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Ixo-vec gene therapy versus aflibercept for wet age-related macular degeneration (AQUARIUS)

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)

Phase 3 Interventional Adverum Biotechnologies, Inc. · NCT07482176

This study tests whether a single injection of Ixo-vec gene therapy can maintain or improve vision as well as regular aflibercept injections in adults aged 50 and older with active neovascular (wet) AMD.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment284 (estimated)
Ages50 Years and up
SexAll
SponsorAdverum Biotechnologies, Inc. Industry-sponsored
Locations36 sites (Phoenix, Arizona and 35 other locations)
Trial IDNCT07482176 on ClinicalTrials.gov

What this trial studies

AQUARIUS is a randomized, double-masked, active-comparator Phase 3 trial that compares a single intravitreal injection of Ixo-vec (6 x 10^10 vector genomes per eye) to intravitreal aflibercept. The primary goal is to show non-inferiority for mean change in best corrected visual acuity, measured as the average at Weeks 52 and 56. The trial enrolls a broad nAMD population (including treatment-naïve and treatment-experienced participants) with protocol-specified anatomic response criteria during screening. Safety, tolerability, and efficacy are followed throughout the study period.

Who should consider this trial

Good fit: Adults aged 50 or older with active choroidal neovascularization from nAMD, baseline BCVA roughly 35–78 ETDRS letters, ability to use eye drops, and who demonstrate a meaningful anatomic response to anti-VEGF during screening.

Not a fit: Patients with vision outside the eligible BCVA range, no anatomic response to prior anti-VEGF therapy, medical contraindications to intravitreal gene therapy, or who cannot attend the Phoenix, Arizona study visits are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, Ixo-vec could markedly reduce the need for frequent anti-VEGF injections and maintain vision with a single gene therapy injection.

How similar studies have performed: Early-phase trials of AAV-based aflibercept delivery (ADVM-022/Ixo-vec) have shown promising durability and safety signals, but large randomized phase 3 confirmation is still novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. 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.
2. Male or female with a diagnosis of CNV secondary to nAMD in the study eye, with nAMD disease activity at Screening Visit 1.
3. At least 50 years old at Screening Visit 1.
4. 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.
5. Demonstrated a meaningful anatomic response to anti-VEGF therapy during screening.
6. Able to reliably use eye drops per protocol.

Exclusion Criteria:

General Exclusion Criteria

1. 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.
2. Received any prior gene therapy.
3. 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.
4. Female participants who are pregnant or breastfeeding or who intend to become pregnant or breastfeed in the future.
5. History or evidence of any of the following cardiovascular diseases:

   1. Myocardial infarction in the 6-month period prior to Week 1.
   2. Uncontrolled hypertension defined as systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg during screening.
   3. Stroke in the 6-month period prior to Week 1.
6. History of ongoing bleeding disorders. The use of aspirin or other anticoagulants (e.g., Factor Xa inhibitors) is permitted.
7. 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.
8. Evidence of poorly controlled diabetes or glycated hemoglobin (HbA1c) ≥ 8.0% during screening.

Ocular Exclusion Criteria

1. Any active ocular or periocular infection in the study eye from Screening Visit 1.
2. History or evidence of the following in the study eye:

   1. Intraocular or refractive surgery within 5 months prior to Week 1.
   2. Any previous penetrating keratoplasty or vitrectomy.
   3. Any previous panretinal photocoagulation.
   4. Any previous submacular surgery, other surgical intervention (including port delivery system) or laser treatment for age-related macular degeneration.
3. 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.
4. 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:

   1. Incisional glaucoma surgery (i.e., glaucoma drainage implant/shunt or trabeculectomy)
   2. Ocular angle-based surgery (i.e., goniotomy or canaloplasty)
   3. Minimally Invasive Glaucoma Surgery (MIGS) in the study eye.
   4. Angle-based glaucoma surgery (e.g., Argon or Selective Laser Trabeculoplasty)
5. Any history of IOP elevation related to topical steroid administration in either eye.
6. Any history of uveitis or inflammation (grade trace or above) except mild anticipated post operative inflammation that resolved in either eye.
7. Any history of treatment with complement inhibitors for geographic atrophy in the study eye.
8. Known history of ocular herpes simplex virus, varicella-zoster virus, or cytomegalovirus, including viral uveitis, retinitis, or keratitis in either eye.

Where this trial is running

Phoenix, Arizona and 35 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Neovascular Age-Related Macular DegenerationWet AMDIxoberogene soroparvovecIxo-vecAfliberceptNeovascular age-related macular degenerationnAMDADVM
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.