Safety and Efficacy of ADVM-022 in Treatment-Experienced Patients With Neovascular Age-related Macular Degeneration [LUNA]
- Conditions
- Neovascular Age-related Macular Degeneration
- Interventions
- Genetic: ADVM-022
- Registration Number
- NCT05536973
- Lead Sponsor
- Adverum Biotechnologies, Inc.
- Brief Summary
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. ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product being developed for the treatment of nAMD and offers the potential for sustained intraocular expression of aflibercept following a single IVT injection. ADVM-022 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.
- Detailed Description
This Phase 2, multi-center, randomized, double-masked, parallel group study is designed to evaluate the safety, tolerability, and efficacy of a single IVT injection of ADVM-022 at one of two doses (2 × 10\^11 vg/eye \[2E11\] or 6 × 10\^10 vg/eye \[6E10\]) accompanied by one of four prophylactic corticosteroid treatment regimens.
Anti-VEGF treatment-experienced study participants meeting the eligibility criteria that will be randomized between the 2E11 vg/eye and 6E10 vg/eye ADVM-022 doses each with 4 prophylaxis arms for a total of 8 treatment arms, and only one eye per study participant will be selected as the study eye.
Safety, tolerability, and efficacy will be evaluated for a period of approximately 5 years from baseline.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 69
- Male or female participants, ≥ 50 years of age
- Willing and able to provide written, signed informed consent for this study
- Demonstrated a meaningful response to anti-VEGF therapy
- Participants must be under active anti-VEGF treatment for wet AMD and received a minimum of 2 injections within 4 months prior to screening for the treatment of choroidal neovascularization secondary to nAMD in the study eye
- Vision of the study eye at Baseline: BCVA in the range of 25 - 83 ETDRS letters, inclusive (approximate Snellen equivalent visual acuity range of 20/25 - 20/320)
- Vision of the non-study eye at Baseline: BCVA ≥ 35 ETDRS letters (approximate Snellen equivalent of 20/200 or better)
- Any condition that could affect the interpretation of results or render the participant at high risk of treatment complications in the opinion of the Investigator
- Ocular or periocular infection or intraocular inflammation in either eye within 1 month prior to or at the Randomization Visit (Day -7)
- Uncontrolled diabetes or HbA1c ≥ 7.0 %
- History or evidence of significant uncontrolled concomitant disease within 6 months of the Screening visit
- Any history of ongoing bleeding disorders or INR >3.0
- History or evidence of macular or retinal disease other than nAMD
- History or evidence of retinal detachment or retinal pigment epithelium rip/tear
- Uncontrolled ocular hypertension or glaucoma
- Prior treatment with photodynamic therapy or retinal laser for the treatment of nAMD
- Any history of vitrectomy or any other vitreoretinal surgery
- Prior treatment with gene therapy at any time or any non-gene therapy investigational treatment or medical device in the study eye within 3 months of the Screening Visit or 5 half-lives of the investigational medicinal product
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose 2 ADVM-022 A single intravitreal injection of ADVM-022 6E10 vg/eye Dose 1 ADVM-022 A single intravitreal injection of ADVM-022 2E11 vg/eye
- Primary Outcome Measures
Name Time Method Severity of ocular and non-ocular adverse events Up to Week 52 Severity of ocular and non-ocular adverse events
Incidence of ocular and non-ocular adverse events Up to Week 52 Incidence of ocular and non-ocular adverse events
Mean change in best corrected visual acuity (BCVA) from Baseline Baseline up to Week 52 BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)
