Clinical trial NCT06856577: Efficacy and Safety Study of Ixoberogene Soroparvovec (Ixo-vec) in Participants With Neovascular Age-Related Macular Degeneration
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Neovascular Age-Related Macular Degeneration (nAMD)
Wet AMD
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
Adeno-associated viruses
Lead sponsor: Adverum Biotechnologies, Inc.
Sponsor class: INDUSTRY
First posted: 2025-03-04
Enrollment: 284
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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.

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.

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.

Eligibility 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 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.
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 criteria 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 Day 1.
   2. Uncontrolled hypertension defined as systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg.
   3. Stroke in the 6-month period prior to Day 1.
6. History of ongoing bleeding disorders
7. Use of systemic immunosuppressive drugs within 90 days prior to Screening Visit 1.
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 90 days prior to Screening Visit 1 (Day -56 to Day -49).
   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 Day 1.
4. Uncontrolled ocular hypertension or glaucoma in the study eye from Screening Visit 1 to Week 1.
5. Any history of intraocular pressure (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.

Primary outcomes:
measure: Mean Change from Baseline in Best-corrected Visual Acuity (BCVA) Post Study Drug Administration Based on an Average at Weeks 52 and 56
timeFrame: Baseline, Week 52 and Week 56
Secondary outcomes:
measure: Mean Number of Aflibercept IVT Injections Received
timeFrame: Through Week 56
measure: Percentage of Participants with worsened BCVA
timeFrame: Through Week 56
measure: Percentage of Participants with improved BCVA
timeFrame: Through Week 56
measure: Mean Change in BCVA from Baseline to Week 56
timeFrame: Through Week 56
measure: Percentage of Participants with BCVA of 73 Letters or More at Each Visit Starting at Week 4
timeFrame: Week 4 through Week 56
measure: Mean Change in Central Subfield Thickness (CST) from Baseline to Week 56
timeFrame: Through Week 56
measure: Mean Change in CST from Baseline to Each Post-baseline Visit
timeFrame: Through Week 56
measure: Percentage of Participants with CST ≤ 300 μm from Baseline to Each Post-baseline Visit Through Week 56
timeFrame: Through Week 56
measure: Mean Number of CST Fluctuations > 50 μm from Baseline Over Time Through Week 56
timeFrame: Baseline to Week 56
measure: Percentage of Participants with CST Fluctuations > 50 μm from Baseline Over Time Through Week 56
timeFrame: Through Week 56
measure: Percent Reduction in Annualized Anti-Vascular Endothelial Growth Factor (VEGF) Injections
timeFrame: Through Week 56
measure: Percentage of Participants who were Supplemental Aflibercept Injection-free
timeFrame: Through Week 56
measure: Percentage of Participants who Received 0 or 1 Supplemental Aflibercept Injection
timeFrame: Through Week 56
measure: Mean Change in Area of Choroidal Neovascularization (CNV) Lesion from Baseline to Week 56
timeFrame: Baseline to Week 56
measure: Mean Change in Macular Volume from Baseline to Week 56
timeFrame: Baseline to Week 56
measure: Percentage of Participants without Intraretinal Fluid (IRF)
timeFrame: Through Week 56
measure: Percentage of Participants without Subretinal Fluid (SRF)
timeFrame: Through Week 56
measure: Percentage of Participants Without IRF and/or SRF
timeFrame: Through Week 56
measure: Time to No IRF and SRF
timeFrame: Through Week 56
measure: Time to Sustain Dry Retina
timeFrame: Through Week 56
measure: Number of Participants who Experienced Ocular Adverse Events
timeFrame: Through Week 56
measure: Number of Participants who Experienced Mild, Moderate or Severe Ocular Adverse Events
timeFrame: Through Week 56
measure: Number of Participants who Experienced Non-ocular Adverse Events
timeFrame: Through Week 56
measure: Number of Participants who Experienced Mild, Moderate or Severe Non-ocular Adverse Events
timeFrame: Through Week 56
measure: Mean Change in 25-Item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) Total and Subscale Scores
timeFrame: Baseline, Week 28 and Week 56
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Adverum Clinical Site 223
state: Arizona
city: Phoenix
country: United States
facility: Adverum Clinical Site 178
state: Arizona
city: Phoenix
country: United States
