Neovascular Age-Related Macular Degeneration (nAMD)Phase 3AQUARIUSNCT07482176
Efficacy and Safety Study of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-related Macular Degeneration (AQUARIUS)
A Phase 3 study testing Ixo-vec and Aflibercept in people with Neovascular Age-Related Macular Degeneration (nAMD) and Wet AMD, run by Adverum Biotechnologies, Inc. at 79 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Neovascular Age-Related Macular Degeneration (nAMD), Wet AMD
- What is being tested?
- Ixo-vec and Aflibercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 534 participants
- Where
- 79 sitesUnited States
- Study dates
- 16 Mar 2026to 20 Oct 2031
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able and willing to provide informed consent (or have a legally authorized representative who is able and willing to provide informed consent) prior to any study assessments and procedures and comply with the study requirements and visits.
- Male or female with a diagnosis of CNV secondary to nAMD in the study eye, with nAMD disease activity at Screening Visit 1.
- At least 50 years old at Screening Visit 1.
- An ETDRS BCVA letter score of 35 - 78 (approximate Snellen equivalent of 20/200 to 20/32) in the study eye at Screening Visit 1.
- Demonstrated a meaningful anatomic response to anti-VEGF therapy during screening.
- Able to reliably use eye drops per protocol.
Who cannot join
- General Exclusion Criteria
- History of a medical condition giving reasonable suspicion of a condition that contraindicates the use of Ixo-vec, compromises the participant's ability to comply with the planned study activities, or that might affect the interpretation of the results of the study or render the participant at high risk for treatment complications in the opinion of the Investigator. History of severe coronavirus disease (COVID-19) infection may meet this exclusion criterion if, in the opinion of the Investigator, it is likely to lead to any important complications.
- Received any prior gene therapy.
- Prior treatment with any non-gene therapy investigational medicinal product (IMP) or medical device in the study eye within 3 months of Screening Visit 1 or 5 half-lives of the IMP prior to dosing with Ixo-vec, whichever is longer.
- Female participants who are pregnant or breastfeeding or who intend to become pregnant or breastfeed in the future.
- History or evidence of any of the following cardiovascular diseases:
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- Myocardial infarction in the 6-month period prior to Week 1.
- Uncontrolled hypertension defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg during screening.
- Stroke in the 6-month period prior to Week 1.
- History of ongoing bleeding disorders. The use of aspirin or other anticoagulants (e.g., Factor Xa inhibitors) is permitted.
- Use of systemic immunosuppressive drugs within 90 days prior to Screening Visit 1. Short courses of oral corticosteroids are permitted, as well as any inhaled, intra-articular, nasal or dermal steroid use.
- Evidence of poorly controlled diabetes or glycated hemoglobin (HbA1c) ≥ 8.0% during screening.
- Ocular Exclusion Criteria
- Any active ocular or periocular infection in the study eye from Screening Visit 1.
- History or evidence of the following in the study eye:
- Intraocular or refractive surgery within 5 months prior to Week 1.
- Any previous penetrating keratoplasty or vitrectomy.
- Any previous panretinal photocoagulation.
- Any previous submacular surgery, other surgical intervention (including port delivery system) or laser treatment for age-related macular degeneration.
- Any history or evidence of retinal detachment (with or without repair) or retinal pigment epithelium rip/tear in the study eye, as determined by the Investigator during screening or at Week 1.
- 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:
- Incisional glaucoma surgery (i.e., glaucoma drainage implant/shunt or trabeculectomy)
- Ocular angle-based surgery (i.e., goniotomy or canaloplasty)
- Minimally Invasive Glaucoma Surgery (MIGS) in the study eye.
- Angle-based glaucoma surgery (e.g., Argon or Selective Laser Trabeculoplasty)
- Any history of IOP elevation related to topical steroid administration in either eye.
- Any history of uveitis or inflammation (grade trace or above) except mild anticipated post operative inflammation that resolved in either eye.
- Any history of treatment with complement inhibitors for geographic atrophy in the study eye.
- Known history of ocular herpes simplex virus, varicella-zoster virus, or cytomegalovirus, including viral uveitis, retinitis, or keratitis in either eye.
Trial locations and contacts
79 sites in 1 country. Contact the study team or a site near you to ask about taking part.
