ADVM-022 Intravitreal Gene Therapy for DME (INFINITY)

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

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

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.

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

From May 2020 through April 2021: Double-masked study Subjects, outcomes assessors and the designated masked study personnel will be masked to subject's treatment assignment throughout the study. There must be a minimum of two physicians per site to fulfill the masking requirements of the study. A masked and unmasked investigator are required to be present for administration of the preceding dose of aflibercept or sham and following dose of ADVM-022 or sham visits, thereafter only the masked investigator is required to be present. Starting May 2021: Open label study, study was unmasked for enhance safety monitoring.

ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept

ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept

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

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

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