facility: Adverum Clinical Site 126
state: Arizona
city: Tucson
country: United States
facility: Adverum Clinical Site 159
state: Arizona
city: Springdale
country: United States
facility: Adverum Clinical Site 198
state: Arkansas
city: Bakersfield
country: United States
facility: Adverum Clinical Site 109
state: California
city: Beverly Hills
country: United States
facility: Adverum Clinical Site 100
state: California
city: Campbell
country: United States
facility: Adverum Clinical Site 201
state: California
city: Encino
country: United States
facility: Adverum Clinical Site 172
state: California
city: Fullerton
country: United States
facility: Adverum Clinical Site 169
state: California
city: Sacramento
country: United States
facility: Adverum Clinical Site 140
state: California
city: Sacramento
country: United States
facility: Adverum Clinical Site 212
state: California
city: Santa Barbara
country: United States
facility: Adverum Clinical Site 175
state: California
city: Denver
country: United States
facility: Adverum Clinical Site 200
state: Colorado
city: Lakewood
country: United States
facility: Adverum Clinical Site 116
state: Colorado
city: Waterford
country: United States
facility: Adverum Clinical Site 165
state: Connecticut
city: Deerfield Beach
country: United States
facility: Adverum Clinical Site 184
state: Florida
city: Fort Lauderdale
country: United States
facility: Adverum Clinical Site 176
state: Florida
city: Fort Myers
country: United States
facility: Adverum Clinical Site 221
state: Florida
city: Jacksonville
country: United States
facility: Adverum Clinical Site 168
state: Florida
city: Orlando
country: United States
facility: Adverum Clinical Site 213
state: Florida
city: Pompano Beach
country: United States
facility: Adverum Clinical Site 124
state: Florida
city: South Miami
country: United States
facility: Adverum Clinical Site 183
state: Florida
city: Augusta
country: United States
facility: Adverum Clinical Site 182
state: Georgia
city: 'Aiea
country: United States
facility: Adverum Clinical Site 149
state: Hawaii
city: Oak Forest
country: United States
facility: Adverum Clinical Site 179
state: Illinois
city: Oak Park
country: United States
facility: Adverum Clinical Site 207
state: Illinois
city: Carmel
country: United States
facility: Adverum Clinical Site 205
state: Indiana
city: Hagerstown
country: United States
facility: Adverum Clinical Site 197
state: Maryland
city: Hagerstown
country: United States
facility: Adverum Clinical Site 204
state: Maryland
city: Detroit
country: United States
facility: Adverum Clinical Site 167
state: Michigan
city: Madison
country: United States
facility: Adverum Clinical Site 216
state: Mississippi
city: Saint Louis
country: United States
facility: Adverum Clinical Site 190
state: Missouri
city: Asheville
country: United States
facility: Adverum Clinical Site 196
state: North Carolina
city: Greensboro
country: United States
facility: Adverum Clinical Site 211
state: North Carolina
city: Wake Forest
country: United States
facility: Adverum Clinical Site 209
state: North Carolina
city: Winston-Salem
country: United States
facility: Adverum Clinical Site 219
state: North Carolina
city: Erie
country: United States
facility: Adverum Clinical Site 181
state: Pennsylvania
city: Philadelphia
country: United States
facility: Adverum Clinical Site 110
state: Pennsylvania
city: Ladson
country: United States
facility: Adverum Clinical Site 222
state: South Carolina
city: West Columbia
country: United States
facility: Adverum Clinical Site 122
state: South Carolina
city: Abilene
country: United States
facility: Adverum Clinical Site 123
state: Texas
city: Austin
country: United States
facility: Adverum Clinical Site 127
state: Texas
city: Bellaire
country: United States
facility: Adverum Clinical Site 108
state: Texas
city: Burleson
country: United States
facility: Adverum Clinical Site 227
state: Texas
city: Dallas
country: United States
facility: Adverum Clinical Site 194
state: Texas
city: Houston
country: United States
facility: Adverum Clinical Site 188
state: Texas
city: McAllen
country: United States
facility: Adverum Clinical Site 162
state: Texas
city: San Antonio
country: United States
facility: Adverum Clinical Site 185
state: Texas
city: The Woodlands
country: United States
facility: Adverum Clinical Site 107
state: Texas
city: Lynchburg
country: United States
facility: Adverum Clinical Site 199
state: Virginia
city: Wausau
country: United States
facility: Adverum Clinical Site 187
state: Wisconsin
Study officials:
affiliation: Adverum Biotechnologies, Inc.
name: Adam Turpcu, PhD
role: STUDY_DIRECTOR
References: