ADVM-022 Intravitreal Gene Therapy for DME

NCT04418427 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ADVM-022-04
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 14

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 \[INFINITY\]

Conditions

Diabetic Macular Edema; Diabetic Retinopathy

Keywords

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; Ixoberogene soroparvovec; Ixo-vec

Outcome Measures

Primary Outcomes (1)

• Time to Worsening of DME Disease Activity in the Study Eye.

  Time to worsening of DME disease activity in the study eye through 96 weeks. Time to worsening of DME disease activity defined by either: An increase in CST \> 50 µm as assessed by SD-OCT compared to the lower of the two CST measurements recorded at Day 1 or Week 4; A loss of \> 5 letters in BCVA due to worsening DME disease activity compared to the higher of the two BCVA measurements recorded at Day 1 or Week 4. Number of weeks was relative to Day 1.

  Day 1 through 96 weeks

Secondary Outcomes (11)

• Incidence of Ocular Adverse Events (AEs)

  96 weeks

• Incidence of Non-ocular Adverse Events (AEs)

  Day 1 through 96 weeks

• Change From Baseline Central Subfield Thickness (CST) in Study Eye

  Baseline through 96 weeks

• Change From Baseline in Best Corrected Visual Acuity (BCVA) Score Over Time in the Study Eye

  96 weeks

• Frequency of Supplemental Aflibercept Injections (2 mg IVT) in the Study Eye Over Time During the Study

  Day 1 through 96 weeks

Study Arms (3)

1

EXPERIMENTAL

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

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

2

EXPERIMENTAL

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

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

3

ACTIVE COMPARATOR

Aflibercept 2mg IVT

Biological: Aflibercept

Interventions

6E11 vg/eye of ADVM-022 BIOLOGICAL

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

Also known as: AAV.7m8-aflibercept

1

2E11 vg/eye of ADVM-022 BIOLOGICAL

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

Also known as: AAV.7m8-aflibercept

2

Aflibercept BIOLOGICAL

Commercially available Active Comparator

Also known as: Eylea

1; 2; 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Adverum Biotechnologies, Inc.: lead

Study Sites (14)

Adverum Clinical Site

Phoenix, Arizona, 85014, United States

Location

Adverum Clinical Site

Bakersfield, California, 93309, United States

Location

Adverum Clinical Site

Beverly Hills, California, 90211, United States

Location

Adverum Clinical Site

Golden, Colorado, 80401, United States

Location

Adverum Clinical Site

Deerfield Beach, Florida, 33064, United States

Location

Adverum Clinical Site

Reno, Nevada, 89502, United States

Location

Adverum Clinical Site

Philadelphia, Pennsylvania, 19107, United States

Location

Adverum Clinical Site

West Columbia, South Carolina, 29169, United States

Location

Adverum Clinical Site

Nashville, Tennessee, 37203, United States

Location

Adverum Clinical Site

Abilene, Texas, 79606, United States

Location

Adverum Clinical Site

Austin, Texas, 78705, United States

Location

Adverum Clinical Site

Houston, Texas, 77030, United States

Location

Adverum Clinical Site

The Woodlands, Texas, 77384, United States

Location

Adverum Clinical Site

Arecibo, 00612, Puerto Rico

Location

MeSH Terms

Conditions

Diabetic Retinopathy; Blindness; Retinal Diseases; Eye Diseases

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Vision Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Although this study was initiated as a randomized, double-masked study, the Sponsor and the independent data monitoring committee agreed to unmask the study following an ocular suspected unexpected serious adverse reaction (SUSAR) of Hypotony and concerns regarding the appropriate management of ocular inflammation and hypotony. All participants had reached the 12-week assessment at the time of unmasking.

Results Point of Contact

• Title: Study Medical Director
• Organization: Adverum Biotechnologies

clinicaltrials@adverum.com

650-656-9323

Study Officials

• INFINITY Medical Monitor, MD

  Adverum Biotechnologies, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 5, 2020
• Study Start: May 28, 2020
• Primary Completion: November 22, 2022
• Study Completion: June 14, 2023
• Last Updated: July 10, 2025
• Results First Posted: July 10, 2025

Record last verified: 2025-06

Locations

PR (1); US (13)