Neovascular Age-Related Macular Degeneration (nAMD)Phase 3ARTEMISNCT06856577
Efficacy and Safety Study of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-Related Macular Degeneration
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 75 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
- 311 participants
- Where
- 75 sitesUnited States
- Study dates
- 28 Feb 2025to 23 Nov 2030
- 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 Early Treatment Diabetic Retinopathy Study (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 criteria 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:
Show all 29Show fewer
- 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 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 intraocular pressure (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
75 sites in 1 country.
75 sites in 1 country
United States75 sites
Adverum Clinical Site 123
Abilene, Texas, 79606
Adverum Clinical Site 196
Asheville, North Carolina, 28803
Adverum Clinical Site 182
Augusta, Georgia, 30909
Adverum Clinical Site 127
Austin, Texas, 78705
Adverum Clinical Site 109
Bakersfield, California, 93309
Adverum Clinical Site 108
Bellaire, Texas, 77401
Adverum Clinical Site 100
Beverly Hills, California, 90211
Adverum Clinical Site 227
Burleson, Texas, 76028
Adverum Clinical Site 201
Campbell, California, 95008
Adverum Clinical Site 195
Carmel, Indiana, 46032
Adverum Clinical Site 205
Carmel, Indiana, 46032
Adverum Clinical Site 234
Cary, North Carolina, 27511
Adverum Clinical Site 208
Charleston, South Carolina, 29414
Adverum Clinical Site 194
Dallas, Texas, 75231
Adverum Clinical Site 184
Deerfield Beach, Florida, 33064
Adverum Clinical Site 200
Denver, Colorado, 80222
Adverum Clinical Site 167
Detroit, Michigan, 48201
Adverum Clinical Site 186
Durham, North Carolina, 27705
Adverum Clinical Site 172
Encino, California, 91436
Adverum Clinical Site 181
Erie, Pennsylvania, 16507
Adverum Clinical Site 176
Fort Lauderdale, Florida, 33308
Adverum Clinical Site 221
Fort Myers, Florida, 33912
Adverum Clinical Site 169
Fullerton, California, 92835
Adverum Clinical Site 223
Gilbert, Arizona, 85297
Adverum Clinical Site 211
Greensboro, North Carolina, 27401
Adverum Clinical Site 197
Hagerstown, Maryland, 21740
Adverum Clinical Site 204
Hagerstown, Maryland, 21740
Adverum Clinical Site 220
Hickory, North Carolina, 28602
Adverum Clinical Site 188
Houston, Texas, 77030
Adverum Clinical Site 224
Huntington Beach, California, 92647
Adverum Clinical Site 168
Jacksonville, Florida, 32216
Adverum Clinical Site 218
Katy, Texas, 77494
Adverum Clinical Site 222
Ladson, South Carolina, 29456
Adverum Clinical Site 214
Lakeland, Florida, 33805
Adverum Clinical Site 116
Lakewood, Colorado, 80228
Adverum Clinical Site 225
Liverpool, New York, 13088
Adverum Clinical Site 199
Lynchburg, Virginia, 24502
Adverum Clinical Site 216
Madison, Mississippi, 39110
Adverum Clinical Site 162
McAllen, Texas, 78503
Adverum Clinical Site 179
Oak Forest, Illinois, 60452
Adverum Clinical Site 207
Oak Park, Illinois, 60304
Adverum Clinical Site 213
Orlando, Florida, 32806
Adverum Clinical Site 230
Pensacola, Florida, 32503
Adverum Clinical Site 110
Philadelphia, Pennsylvania, 19107
Adverum Clinical Site 178
Phoenix, Arizona, 85021
Adverum Clinical Site 126
Phoenix, Arizona, 85053
Adverum Clinical Site 124
Pompano Beach, Florida, 33064
Adverum Clinical Site 144
Rapid City, South Dakota, 57701
Adverum Clinical Site 215
Redlands, California, 92374
Adverum Clinical Site 164
Riverside, California, 92505
Adverum Clinical Site 140
Sacramento, California, 95825
Adverum Clinical Site 212
Sacramento, California, 95841
Adverum Clinical Site 185
San Antonio, Texas, 78240
Adverum Clinical Site 232
San Marcos, Texas, 78666
Adverum Clinical Site 175
Santa Barbara, California, 93103
Adverum Clinical Site 228
Schertz, Texas, 78154
Adverum Clinical Site 229
Scottsdale, Arizona, 85255
Adverum Clinical Site 183
South Miami, Florida, 33143
