A Phase 3 interventional study of Ixo-vec and Aflibercept in Neovascular Age-Related Macular Degeneration (nAMD) and Wet AMD, sponsored by Adverum Biotechnologies, Inc.. Recruiting at 79 sites in United States. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2026-09-24.
Sponsored by Adverum Biotechnologies, Inc. · Phase 3, Interventional, and Treatment
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 intravitreal aflibercept (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 as an average at Weeks 52 and 56.
Safety, tolerability, and efficacy will be evaluated throughout the study.
The primary objective of this study is to evaluate the non-inferiority in efficacy of a single IVT injection of Ixo-vec 6 x 10\^10 vector genome (vg)/eye compared to an active comparator. Non-inferiority will be evaluated using a pre-specified margin defined in the protocol.
Neovascular AMD is a degenerative ocular disease associated with the infiltration of abnormal blood vessels in the retina from the underlying choroid layer and is a leading cause of blindness in patients over 65 years of age. The abnormal angiogenic process in nAMD is stimulated and modulated by vascular endothelial growth factor (VEGF). Treatment of nAMD requires frequent IVT injections of VEGF inhibitors (anti-VEGF) administered every 4-16 weeks. Ixo-vec (also known as ADVM-022 or AAV.7m8-aflibercept) is an adeno-associated virus (AAV)-based gene therapy product being developed for the treatment of nAMD. 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 therapy in clinical practice.
Safety, tolerability, and efficacy will be evaluated throughout this study. The primary endpoint of this study is the mean change in BCVA of Ixo-vec compared to an active comparator measured as an average at Weeks 52 and 56 post-treatment.
Due to the long duration of the Screening period, this study will be considered fully enrolled when randomization has been completed.
Exclusion Criteria:
General Exclusion Criteria
History or evidence of any of the following cardiovascular diseases:
Ocular Exclusion Criteria
History or evidence of the following in the study eye:
Uncontrolled ocular hypertension or glaucoma in the study eye from Screening Visit 1 to Week 1 or current use of ≥ 2 intraocular pressure (IOP) lowering medications or normal tension glaucoma/suspect in the study eye or history of any of the following procedures in the study eye prior to Week 1:
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.
Genetic: Ixo-vec · Drug: Aflibercept
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.
Drug: Aflibercept
Ixo-vec will be administered intravitreally.
Aflibercept will be administered intravitreally.
Mean Change from Baseline in BCVA Based on an Average at Weeks 52 and 56
BCVA will be measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart.
Time frame: Baseline, Week 52 and Week 56
Mean Number of Aflibercept IVT Injections Received
Time frame: Week 4 through Week 56
Percentage of Participants with Worsened BCVA
BCVA measured by ETDRS.
Time frame: Through Week 56
Percentage of Participants with Improved BCVA
BCVA measured by ETDRS.
Time frame: Through Week 56
Mean Change from Baseline in BCVA Over Time Based on an Average at Weeks 52 and 56
BCVA measured by ETDRS.
Time frame: Baseline Through Week 56
Mean Change from Week 1 in BCVA Based on an Average at Weeks 52 and 56
BCVA measured by ETDRS.
Time frame: Week 1 through Week 56
Percentage of Participants with BCVA of 73 Letters or More from Week 4 Through Week 56
Time frame: Week 4 through Week 56
Mean Change in Central Subfield Thickness (CST) from Baseline Over Time Through Week 56
CST as measured by spectral domain optical coherence tomography (SD-OCT).
Time frame: Baseline Through Week 56
Percentage of Participants with CST ≤ 300 μm Over Time Through Week 56
CST will be assessed by a central reading center (CRC) using SD-OCT.
Time frame: Through Week 56
Mean Number of CST Fluctuations > 50 μm From Week 1 Over Time Through Week 56
CST will be assessed by a CRC using SD-OCT images and the mean number of fluctuations with thickness of more than 50 μm will be summarized.
Time frame: Week 1 through Week 56
Percentage of Participants with CST Fluctuations > 50 μm from Week 1 Over Time Through Week 56
CST will be assessed using SD-OCT.
