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.. Active, not recruiting at 75 sites in United States. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2026-05-22.
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 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.
The primary objective of this study is to evaluate the non-inferiority in efficacy of a single intravitreal (IVT) injection of Ixo-vec 6 x 10\^10 vector genome (vg)/eye compared to an active comparator.
Neovascular or wet age-related macular degeneration (nAMD) 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 intravitreal (IVT) injections of VEGF inhibitors (anti-VEGF) administered every 4-16 weeks. Ixo-vec (also known as ADVM-022 or AAV.7m8-aflibercept) is a 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. This study will be considered fully enrolled when randomization has been completed.
Safety, tolerability, and efficacy will be evaluated throughout this study. 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 post-treatment.
After completing the Week 56 visit, participants will continue in the long-term follow-up period for 4 additional years (a total of 5 years on study).
388 studies on the registry are indexed under Eye Diseases; 62 are open to participants now.
This study's enrollment of 311 is above the median of 62 across 269 interventional studies indexed under Eye Diseases.
Browse Eye Diseases studies →Adverum Biotechnologies, Inc. is the lead sponsor of 11 studies on the registry; 2 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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 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:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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 Best-Corrected Visual Acuity (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 from Baseline through Week 56 and Week 104
BCVA measured by ETDRS
Time frame: Baseline through Week 56 and Week 104
Percentage of participants with improved BCVA from Baseline through Week 56 and Week 104
BCVA measured by ETDRS
Time frame: Baseline through Week 56 and Week 104
Mean change from Baseline in BCVA through Week 104
BCVA measured by ETDRS
Time frame: Baseline through Week 104
Mean change from Week 1 in BCVA based on an average at Weeks 52 and 56 and at Week 104
BCVA measured by ETDRS
Time frame: Week 1 to Week 56 and Week 104
Percentage of participants with BCVA of 73 letters or more from Week 4 through Week 56 and Week 104
Time frame: Week 4 through Week 56 and Week 104
Mean change in Central Subfield Thickness (CST) from Baseline to Week 56 and Week 104
CST as measured by spectral domain optical coherence tomography (SD-OCT)
Time frame: Baseline to Week 56 and Week 104
Percentage of participants with CST ≤ 300 μm at Week 56 and Week 104
CST will be assessed by a CRC using SD-OCT
Time frame: Week 56 and Week 104
Mean number of CST fluctuations > 50 μm from Week 1 through Week 56 and Week 104
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 and Week 104
Percentage of participants with CST fluctuations > 50 μm from Week 1 through Week 56 and Week 104
CST will be assessed using SD-OCT
Time frame: Week 1 through Week 56 and Week 104
Mean number of aflibercept IVT injections received from Week 4 through Week 104
Time frame: Week 4 through Week 104
Percent reduction in mean rate of annualized anti-Vascular Endothelial Growth Factor (VEGF) injections after 56 weeks and 104 weeks of study treatment.
Percent reduction in mean rate of annualized anti-VEGF injections will be assessed (after 56 weeks and after 104 weeks of study treatment) 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: Week 56 and Week 104
Percentage of participants who were aflibercept injection-free
Time frame: Week 4 through Week 56 and through Week 104
Percentage of participants who received 0 or 1 aflibercept injection
Time frame: Week 4 through Week 56 and through Week 104
Percentage of participants who receive 0, 1, or 2 aflibercept injections from Week 4 through Week 56 and through Week 104
Time frame: Week 4 through Week 56 and through Week 104
Mean change in area of Choroidal Neovascularization (CNV) lesion from Baseline through Week 104
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 104
Mean change in macular volume from Baseline through Week 104
Macular volume will be measured as part of the full ophthalmic examination.
Time frame: Baseline through Week 104
Percentage of participants without Intraretinal Fluid (IRF) through Week 104
IRF will be assessed using SD-OCT
Time frame: Through Week 104
Percentage of participants without Subretinal Fluid (SRF) through Week 104
SRF will be assessed using SD-OCT
Time frame: Through Week 104
Percentage of participants with dry retina (defined as no IRF or SRF) through Week 104
Dry Retina will be assessed using SD-OCT
Time frame: Through Week 104
Time to dry retina
Dry retina is defined as no IRF or SRF (i.e., absence of both) and will be assessed using SD-OCT
Time frame: Through Week 104
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 104
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 and Week 104
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 and Week 104
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 and Week 104
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 and Week 104
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, Week 56, and Week 104
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 the identity of participants and to protect sensitive and confidential information. For inquiries, please contact us at datasharing@adverum.com.
No publications or documents are linked to this record.
Started Feb 2025 (actual). Primary completion is estimated for Dec 2026, 21 months after the start.
Of 28 phase 3 interventional studies under Eye Diseases, half reached primary completion within 25 months of starting (the median), counting those still running; a quarter within 20 and three quarters within 39. This study's planned 21 months is below that.
Eye Diseases covers many different conditions, not one, so the studies compared here vary widely. Read these figures as a rough guide.
How these figures are worked out, and which studies are left out of them.
This study is active, not recruiting, as verified in May 2026. You cannot join it, but the record below documents what was studied.
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Adverum Biotechnologies, Inc.