Neovascular Age-related Macular Degeneration
Conditions
Keywords
Aflibercept, Best Corrected Visual Acuity, Adverum, ADVM, ADVM-022, ADVM-022-11, Age-related macular degeneration, Wet macular degeneration, Wet AMD, Choroidal neovascularization, CNV, AAV.7m8, Anti-VEGF therapy, Gene therapy, Blindness, AAV, AAV vector, nAMD, wAMD, Eye disease, Eye diseases
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.
Interventions
GENETICADVM-022
A single IVT injection of 2E11 vg/eye ADVM-022 dose in combination with one (1) of four (4) corticosteroid treatment regimens
Sponsors
Adverum Biotechnologies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of ocular and non-ocular adverse events | Up to Week 52 | Incidence of ocular and non-ocular adverse events |
| Severity of ocular and non-ocular adverse events | Up to Week 52 | Severity 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants who are supplemental aflibercept injection-free | Baseline up to 5 years | Supplemental anti-VEGF treatments required post therapy |
| Percent reduction in annualized anti-VEGF injections | Baseline up to 5 years | Supplemental annualized anti-VEGF treatments required post therapy to the year prior |
| Mean change in Central Subfield Thickness (CST) from Baseline | Baseline up to 5 years | To evaluate the effect of ADVM-022 on CST |
| Mean number of CST fluctuations from Baseline | 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 |
| 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 |
| 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 without CST fluctuations | Baseline up to 5 years | To evaluate the effect of ADVM-022 on CST |
| 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 |
Countries
France, United Kingdom, United States
Outcome results
None listed