Evaluation of the Retina in Patients With Non-proliferative Diabetic Retinopathy After Aflibercept Injection in the Eye

NCT04702048 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: STUDY00005589
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to specifically assess the effect of intravitreal aflibercept injections on the health of cells and the flow of blood through the retinal blood vessels by using advanced technology called adaptive optics.

Conditions

Retinopathy, Diabetic

Outcome Measures

Primary Outcomes (3)

• Mean change in photoreceptor mosaic

  Adaptive optics imaging will be used to visualize the photoreceptor cells in the eye and the number of photoreceptor cells will be quantified at baseline and 52 weeks.

  baseline to 52 weeks

• Mean change in photoreceptor cell density

  Adaptive optics imaging will be used to visualize the photoreceptor cells in the eye and the number of photoreceptor cells per square micron of image will be quantified at baseline and 52 weeks.

  baseline to 52 weeks

• Mean change in photoreceptor cell spacing

  Adaptive optics imaging will be used to visualize the photoreceptor cells in the eye and a measurement of the space between photoreceptor cells will be calculated at baseline and 52 weeks.

  baseline to 52 weeks

Secondary Outcomes (21)

• Percent of participants with any ocular adverse events

  52 weeks

• Percent of participants with a severe ocular adverse events

  52 weeks

• Percent of participants with a non-ocular adverse events

  52 weeks

• Percent of participants with a severe non-ocular adverse events

  52 weeks

• Mean change in foveal avascular zone area

  baseline to 52 weeks

Study Arms (2)

Aflibercept injection

EXPERIMENTAL

Intravitreal injection of Aflibercept

Drug: Aflibercept Injection

Sham injection

PLACEBO COMPARATOR

Empty syringe with no needle

Drug: Sham injection

Interventions

Aflibercept Injection DRUG

Patients randomized to Arm A will receive 2 mg IVT aflibercept injections every 4 weeks (Q4W) to Week 20, followed by 2-mg aflibercept injections Q8W to Week 52.

Aflibercept injection

Sham injection DRUG

Patients randomized to Arm B will receive sham intravitreal injections every 4 weeks (Q4W) to Week 20, followed by sham intravitreal injections Q8W to Week 52. Sham means eye will be numbed and a syringe with no needle will be touched to the eye.

Sham injection

Eligibility Criteria

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

You may qualify if:

• Documented Type 1 or 2 diabetes mellitus who have moderately severe to severe NPDR (DRSS levels 47 or 53) as confirmed by 2 independent physician evaluators.
• Age ≥18 years
• Willingness and the ability to provide signed informed consent, comply with clinic visits and study-related procedure, and provide Health Insurance Portability and Accountability Act authorization
• BCVA of ≥ 73 letters, inclusive (≥20/40 approximate Snellen equivalent), using the ETDRS protocol at the initial testing distance of 4 meters (see the BCVA manual for additional details) on Day 1
• Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition of good quality CFPs (including ETDRS 7 modified fields or Optos ultra-widefield image to permit grading of diabetic retinopathy and assessment of the retina) and other imaging modalities, including AOSLO.
• No center-involved macular edema (defined as fluid within 1000 microns of the fovea)
• HbA1c of ≤10% within 2 months prior to the first injection visit date
• For men\* and women\*\* of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods that result in a failure rate of \<1% per year during the treatment period and for at least 3 months after the final dose of study treatment. Adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly. Contraception is not required for men with documented vasectomy. Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

You may not qualify if:

• Presence of DME threatening the center of the macula (within 1,000 microns of the foveal center) in the study eye
• Evidence of retinal neovascularization on clinical examination or FA
• Any prior focal or grid laser photocoagulation (within 1,000 microns of the foveal center) or any prior PRP in the study eye
• Any prior systemic anti-VEGF treatment or IVT anti-VEGF treatment in the study eye
• Any prior intraocular steroid injection in the study eye
• History of vitreoretinal surgery in the study eye
• Intraocular pressure (IOP) ≥25 mm Hg in the study eye
• Evidence of active infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye
• Any intraocular inflammation or infection in either eye within 3 months of the screening visit
• Current Anterior segment neovascularization, vitreous hemorrhage, or tractional retinal detachment visible at the screening assessments in the study eye
• Ocular media of insufficient quality to obtain fundus and optical coherence tomography (OCT), and adaptive optics images in the study eye
• Hemoglobin A1c (HbA1c) \>12%, or if HbA1c is ≤12%, diabetes mellitus is uncontrolled in the opinion of the investigator
• Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the patient beyond what is to be expected from standard procedures of IVT injections, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety
• Uncontrolled blood pressure (defined as systolic \>160 mm Hg or diastolic \>95 mm Hg while patient is sitting)
• History of cerebrovascular accident or myocardial infarction within 6 months of day 1

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

Flaum Eye Institute, University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

MeSH Terms

Conditions

Diabetic Retinopathy

Interventions

aflibercept; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 8, 2021
• Study Start: February 1, 2021
• Primary Completion: February 1, 2024
• Study Completion: February 1, 2024
• Last Updated: May 5, 2021

Record last verified: 2021-04

Locations

US (1)