years. The evidence suggests that Ixo-vec could be a promising option for reducing the treatment burden and maintaining vision in nAMD patients. ^{1 2 3 5 6}

Who Is on the Research Team?

Adam Turpcu, PhD

Principal Investigator

Adverum Biotechnologies, Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 50 with neovascular age-related macular degeneration (nAMD) who have had some response to anti-VEGF therapy. Participants must be able to use eye drops and have a vision score of approximately 20/200 to 20/32 in the study eye.

Inclusion Criteria

Has your doctor said your AMD does NOT include large scarring or bleeding under the central vision area?

Exclusion Criteria

Do you have other serious eye diseases (e.g., diabetic retinopathy, uncontrolled glaucoma) in the study eye?

Have you had an eye injection (Eylea, Lucentis, Avastin, Vabysmo, Syfovre, Izervay, etc.) in the last 8 weeks?

Do you have an upcoming cataract surgery in the affected eye?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravitreal injection of Ixo-vec and comparator treatments

56 weeks

Monthly visits for injections and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aflibercept
• Ixoberogene Soroparvovec (Ixo-vec)

Trial Overview The study compares a single injection of Ixo-vec, a new treatment, against Aflibercept, an existing treatment for nAMD. It's randomized and double-masked, meaning neither participants nor researchers know who gets which treatment. The main goal is improving visual acuity after one year.

How Is the Trial Designed?

Group I: Ixo-vec Experimental Treatment 2 Interventions

Participants will receive 3 monthly loading doses of aflibercept 2 mg IVT, a single IVT injection of Ixo-vec 6 x 10\^10 vg/eye at Week 1, and sham injections every 8 weeks

Group II: Aflibercept Active Control 1 Intervention

Participants will receive 3 monthly loading doses of aflibercept 2 mg IVT, a sham injection at Week 1, and aflibercept 2 mg IVT every 8 weeks.

Who Is Running the Clinical Trial?

Adverum Biotechnologies, Inc.

Lead Sponsor

Trials

10

Recruited

560+

Published Research Related to This Trial

In a study of 16 eyes from 14 patients with neovascular age-related macular degeneration (nAMD) who did not respond to previous treatments, switching to intravitreal ziv-aflibercept (IVZ) therapy resulted in a longer treatment-free interval, averaging 114.4 days compared to 76.3 days before the switch.

Despite the increased treatment-free interval, there was no significant improvement in best corrected visual acuity (BCVA) or other anatomical measures after 12 months of IVZ therapy, with 50% of eyes experiencing a decline in vision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year outcome of intravitreal ziv-aflibercept therapy for non-responsive neovascular age-related macular degeneration. Braimah, IZ., Agarwal, K., Mansour, A., et al.[2018]

Intravitreal injections of aflibercept using a treat-and-extend regimen significantly improved best-corrected visual acuity (BCVA) in most subtypes of neovascular age-related macular degeneration (AMD) over a 2-year follow-up, except for retinal angiomatous proliferation (RAP).

While central macular thickness and central choroidal thickness decreased significantly, macular atrophy increased, particularly in RAP, where it correlated negatively with choroidal thickness, suggesting that treatment may inadvertently accelerate macular atrophy in this subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treat-and-Extend Regimen with Aflibercept for Neovascular Age-Related Macular Degeneration: Efficacy and Macular Atrophy Development. Matsumoto, H., Morimoto, M., Mimura, K., et al.[2019]

A study involving 12 patients showed that a single intravitreal injection of ziv-aflibercept for treating choroidal neovascularization due to age-related macular degeneration was safe, with no serious ocular or systemic adverse events reported after 30 days.

While there was only a slight improvement in best-corrected visual acuity after treatment, the absence of significant side effects suggests that ziv-aflibercept could be a viable low-cost alternative for macular disease therapy, especially in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT. Chhablani, J., Narayanan, R., Mathai, A., et al.[2022]

In a study of 32 treatment-naïve patients with neovascular age-related macular degeneration (nvAMD), aflibercept significantly improved best-corrected visual acuity after 13 months, with 46.8% of patients gaining at least 15 letters on the ETDRS scale.

Aflibercept treatment also led to a significant reduction in central macular thickness and was well tolerated, with no adverse events reported, indicating its safety and efficacy in a real-life clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aflibercept as First-Line Therapy in Patients with Treatment-Naïve Neovascular Age-Related Macular Degeneration: Prospective Case Series Analysis in Real-Life Clinical Practice. Udaondo, P., Salom, D., García-Delpech, S., et al.[2017]

In a study of 213 patients with treatment-naive neovascular age-related macular degeneration (nvAMD), the treat-and-extend regimen of intravitreal aflibercept led to a significant improvement in best corrected visual acuity (BCVA) after 12 months, with an average gain of 0.20 logMAR units (p < 0.001).

The treatment also resulted in substantial anatomical improvements, including a decrease in central retinal thickness from 347 µm to 246 µm (p < 0.001) and a reduction in the presence of subretinal and intraretinal fluid, indicating effective resolution of exudation in about half of the cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Visual and anatomical outcomes associated with treat-and-extend administration of intravitreal aflibercept for neovascular age-related macular degeneration. Soliman, MK., Tuli, N., Lee, TK., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06856577

NCT06856577 | Efficacy and Safety Study of Ixoberogene ... Ixo-vec is designed to reduce the current treatment burden which often results in undertreatment and vision loss in patients with nAMD receiving anti-VEGF ...

2. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00571-0/fulltext

Safety and efficacy of ixoberogene soroparvovec in ... Safety and efficacy of ixoberogene soroparvovec in neovascular age-related macular degeneration in the United States (OPTIC): a prospective ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38152412/

a prospective, two-year, multicentre phase 1 study Ixo-vec was generally well-tolerated, maintained vision, and improved anatomical outcomes in nAMD, with a substantial reduction in anti-VEGF injections.

4. investors.adverum.com investors.adverum.com/press_releases/news-details/2025/Adverum-Biotechnologies-Initiates-ARTEMIS-Phase-3-Study-Evaluating-Ixo-vecfor-Wet-AMD/default.aspx

Adverum Biotechnologies Initiates ARTEMIS Phase 3 ... This pivotal trial is designed to evaluate the efficacy and safety of Ixo-vec (ixoberogene soroparvovec) as a one-time intravitreal (IVT) ...

5. iovs.arvojournals.org iovs.arvojournals.org/article.aspx?articleid=2808869

Ixoberogene Soroparvovec (Ixo-vec) Intravitreal Gene ... - IOVS Ixo-vec was well tolerated through 4 years, preserved vision, and meaningfully reduced injection burden in patients with nAMD who previously needed frequent ...

6. investors.adverum.com investors.adverum.com/press_releases/news-details/2024/Adverum-Biotechnologies-Announces-Positive-Preliminary-Efficacy-and-Safety-Data-from-LUNA-Phase-2-Trial-of-Ixo-vec-in-Patients-with-Wet-AMD/default.aspx

Adverum Biotechnologies Announces Positive Preliminary ... Adverum Biotechnologies Announces Positive Preliminary Efficacy and Safety Data from LUNA Phase 2 Trial of Ixo-vec in Patients with Wet AMD.