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NCT07482176PHASE3Recruiting

Efficacy and Safety Study of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-related Macular Degeneration (AQUARIUS)

Adverum Biotechnologies, Inc.

Start Date

3/16/2026

Completion Date

10/20/2031

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). 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.

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.

Eligibility Criteria

Age Range: 50 years to No maximum

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.

Interventions

GENETIC

Ixo-vec

DRUG

Aflibercept

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Conditions

Neovascular Age-Related Macular Degeneration (nAMD)Wet AMD

Locations

Adverum Clinical Site 245

Mesa, Arizona 85206

United States

Adverum Clinical Site 126

Phoenix, Arizona 85014

United States

Adverum Clinical Site 178

Phoenix, Arizona 85020

United States

Adverum Clinical Site 223

Phoenix, Arizona 85020

United States

Adverum Clinical Site 229

Scottsdale, Arizona 85255

United States

Adverum Clinical Site 242

Sun City, Arizona 85351

United States

Adverum Clinical Site 198

Springdale, Arkansas 72764

United States

Adverum Clinical Site 109

Bakersfield, California 93309

United States

Adverum Clinical Site 100

Beverly Hills, California 90211

United States

Adverum Clinical Site 201

Campbell, California 95008

United States

Adverum Clinical Site 172

Encino, California 91436

United States

Adverum Clinical Site 169

Fullerton, California 92835

United States

Adverum Clinical Site 224

Huntington Beach, California 92647

United States

Adverum Clinical Site 130

Poway, California 92064

United States

Adverum Clinical Site 215

Redlands, California 92374

United States

Adverum Clinical Site 140

Sacramento, California 95825

United States

Adverum Clinical Site 212

Sacramento, California 95841

United States

Adverum Clinical Site 175

Santa Barbara, California 93103

United States

Adverum Clinical Site 202

Torrance, California 90503

United States

Adverum Clinical Site 189

Walnut Creek, California 94598

United States

Adverum Clinical Site 200

Denver, Colorado 800222

United States

Adverum Clinical Site 116

Denver, Colorado 80207

United States

Adverum Clinical Site 165

Waterford, Connecticut 06385

United States

Adverum Clinical Site 124

Deerfield Beach, Florida 33064

United States

Adverum Clinical Site 184

Deerfield Beach, Florida 33064

United States

Adverum Clinical Site 176

Fort Lauderdale, Florida 33308

United States

Adverum Clinical Site 221

Fort Myers, Florida 33912

United States

Adverum Clinical Site 236

Gainesville, Florida 32607

United States

Adverum Clinical Site 214

Lakeland, Florida 33805

United States

Adverum Clinical Site 168

Miami Springs, Florida 33166

United States

Adverum Clinical Site 213

Orlando, Florida 32806

United States

Adverum Clinical Site 206

Plantation, Florida 33324

United States

Adverum Clinical Site 183

South Miami, Florida 33143

United States

Adverum Clinical Site 120

St. Petersburg, Florida 33711

United States

Adverum Clinical Site 148

Tampa, Florida 33609

United States

Adverum Clinical Site 238

Winter Haven, Florida 33880

United States

Adverum Clinical Site 182

Augusta, Georgia 30909

United States

Adverum Clinical Site 246

Chicago, Illinois 60616

United States

Adverum Clinical Site 179

Oak Forest, Illinois 60452

United States

Adverum Clinical Site 207

Oak Park, Illinois 60304

United States

Adverum Clinical Site 195

Carmel, Indiana 46032

United States

Adverum Clinical Site 205

Carmel, Indiana 46032

United States

Adverum Clinical Site 253

Carmel, Indiana 46032

United States

Adverum Clinical Site 197

Hagerstown, Maryland 21740

United States

Adverum Clinical Site 204

Hagerstown, Maryland 21740

United States

Adverum Clinical Site 216

Jackson, Mississippi 39202

United States

Adverum Clinical Site 240

Bloomfield, New Jersey 07003

United States

Adverum Clinical Site 171

Teaneck, New Jersey 07666

United States

Adverum Clinical Site 225

Liverpool, New York 13088

United States

Adverum Clinical Site 244

Rochester, New York 14620

United States

Adverum Clinical Site 196

Asheville, North Carolina 28803

United States

Adverum Clinical Site 234

Cary, North Carolina 27511

United States

Adverum Clinical Site 211

Greensboro, North Carolina 27401

United States

Adverum Clinical Site 219

Greensboro, North Carolina 27401

United States

Adverum Clinical Site 220

Hickory, North Carolina 28602

United States

Adverum Clinical Site 209

Wake Forest, North Carolina 27587

United States

Adverum Clinical Site 248

Beachwood, Ohio 44122-5846

United States

Adverum Clinical Site 247

Cleveland, Ohio 44130

United States

Adverum Clinical Site 254

Edmond, Oklahoma 73013

United States

Adverum Clinical Site 252

Portland, Oregon 97225

United States

Adverum Clinical Site 181

Erie, Pennsylvania 16505

United States

Adverum Clinical Site 239

Philadelphia, Pennsylvania 19102

United States

Adverum Clinical Site 110

Philadelphia, Pennsylvania 19107

United States

Adverum Clinical Site 241

Bluffton, South Carolina 29910

United States

Adverum Clinical Site 222

Ladson, South Carolina 29456

United States

Adverum Clinical Site 101

Nashville, Tennessee 37203

United States

Adverum Clinical Site 145

Arlington, Texas 76012

United States

Adverum Clinical Site 127

Austin, Texas 78705

United States

Adverum Clinical Site 243

Austin, Texas 78750

United States

Adverum Clinical Site 107

Conroe, Texas 77384

United States

Adverum Clinical Site 194

Dallas, Texas 75231

United States

Adverum Clinical Site 162

McAllen, Texas 78503

United States

Adverum Clinical Site 185

San Antonio, Texas 78240

United States

Adverum Clinical Site 232

San Marcos, Texas 78666

United States

Adverum Clinical Site 228

Schertz, Texas 78154

United States

Adverum Clinical Site 231

The Woodlands, Texas 77384

United States

Adverum Clinical Site 237

Tyler, Texas 75703

United States

Adverum Clinical Site 199

Lynchburg, Virginia 24502

United States

Adverum Clinical Site 249

Silverdale, Washington 98383

United States