79 sites in 1 country
United States79 sites, 79 recruiting
- Recruiting
Adverum Clinical Site 145
Arlington, Texas, 76012
- Recruiting
Adverum Clinical Site 196
Asheville, North Carolina, 28803
- Recruiting
Adverum Clinical Site 182
Augusta, Georgia, 30909
- Recruiting
Adverum Clinical Site 127
Austin, Texas, 78705
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Adverum Clinical Site 243
Austin, Texas, 78750
- Recruiting
Adverum Clinical Site 109
Bakersfield, California, 93309
- Recruiting
Adverum Clinical Site 248
Beachwood, Ohio, 44122-5846
- Recruiting
Adverum Clinical Site 100
Beverly Hills, California, 90211
- Recruiting
Adverum Clinical Site 240
Bloomfield, New Jersey, 07003
- Recruiting
Adverum Clinical Site 241
Bluffton, South Carolina, 29910
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Adverum Clinical Site 201
Campbell, California, 95008
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Adverum Clinical Site 195
Carmel, Indiana, 46032
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Adverum Clinical Site 205
Carmel, Indiana, 46032
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Adverum Clinical Site 253
Carmel, Indiana, 46032
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Adverum Clinical Site 234
Cary, North Carolina, 27511
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Adverum Clinical Site 246
Chicago, Illinois, 60616
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Adverum Clinical Site 247
Cleveland, Ohio, 44130
- Recruiting
Adverum Clinical Site 107
Conroe, Texas, 77384
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Adverum Clinical Site 194
Dallas, Texas, 75231
- Recruiting
Adverum Clinical Site 124
Deerfield Beach, Florida, 33064
- Recruiting
Adverum Clinical Site 184
Deerfield Beach, Florida, 33064
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Adverum Clinical Site 200
Denver, Colorado, 800222
- Recruiting
Adverum Clinical Site 116
Denver, Colorado, 80207
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Adverum Clinical Site 254
Edmond, Oklahoma, 73013
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Adverum Clinical Site 172
Encino, California, 91436
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Adverum Clinical Site 181
Erie, Pennsylvania, 16505
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Adverum Clinical Site 176
Fort Lauderdale, Florida, 33308
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Adverum Clinical Site 221
Fort Myers, Florida, 33912
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Adverum Clinical Site 169
Fullerton, California, 92835
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Adverum Clinical Site 236
Gainesville, Florida, 32607
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Adverum Clinical Site 211
Greensboro, North Carolina, 27401
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Adverum Clinical Site 219
Greensboro, North Carolina, 27401
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Adverum Clinical Site 197
Hagerstown, Maryland, 21740
- Recruiting
Adverum Clinical Site 204
Hagerstown, Maryland, 21740
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Adverum Clinical Site 220
Hickory, North Carolina, 28602
- Recruiting
Adverum Clinical Site 224
Huntington Beach, California, 92647
- Recruiting
Adverum Clinical Site 216
Jackson, Mississippi, 39202
- Recruiting
Adverum Clinical Site 222
Ladson, South Carolina, 29456
- Recruiting
Adverum Clinical Site 214
Lakeland, Florida, 33805
- Recruiting
Adverum Clinical Site 225
Liverpool, New York, 13088
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Adverum Clinical Site 199
Lynchburg, Virginia, 24502
- Recruiting
Adverum Clinical Site 162
McAllen, Texas, 78503
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Adverum Clinical Site 245
Mesa, Arizona, 85206
- Recruiting
Adverum Clinical Site 168
Miami Springs, Florida, 33166
- Recruiting
Adverum Clinical Site 101
Nashville, Tennessee, 37203
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Adverum Clinical Site 179
Oak Forest, Illinois, 60452
- Recruiting
Adverum Clinical Site 207
Oak Park, Illinois, 60304
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Adverum Clinical Site 213
Orlando, Florida, 32806
- Recruiting
Adverum Clinical Site 239
Philadelphia, Pennsylvania, 19102
- Recruiting
Adverum Clinical Site 110
Philadelphia, Pennsylvania, 19107
- Recruiting
Adverum Clinical Site 126
Phoenix, Arizona, 85014
- Recruiting
Adverum Clinical Site 178
Phoenix, Arizona, 85020
- Recruiting
Adverum Clinical Site 223
Phoenix, Arizona, 85020
- Recruiting
Adverum Clinical Site 206
Plantation, Florida, 33324
- Recruiting
Adverum Clinical Site 252
Portland, Oregon, 97225
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Adverum Clinical Site 130
Poway, California, 92064
- Recruiting
Adverum Clinical Site 215
Redlands, California, 92374
- Recruiting
Adverum Clinical Site 244
Rochester, New York, 14620
- Recruiting
Adverum Clinical Site 140
Sacramento, California, 95825
- Recruiting
Adverum Clinical Site 212
Sacramento, California, 95841
