Safety and Efficacy of ADVM-022 in Treatment-Experienced Patients With Neovascular Age-related Macular Degeneration
Study Details
Study Description
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 4-12 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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 dose levels (2 × 1011 vg/eye [2E11] or 6 × 1010 vg/eye [6E10]) accompanied by one of four prophylactic corticosteroid treatment regimens. Approximately, 72 anti-VEGF treatment-experienced study participants meeting the eligibility criteria will be randomized equally between the 2E11 vg/eye and 6E10 vg/eye ADVM-022 doses across four prophylactic corticosteroid regimens, 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 1 year from baseline.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose 1 A single intravitreal injection of ADVM-022 2E11 vg/eye |
Genetic: ADVM-022
A single IVT injection of 2E11 vg/eye ADVM-022 dose in combination with one (1) of four (4) corticosteroid treatment regimens
|
| Experimental: Dose 2 A single intravitreal injection of ADVM-022 6E10 vg/eye |
Genetic: ADVM-022
A single IVT injection of 6E10 vg/eye ADVM-022 dose in combination with one (1) of four (4) corticosteroid treatment regimens
|
Outcome Measures
Primary Outcome Measures
- Severity of ocular and non-ocular adverse events [From Baseline to Week 50]
Incidence of ocular and non-ocular adverse events
- Incidence of ocular and non-ocular adverse events [From Baseline to Week 50]
Incidence of ocular and non-ocular adverse events
- Mean change in best corrected visual acuity (BCVA) from Baseline [Week 50]
BCVA measured by Early Treatment Diabetic Retinopathy Study (ETDRS)
Secondary Outcome Measures
- Percentage of participants from Baseline who lose/gain at least 5, 10 or 15 letters in Best Corrected Visual Acuity (BCVA) [Week 50]
BCVA measured by ETDRS
- Mean change in BCVA from Baseline [Week 26]
BCVA measured by ETDRS
- Percentage of participants who are supplemental aflibercept injection-free [Week 50]
Supplemental anti-VEGF treatments required post therapy
- Percentage reduction in anti-VEGF injections [Week 50]
Supplemental anti-VEGF treatments required post therapy to the year prior
- Mean change in Central Subfield Thickness (CST) from Baseline [Week 26 and Week 50]
To evaluate the effect of ADVM-022 on CST
- Percentage of participants without CST fluctuations > 50 μm [Week 50]
To evaluate the effect of ADVM-022 on CST
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female participants, age ≥ 50 years of age
-
Willing and able to provide written, signed informed consent for this study
-
Demonstrated a meaningful response to anti-VEGF therapy.
-
Current evidence of active primary or recurrent sub-foveal choroidal neovascularization (CNV) assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
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Subjects must be under active anti-VEGF treatment for wet AMD and received a minimum of 2 injections within 4 months prior to screening
-
BCVA ETDRS Snellen equivalent between ≤20/32 and ≥20/320
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
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Ocular or periocular infection or intraocular inflammation in either eye within 1 month prior to or at the Randomization Visit (Day -7)
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Uncontrolled diabetes or HbA1c ≥ 7.0 %
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History or evidence of significant uncontrolled concomitant disease within 6 months of the Screening visit
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History within the 12 months prior to Screening or evidence of renal or hepatic dysfunction at Screening
-
Any history of ongoing bleeding disorders or INR >3.0
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History or evidence of macular or retinal disease other than nAMD
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Active or history of retinal detachment or retinal pigment epithelium rip/tear
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Uncontrolled ocular hypertension or glaucoma
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Prior treatment with photodynamic therapy or retinal laser for the treatment of nAMD
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Any history of vitrectomy or any other vitreoretinal surgery within 3 months prior to the Randomization Visit (Day -7)
-
Prior treatment with gene therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Adverum Clinical Site | Phoenix | Arizona | United States | 85053 |
| 2 | Adverum Clinical Site | Fullerton | California | United States | 92835 |
| 3 | Adverum Clinical Site | Jacksonville | Florida | United States | 32216 |
| 4 | Adverum Clinical Site | 'Aiea | Hawaii | United States | 96701 |
| 5 | Adverum Clinical Site | San Antonio | Texas | United States | 78240 |
Sponsors and Collaborators
- Adverum Biotechnologies, Inc.
- Parexel
Investigators
- Study Director: Adam Turpcu, PhD, Adverum Biotechnologies, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ADVM-022-11