Clinical trial NCT04418427: ADVM-022 Intravitreal Gene Therapy for DME
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]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Adverum Biotechnologies, Inc.
Sponsor class: INDUSTRY
First posted: 2020-06-05
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to worsening of DME disease activity in the study eye.
timeFrame: 96 weeks
Secondary outcomes:
measure: Incidence and severity of ocular and non-ocular adverse events (AEs)
timeFrame: 96 weeks
measure: Change from Baseline in central subfield thickness (CST) and macular volume over time measured by SD-OCT
timeFrame: 96 weeks
measure: Change from Baseline in BCVA over time
timeFrame: 96 weeks
measure: Frequency of rescue aflibercept (2 mg IVT) in the study eye over time during the study
timeFrame: 96 weeks
measure: Incidence of improvement in DRSS score over time
timeFrame: 96 weeks
measure: Incidence of worsening in DRSS score over time
timeFrame: 96 weeks
measure: Occurrence of vision threatening complication over time
timeFrame: 96 weeks
measure: Incidence of CST <300 μm over time through Week 48
timeFrame: 96 weeks
measure: Incidence of clinically significant findings via physical examinations, ocular examinations, imaging, and laboratory evaluation
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Adverum Clinical Site
state: Arizona
city: Bakersfield
country: United States
facility: Adverum Clinical Site
state: California
city: Beverly Hills
country: United States
facility: Adverum Clinical Site
state: California
city: Golden
country: United States
facility: Adverum Clinical Site
state: Colorado
city: Deerfield Beach
country: United States
facility: Adverum Clinical Site
state: Florida
city: Reno
country: United States
facility: Adverum Clinical Site
state: Nevada
city: Philadelphia
country: United States
facility: Adverum Clinical Site
state: Pennsylvania
city: West Columbia
country: United States
facility: Adverum Clinical Site
state: South Carolina
city: Nashville
country: United States
facility: Adverum Clinical Site
state: Tennessee
city: Abilene
country: United States
facility: Adverum Clinical Site
state: Texas
city: Austin
country: United States
facility: Adverum Clinical Site
state: Texas
city: Houston
country: United States
facility: Adverum Clinical Site
state: Texas
city: The Woodlands
country: United States
facility: Adverum Clinical Site
state: Texas
city: Arecibo
country: Puerto Rico
facility: Adverum Clinical Site
Study officials:
affiliation: Adverum Biotechnologies, Inc.
name: INFINITY Medical Monitor, MD
role: STUDY_CHAIR
References: