ADVM-022 Intravitreal Gene Therapy for DME

Study Overview
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Brief Summary
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A Phase 2, Multi-Center, Randomized, Double-Masked*, Active Controlled Study of ADVM-022 (AAV.7m8-aflibercept) in Subjects with Diabetic Macular Edema [INFINITY] *sponsor unmasked for enhanced safety monitoring as of May 2021

Detailed Description
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ADVM-022 (AAV.7m8-aflibercept) is a gene therapy product developed for the treatment of serious retinal vascular diseases including Diabetic Macular Edema (DME). DME affects up to 10% of people with diabetes is caused by fluid accumulation in the macula and is the most frequent cause of sight loss in people with diabetic retinopathy. Available therapies for treating DME include laser and anti-vascular endothelial growth factor (anti-VEGF) drugs. Anti-VEGFs require frequent and long-term intravitreal (IVT) injections to achieve and maintain efficacy. A one-time IVT administration of ADVM-022 has the potential to treat DME by providing durable expression of an anti-VEGF protein (aflibercept) to limit abnormal blood vessel leakage. ADVM-022 is designed to reduce the current treatment burden which often results in undertreatment, progression of disease and subsequent vision loss in patients with DME. In INFINITY, approximately 33 eligible subjects will be randomly assigned to receive one of the two doses of ADVM-022, or, assigned to the control arm to receive a sham ocular injection with a preceding aflibercept injection. Subjects who are assigned to receive ADVM-022 will be further randomized to receive a preceding aflibercept or sham ocular injection. All subjects will be assessed regularly and will receive additional aflibercept injections should DME disease activity progress. The primary objective is to assess the durability of a single intravitreal (IVT) injection of ADVM-022. All subjects will be followed for 96 weeks after randomization.

Official Title
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A Phase 2, Multi-Center, Randomized, Double-Masked, Active Controlled Study of ADVM-022 (AAV.7m8-aflibercept) in Subjects With Diabetic Macular Edema [INFINITY]

Conditions
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Diabetic Macular Edema, Diabetic Retinopathy

Intervention / Treatment
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* Biological: 6E11 vg/eye of ADVM-022
* Biological: 2E11 vg/eye of ADVM-022
* Biological: Aflibercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 Type 1 or Type 2 diabetes mellitus Willing and able to provide informed consent Vision impairment due to center involving diabetic macular edema Exclusion Criteria: Uncontrolled diabetes defined as HbA1C >10%, or history of diabetic ketoacidosis within 3 months prior to randomization; or subjects who, within the last 3 months, initiated intensive insulin treatment (a pump or multiple daily injection) or plan to do so in the next 3 months. Acute coronary syndrome, myocardial infarction or coronary artery revascularization, CVA, TIA in the last 6 months Uncontrolled hypertension defined as average SBP ≥160 mmHg or an average DBP ≥100 mmHg Known severe renal impairment High risk Proliferative Diabetic Retinopathy History of retinal disease in the study eye other than diabetic retinopathy History of retinal detachment (with or without repair) in the study eye History of vitrectomy, trabeculectomy, or other filtration surgery in the study eye Any prior focal or grid laser photocoagulation or any prior PRP in the study eye Current or planned pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>6E11 vg/eye ADVM-022 +/- aflibercept 2mg IVT | Biological: 6E11 vg/eye of ADVM-022<br>* ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept<br>* Other names: AAV.7m8-aflibercept;Biological: Aflibercept<br>* Commercially available Active Comparator<br>* Other names: Eylea;|
| Experimental: 2<br>2E11 vg/eye ADVM022 +/- aflibercept 2mg IVT | Biological: 2E11 vg/eye of ADVM-022<br>* ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept<br>* Other names: AAV.7m8-aflibercept;Biological: Aflibercept<br>* Commercially available Active Comparator<br>* Other names: Eylea;|
| Active Comparator: 3<br>Aflibercept 2mg IVT | Biological: Aflibercept<br>* Commercially available Active Comparator<br>* Other names: Eylea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to worsening of DME disease activity in the study eye. | Time to worsening of DME disease activity in the study eye. | 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of ocular and non-ocular adverse events (AEs) | Incidence and severity of ocular and non-ocular adverse events (AEs) | 96 weeks | 
| Change from Baseline in central subfield thickness (CST) and macular volume over time measured by SD-OCT | Change from Baseline in central subfield thickness (CST) and macular volume over time measured by SD-OCT | 96 weeks | 
| Change from Baseline in BCVA over time | Change from Baseline in BCVA over time | 96 weeks | 
| Frequency of rescue aflibercept (2 mg IVT) in the study eye over time during the study | Frequency of rescue aflibercept (2 mg IVT) in the study eye over time during the study | 96 weeks | 
| Incidence of improvement in DRSS score over time | Incidence of improvement in DRSS score over time | 96 weeks | 
| Incidence of worsening in DRSS score over time | Incidence of worsening in DRSS score over time | 96 weeks | 
| Occurrence of vision threatening complication over time | Occurrence of vision threatening complication over time | 96 weeks | 
| Incidence of CST <300 μm over time through Week 48 | Incidence of CST <300 μm over time through Week 48 | 96 weeks | 
| Incidence of clinically significant findings via physical examinations, ocular examinations, imaging, and laboratory evaluation | Incidence of clinically significant findings via physical examinations, ocular examinations, imaging, and laboratory evaluation | 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADVM-022, ADVM-022-04, AAV.7m8, Anti-VEGF therapy, Blindness, INFINITY, Gene therapy, Aflibercept (Eylea), Retinal Diseases, Eye Diseases, AAV Vector, Adverum, DME, Diabetic macular edema, Diabetic eye disease, Diabetic retinopathy, DR, AAV.7m8-aflibercept