Adverum Clinical Site 163
Southaven, Mississippi, 38671
Adverum Clinical Site 131
Spokane, Washington, 99204
Adverum Clinical Site 198
Springdale, Arkansas, 72764
Adverum Clinical Site 190
St Louis, Missouri, 63128
Adverum Clinical Site 120
St. Petersburg, Florida, 33711
Adverum Clinical Site 193
Tampa, Florida, 33617
Adverum Clinical Site 171
Teaneck, New Jersey, 07666
Adverum Clinical Site 107
The Woodlands, Texas, 77384
Adverum Clinical Site 231
The Woodlands, Texas, 77384
Adverum Clinical Site 202
Torrance, California, 90503
Adverum Clinical Site 159
Tucson, Arizona, 85704
Adverum Clinical Site 209
Wake Forest, North Carolina, 27587
Adverum Clinical Site 189
Walnut Creek, California, 94598
Adverum Clinical Site 165
Waterford, Connecticut, 06385
Adverum Clinical Site 187
Wausau, Wisconsin, 54403
Adverum Clinical Site 122
West Columbia, South Carolina, 29169
Adverum Clinical Site 219
Winston-Salem, North Carolina, 27103
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 (ARTEMIS)
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.
Read the detailed description
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).
- Being tested
- Ixo-vec, Aflibercept
- Keywords
- Ixoberogene soroparvovec, Ixo-vec, Aflibercept, Neovascular age-related macular degeneration, nAMD, ADVM, ADVM-022, ADVM-022-12, Wet AMD, wAMD, Wet Age-related Macular Degeneration, CNV, Neovascular AMD, AAV, AAV vector, AAV.7m8-aflibercept, AAV.7m8, Gene therapy, Eye disease, Blindness
- 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 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.
Measured: Baseline, Week 52 and Week 56
Secondary outcomes (27)
Mean number of aflibercept IVT injections received
Measured: Week 4 through Week 56
Percentage of participants with worsened BCVA from Baseline through Week 56 and Week 104
BCVA measured by ETDRS
Measured: 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
Measured: Baseline through Week 56 and Week 104
Mean change from Baseline in BCVA through Week 104
BCVA measured by ETDRS
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: Week 1 through Week 56 and Week 104
Mean number of aflibercept IVT injections received from Week 4 through Week 104
Measured: 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
Measured: Week 56 and Week 104
Percentage of participants who were aflibercept injection-free
Measured: Week 4 through Week 56 and through Week 104
Percentage of participants who received 0 or 1 aflibercept injection
Measured: 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
Measured: 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.
Measured: 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.
Measured: Baseline through Week 104
Percentage of participants without Intraretinal Fluid (IRF) through Week 104
IRF will be assessed using SD-OCT
Measured: Through Week 104
Percentage of participants without Subretinal Fluid (SRF) through Week 104
SRF will be assessed using SD-OCT
Measured: 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
Measured: 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
Measured: 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.
Measured: Through Week 104
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 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 to Week 28, Week 56, and Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2025
- Study start28 Feb 2025
- Primary completion22 Dec 2026 (estimated)
- Study completion23 Nov 2030 (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
- 311 participants (actual)
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
- NCT06856577
- Sponsor's protocol ID
- ADVM-022-12
- Acronym
- ARTEMIS
- Status last verified
- May 2026
- First submitted
- 26 Feb 2025
- Last updated
- 22 May 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 the identity of participants and to protect sensitive and confidential information. For inquiries, please contact us at datasharing@adverum.com.