ADVM-022 Intravitreal Gene Therapy for DME

Phase 2

Completed

• Conditions: Diabetic Macular Edema; Diabetic Retinopathy
• Interventions: Biological: Aflibercept; Biological: 6E11 vg/eye of ADVM-022; Biological: 2E11 vg/eye of ADVM-022

• Registration Number: NCT04418427
• Lead Sponsor: Adverum Biotechnologies, Inc.

Brief Summary

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

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.

Study Timeline

• Study Start: 2020-05-28
• Study First Submitted: 2020-05-28
• Study First Submitted QC: 2020-06-03
• Study First Posted: 2020-06-05
• Primary Completion: 2022-11-22
• Study Completion: 2022-11-22
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-06
• Last Update Posted: 2023-08-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
3	Aflibercept	Aflibercept 2mg IVT
2	Aflibercept	2E11 vg/eye ADVM022 +/- aflibercept 2mg IVT
1	6E11 vg/eye of ADVM-022	6E11 vg/eye ADVM-022 +/- aflibercept 2mg IVT
1	Aflibercept	6E11 vg/eye ADVM-022 +/- aflibercept 2mg IVT
2	2E11 vg/eye of ADVM-022	2E11 vg/eye ADVM022 +/- aflibercept 2mg IVT

Primary Outcome Measures

Name	Time	Method
Time to worsening of DME disease activity in the study eye.	96 weeks	Time to worsening of DME disease activity in the study eye.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Adverum Clinical Site; 🇵🇷 Arecibo, Puerto Rico