Time frame: Week 1 through Week 56
Percent Reduction in Mean Rate of Annualized Anti-VEGF Injections
Percent reduction in mean rate of annualized anti-VEGF injections will be assessed relative to the reduction in mean rate of annualized anti-VEGF injections received in the year prior to screening in treatment-experienced participants.
Time frame: Through Week 56
Percentage of Participants Who Were Aflibercept Injection-free
Time frame: Week 4 through Week 56
Percentage of Participants Who Received 0 or 1 Aflibercept Injection
Time frame: Week 4 through Week 56
Mean Change in Area of Choroidal Neovascularization (CNV) Lesion from Baseline Over Time Through Week 56
CNV is the infiltration of abnormal blood vessels in the retina from the underlying choroid layer. It will be assessed by a CRC using SD-OCT.
Time frame: Baseline through Week 56
Mean Change in Macular Volume from Baseline Over Time Through Week 56
Macular volume will be measured as part of the full ophthalmic examination.
Time frame: Baseline through Week 56
Percentage of Participants Without Intraretinal Fluid (IRF) Over Time Through Week 56
IRF will be assessed using SD-OCT.
Time frame: Through Week 56
Percentage of Participants Without Subretinal Fluid (SRF) Over Time Through Week 56
SRF will be assessed using SD-OCT.
Time frame: Through Week 56
Percentage of Participants Without IRF and/or SRF Over Time Through Week 56
IRF and SRF will be assessed using SD-OCT.
Time frame: Through Week 56
Time to Dry Retina
Dry retina is defined as no IRF or SRF (i.e., absence of both). IRF and SRF will be assessed using SD-OCT.
Time frame: Through Week 56
Time to Sustained Dry Retina
Sustained dry retina is defined as no IRF or SRF (i.e., absence of both) maintained for 2 consecutive visits.
Time frame: Through Week 56
Number of Participants Who Experienced Ocular Adverse Events
The number of participants who experience an ocular adverse event will be summarized.
Time frame: Through Week 56
Number of Participants Who Experienced Mild, Moderate or Severe Ocular Adverse Events
The number of participants who experience a mild, moderate or severe ocular adverse event will be summarized.
Time frame: Through Week 56
Number of Participants Who Experienced Non-ocular Adverse Events
The number of participants who experience a non-ocular adverse event will be summarized.
Time frame: Through Week 56
Number of Participants Who Experienced Mild, Moderate or Severe Non-ocular Adverse Events
The number of participants who experience a mild, moderate or severe non-ocular adverse event will be summarized.
Time frame: Through Week 56
Mean Change in 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) Total and Subscale Scores
The NEI VFQ-25 measures vision-targeted patient-reported outcomes of individuals with chronic eye diseases. It comprises 25 questions. The assessment generates an overall composite score and includes the following subscales: global vision rating, difficulty with near vision activities, difficulty with distance vision activities, limitations in social functioning due to vision, role limitations due to vision, dependency on others due to vision, mental health symptoms due to vision, driving difficulties, limitations with peripheral and color vision, and ocular pain. A decrease in the NEI VFQ-25 score represents an improvement in disease severity.
Time frame: Day 1 to Week 28 and Week 56
Mean Change in the 5-item Health-related Quality of Life Questionnaire (EQ-5D-5L)
The EQ-5D-5L is a concise, generic self-reported health questionnaire which is weighted to reflect the relevant importance to patients of various different health problems. In retinal disease, the questionnaire is used to assess quality of life in the context of vision loss. It measures five parameters; mobility, self-care, usual activities, pain/discomfort and anxiety/depression. An increase in the EQ-5D-5L score represents an improvement in disease severity.
Time frame: Day 1 to Week 28 and Week 56
Plan to share: Yes — Adverum is committed to transparency. Appropriately de-identified participant-level data and supporting documents may be shared under appropriate conditions (e.g. when contractually permitted and when participants provide appropriate consent). Individual patient-level data would only be shared following completion of this study (and any associated studies), completion of applicable regulatory submissions, and in accordance with applicable regulations and laws, as well as criteria established by Adverum, our collaborators and/or industry best practices. Shared datasets and/or documents may be de-identified and/or redacted to protect participant identity and to protect sensitive and confidential information. For inquiries, please contact us at datasharing@adverum.com.
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Adverum Biotechnologies, Inc.