ADVM-022 Intravitreal Gene Therapy for DME

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-28

Study Completion Date

2023-06-14

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 \[INFINITY\]

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Detailed Description

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ADVM-022 (also known as Ixo-vec and AAV.7m8-aflibercept) is an investigational gene therapy product developed for the treatment of serious retinal vascular diseases including Diabetic Macular Edema (DME), a vision-threatening complication of diabetic retinopathy. DME can affect up to 10% of individuals with both type 1 and type 2 diabetes mellitus. Current therapies for treating DME include anti-vascular endothelial growth factor (anti-VEGF) agents that require frequent and long-term intravitreal (IVT) injections to achieve and maintain efficacy. ADVM-022 is intended provide sustained intraocular expression of aflibercept from a single IVT injection to potentially reduce the current treatment burden and prevent disease progression and vision loss due to undertreatment.

This Phase 2, randomized, controlled study (INFINITY) enrolled 36 eligible participants with DME. The participants were randomized to receive one of the two dose levels of ADVM-022 or assigned to the control arm to receive a sham ocular injection with a preceding aflibercept injection. Participants randomized to the ADVM-022 arms were assigned to receive a preceding aflibercept or sham ocular injection. All participants were monitored regularly for disease activity and may have received supplemental aflibercept based on predefined retreatment criteria. All participants were to be followed over a 96- week follow-up period.

To enhance safety monitoring for participants in this study, the sponsor unmasked treatment assignment (in April 2021) due to the occurrence of a suspected unexpected serious adverse reaction (SUSAR) which occurred early in the study in the high dose (ADVM-022 6E11 vg/eye) arm. Interpretation of the results of this study should consider the potential confounding nature of this unmasking in the context of the observed dose-limiting events and the associated additional use of topical/intravitreal/systemic steroids, particularly in the high dose ADVM-022 arm.

In this study ADVM-022 (Ixo-vec) demonstrated improved efficacy across endpoints, reducing the need for supplemental aflibercept in DME management and demonstrating a clinically meaningful delay in DME worsening and improved outcomes across multiple endpoints compared to the control arm (sham + Aflibercept). However, the benefit of the ADVM-022 6E11 vg/eye dose was affected by dose-limiting toxicities in some participants. In terms of safety outcomes, the most common ADVM-022-related adverse events were mild-to-moderate intraocular inflammation, a known and expected side effect of ocular gene therapy, which was generally responsive to corticosteroid eye drops. No Ixo-vec-related events were reported in the fellow eye or systemically, indicating no off-target effects.

Conditions

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Diabetic Macular Edema Diabetic Retinopathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

From May 2020 through April 2021: Double-masked study - participants, outcomes assessors and the designated masked study personnel were to have been masked to subject's treatment assignment throughout the study. There must have been a minimum of two physicians per site to fulfill the masking requirements of the study. A masked and unmasked investigator were 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 was required to be present.

Starting April 2021: Open label study - study was unmasked for enhanced safety monitoring.

Intervention Type BIOLOGICAL

Commercially available Active Comparator

Interventions

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6E11 vg/eye of ADVM-022

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

Intervention Type BIOLOGICAL

2E11 vg/eye of ADVM-022

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

Intervention Type BIOLOGICAL

Aflibercept

Commercially available Active Comparator

Intervention Type BIOLOGICAL

Other Intervention Names

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AAV.7m8-aflibercept AAV.7m8-aflibercept Eylea

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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No