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Adverum Clinical Site 185
San Antonio, Texas, 78240
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Adverum Clinical Site 232
San Marcos, Texas, 78666
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Adverum Clinical Site 175
Santa Barbara, California, 93103
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Adverum Clinical Site 228
Schertz, Texas, 78154
- Recruiting
Adverum Clinical Site 229
Scottsdale, Arizona, 85255
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Adverum Clinical Site 249
Silverdale, Washington, 98383
- Recruiting
Adverum Clinical Site 183
South Miami, Florida, 33143
- Recruiting
Adverum Clinical Site 198
Springdale, Arkansas, 72764
- Recruiting
Adverum Clinical Site 120
St. Petersburg, Florida, 33711
- Recruiting
Adverum Clinical Site 242
Sun City, Arizona, 85351
- Recruiting
Adverum Clinical Site 148
Tampa, Florida, 33609
- Recruiting
Adverum Clinical Site 171
Teaneck, New Jersey, 07666
- Recruiting
Adverum Clinical Site 231
The Woodlands, Texas, 77384
- Recruiting
Adverum Clinical Site 202
Torrance, California, 90503
- Recruiting
Adverum Clinical Site 237
Tyler, Texas, 75703
- Recruiting
Adverum Clinical Site 209
Wake Forest, North Carolina, 27587
- Recruiting
Adverum Clinical Site 189
Walnut Creek, California, 94598
- Recruiting
Adverum Clinical Site 165
Waterford, Connecticut, 06385
- Recruiting
Adverum Clinical Site 238
Winter Haven, Florida, 33880
About this study
Official title: A Multi-center, Randomized, Double-masked, Active-comparator-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-related Macular Degeneration (AQUARIUS)
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.
Read the detailed description
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.
- Being tested
- Ixo-vec, Aflibercept
- Keywords
- Ixoberogene soroparvovec, Ixo-vec, Aflibercept, Neovascular age-related macular degeneration, nAMD, ADVM, ADVM-022, Wet AMD, wAMD, Wet Age-related Macular Degeneration, CNV, Neovascular AMD, AAV, AAV vector, AAV.7m8-aflibercept, AAV.7m8, Gene therapy, Eye disease, Blindness, Adeno-associated viruses
- Medical subject headings
- Eye Diseases, Blindness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ixo-vecGenetic
Ixo-vec will be administered intravitreally.
AfliberceptDrug
Aflibercept will be administered intravitreally.
| Study group | Role | What they receive |
|---|---|---|
| Ixo-vec | Experimental | 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. Receives: Genetic: Ixo-vec; Drug: Aflibercept |
| Aflibercept | Active comparator | 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. Receives: Drug: Aflibercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 52 and Week 56
Secondary outcomes (26)
Mean Number of Aflibercept IVT Injections Received
Measured: Week 4 through Week 56
Percentage of Participants with Worsened BCVA
BCVA measured by ETDRS.
Measured: Through Week 56
Percentage of Participants with Improved BCVA
BCVA measured by ETDRS.
Measured: Through Week 56
Mean Change from Baseline in BCVA Over Time Based on an Average at Weeks 52 and 56
BCVA measured by ETDRS.
Measured: Baseline Through Week 56
Mean Change from Week 1 in BCVA Based on an Average at Weeks 52 and 56
BCVA measured by ETDRS.
Measured: Week 1 through Week 56
Percentage of Participants with BCVA of 73 Letters or More from Week 4 Through Week 56
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Through Week 56
Percentage of Participants Who Were Aflibercept Injection-free
Measured: Week 4 through Week 56
Percentage of Participants Who Received 0 or 1 Aflibercept Injection
Measured: 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.
Measured: 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.
Measured: Baseline through Week 56
Percentage of Participants Without Intraretinal Fluid (IRF) Over Time Through Week 56
IRF will be assessed using SD-OCT.
Measured: Through Week 56
Percentage of Participants Without Subretinal Fluid (SRF) Over Time Through Week 56
SRF will be assessed using SD-OCT.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Through Week 56
Number of Participants Who Experienced Ocular Adverse Events
The number of participants who experience an ocular adverse event will be summarized.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 to Week 28 and Week 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2026
- Study start16 Mar 2026
- Primary completion15 Nov 2027 (estimated)
- Study completion20 Oct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neovascular Age-Related Macular Degeneration (nAMD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 534 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Adverum Biotechnologies, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Adam Turpcu, PhD, Study director, Adverum Biotechnologies, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07482176
- Sponsor's protocol ID
- ADVM-022-13
- Acronym
- AQUARIUS
- Status last verified
- Sep 2026
- First submitted
- 16 Mar 2026
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.