- Secondary Outcome Measures
Name Time Method Mean number of CST fluctuations from Baseline Baseline up to 5 years To evaluate the effect of ADVM-022 on CST
Incidence of ocular and non-ocular adverse events Up to 60 months To assess the long-term safety and tolerability of a single IVT injection of ADVM-022
Percentage of participants without CST fluctuations Baseline up to 5 years To evaluate the effect of ADVM-022 on CST
Percentage of participants without post-prophylactic inflammation Baseline up to 5 years To assess the long-term safety and tolerability of a single IVT injection of ADVM-022
Percentage of participants from Baseline who lose/gain at least 5, 10 or 15 letters in BCVA Baseline up to 5 years BCVA measured by ETDRS
Mean change in BCVA from Baseline Baseline up to 5 years BCVA measured by ETDRS
Severity of ocular and non-ocular adverse events Up to 60 months To assess the long-term safety and tolerability of a single IVT injection of ADVM-022
Percentage of participants who are supplemental aflibercept injection-free Baseline up to 5 years Supplemental anti-VEGF treatments required post therapy
Mean change in Central Subfield Thickness (CST) from Baseline Baseline up to 5 years To evaluate the effect of ADVM-022 on CST
Percent reduction in annualized anti-VEGF injections Baseline up to 5 years Supplemental annualized anti-VEGF treatments required post therapy to the year prior
Trial Locations
- Locations (39)
Adverum Clinical Site 162
🇺🇸McAllen, Texas, United States
Adverum Clinical Site 108
🇺🇸Bellaire, Texas, United States
Adverum Clinical Site 601
🇬🇧Oxford, United Kingdom
Adverum Clinical Site 600
🇬🇧London, United Kingdom
Adverum Clinical Site 107
🇺🇸The Woodlands, Texas, United States
Adverum Clinical Site 161
🇺🇸Royal Oak, Michigan, United States
Adverum Clinical Site 152
🇺🇸Morgantown, West Virginia, United States
Adverum Clinical Site 100
🇺🇸Beverly Hills, California, United States
Adverum Clinical Site 172
🇺🇸Encino, California, United States
Adverum Clinical Site 169
🇺🇸Fullerton, California, United States
Adverum Clinical Site 170
🇺🇸Pasadena, California, United States
Adverum Clinical Site 174
🇺🇸Poway, California, United States
Adverum Clinical Site 164
🇺🇸Riverside, California, United States
Adverum Clinical Site 175
🇺🇸Santa Barbara, California, United States
Adverum Clinical Site 116
🇺🇸Lakewood, Colorado, United States
Adverum Clinical Site 176
🇺🇸Fort Lauderdale, Florida, United States
Adverum Clinical Site 124
🇺🇸Deerfield Beach, Florida, United States
Adverum Clinical Site 168
🇺🇸Jacksonville, Florida, United States
Adverum Clinical Site 171
🇺🇸Teaneck, New Jersey, United States
Adverum Clinical Site 144
🇺🇸Rapid City, South Dakota, United States
Adverum Clinical Site 123
🇺🇸Abilene, Texas, United States
Adverum Clinical Site 149
🇺🇸'Aiea, Hawaii, United States
Adverum Clinical Site 167
🇺🇸Detroit, Michigan, United States
Adverum Clinical Site 101
🇺🇸Nashville, Tennessee, United States
Adverum Clinical Site 151
🇺🇸San Antonio, Texas, United States
Adverum Clinical Site 126
🇺🇸Phoenix, Arizona, United States
Adverum Clinical Site 159
🇺🇸Tucson, Arizona, United States
Adverum Clinical Site 178
🇺🇸Phoenix, Arizona, United States
Adverum Clinical Site 122
🇺🇸West Columbia, South Carolina, United States
Adverum Clinical Site 501
🇫🇷Lyon, Rhône, France
Adverum Clinical Site 119
🇺🇸Reno, Nevada, United States
Adverum Clinical Site 165
🇺🇸Waterford, Connecticut, United States
Adverum Clinical Site 146
🇺🇸Cherry Hill, New Jersey, United States
Adverum Clinical Site 502
🇫🇷Nantes, Loire-Atlantique, France
Adverum Clinical Site 163
🇺🇸Southaven, Mississippi, United States
Adverum Clinical Site 500
🇫🇷Créteil, Val-de-Marne, France
Adverum Clinical Site 177
🇺🇸Omaha, Nebraska, United States
Adverum Clinical Site 166
🇺🇸Sacramento, California, United States
Adverum Clinical Site 154
🇺🇸Austin, Texas, United States