Ixo-vec + Aflibercept for Age-Related Macular Degeneration

(ARTEMIS Trial)

Recruiting at 31 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

Trial Summary

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.

What data supports the effectiveness of the drug Ixo-vec + Aflibercept for age-related macular degeneration?

Research shows that aflibercept, one of the drugs in the treatment, is effective in improving vision and eye health in patients with age-related macular degeneration when used regularly over a year. ^{1 2 3 4 5}

Is the treatment with Ixo-vec and Aflibercept safe for humans?

Research on ziv-aflibercept, a similar treatment, shows it has been evaluated for safety in treating age-related macular degeneration, with studies analyzing its safety over periods ranging from 6 months to 1 year. ^{4 6 7 8 9}

How is the drug Ixo-vec + Aflibercept different from other treatments for age-related macular degeneration?

Ixo-vec (Ixoberogene Soroparvovec) combined with Aflibercept is unique because it potentially offers a gene therapy approach, which may provide longer-lasting effects compared to the regular bimonthly injections of Aflibercept alone, which are commonly used to manage age-related macular degeneration. ^{1 2 4 10 11}

What is the purpose of this trial?

This is a multi-center, randomized, double-masked, active-comparator-controlled, Phase 3 study in a broad participant population (treatment-naïve and treatment-experienced) with neovascular (wet) age-related macular degeneration (nAMD). The study will evaluate a single intravitreal (IVT) injection of Ixo-vec compared to an active comparator. The primary endpoint of this study is the mean change in best corrected visual acuity (BCVA) of Ixo-vec compared to an active comparator measured at an average of Weeks 52 and 56. Safety, tolerability, and efficacy will be evaluated throughout the study.

Research Team

Adam Turpcu, PhD

Principal Investigator

Adverum Biotechnologies, Inc.

Eligibility Criteria

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

I can use eye drops as instructed.

My vision in the study eye ranges from 20/200 to 20/32.

I can give my consent or have someone who can legally consent for me.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Aqueous vascular endothelial growth factor and aflibercept concentrations after bimonthly intravitreal injections of aflibercept for age-related macular degeneration. [2019]

2. Spain pubmed.ncbi.nlm.nih.gov

Outcomes in patients receiving fixed-dosed aflibercept for treatment-naïve neovascular age-related macular degeneration during one year of routine clinical practice. [2021]

3. Switzerland 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. [2017]

4. England pubmed.ncbi.nlm.nih.gov

One-year outcome of intravitreal ziv-aflibercept therapy for non-responsive neovascular age-related macular degeneration. [2018]

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

A single-arm, investigator-initiated study of the efficacy, safety, and tolerability of intravitreal aflibercept injection in subjects with exudative age-related macular degeneration previously treated with ranibizumab or bevacizumab (ASSESS study): 12-month analysis. [2022]

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

CLINICAL AND ELECTROPHYSIOLOGICAL EVALUATION AFTER INTRAVITREAL ZIV-AFLIBERCEPT FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety of 5914 intravitreal ziv-aflibercept injections. [2019]

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

INTRAVITREAL ZIV-AFLIBERCEPT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: 52-Week Results. [2020]

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

SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Visual and anatomical outcomes associated with treat-and-extend administration of intravitreal aflibercept for neovascular age-related macular degeneration. [2021]

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

Treat-and-Extend Regimen with Aflibercept for Neovascular Age-Related Macular Degeneration: Efficacy and Macular Atrophy Development. [2019]