ADVM-022 Intravitreal Gene Therapy for DME (INFINITY)

Adverum Biotechnologies

Status and phase: Completed; Phase 2

Conditions: Diabetic Macular Edema; Diabetic Retinopathy

Treatments: Biological: Aflibercept; Biological: 6E11 vg/eye of ADVM-022; Biological: 2E11 vg/eye of ADVM-022

Study type: Interventional

Funder types: Industry

Identifiers

NCT04418427

ADVM-022-04

Details and patient eligibility

About

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

Full description

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.

Enrollment: 36 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 3 patient groups

1

Experimental group

Description:

6E11 vg/eye ADVM-022 +/- aflibercept 2mg IVT

Treatment:

Biological: 6E11 vg/eye of ADVM-022

Biological: Aflibercept

2

Experimental group

Description:

2E11 vg/eye ADVM022 +/- aflibercept 2mg IVT

Treatment:

Biological: 2E11 vg/eye of ADVM-022

Biological: Aflibercept

3

Active Comparator group

Description:

Aflibercept 2mg IVT

Treatment:

Biological: Aflibercept