ADVM-022 Intravitreal Gene Therapy for DME

Diabetic Retinopathy Clinical Trial

— INFINITY  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04418427
• Other study ID #: ADVM-022-04
• Status: Completed
• Phase: Phase 2
• Start date: May 28, 2020
• Est. completion date: November 22, 2022

Study information

• Verified date: August 2023
• Source: Adverum Biotechnologies, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: November 22, 2022
• Est. primary completion date: November 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Diabetic Retinopathy
• Edema
• Macular Edema
• Retinal Diseases

Intervention

Biological:
• 6E11 vg/eye of ADVM-022
ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept
• 2E11 vg/eye of ADVM-022
ADVM-022 (AAV.7m8-aflibercept) is a recombinant, replication-deficient adeno-associated virus (AAV.7m8) gene therapy vector carrying a coding sequence for aflibercept
• Aflibercept
Commercially available Active Comparator

Locations

Country	Name	City	State
Puerto Rico	Adverum Clinical Site	Arecibo
United States	Adverum Clinical Site	Abilene	Texas
United States	Adverum Clinical Site	Austin	Texas
United States	Adverum Clinical Site	Bakersfield	California
United States	Adverum Clinical Site	Beverly Hills	California
United States	Adverum Clinical Site	Deerfield Beach	Florida
United States	Adverum Clinical Site	Golden	Colorado
United States	Adverum Clinical Site	Houston	Texas
United States	Adverum Clinical Site	Nashville	Tennessee
United States	Adverum Clinical Site	Philadelphia	Pennsylvania
United States	Adverum Clinical Site	Phoenix	Arizona
United States	Adverum Clinical Site	Reno	Nevada
United States	Adverum Clinical Site	The Woodlands	Texas
United States	Adverum Clinical Site	West Columbia	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Adverum Biotechnologies, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to worsening of DME disease activity in the study eye.	Time to worsening of DME disease activity in the study eye.	96 weeks
Secondary	Incidence and severity of ocular and non-ocular adverse events (AEs)	Incidence and severity of ocular and non-ocular adverse events (AEs)	96 weeks
Secondary	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	96 weeks
Secondary	Change from Baseline in BCVA over time	Change from Baseline in BCVA over time	96 weeks
Secondary	Frequency of rescue aflibercept (2 mg IVT) in the study eye over time during the study	Frequency of rescue aflibercept (2 mg IVT) in the study eye over time during the study	96 weeks
Secondary	Incidence of improvement in DRSS score over time	Incidence of improvement in DRSS score over time	96 weeks
Secondary	Incidence of worsening in DRSS score over time	Incidence of worsening in DRSS score over time	96 weeks
Secondary	Occurrence of vision threatening complication over time	Occurrence of vision threatening complication over time	96 weeks
Secondary	Incidence of CST <300 µm over time through Week 48	Incidence of CST <300 µm over time through Week 48	96 weeks
Secondary	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	96 weeks