Study of Intravitreal Aflibercept Injection for Persistent CRVO-associated Macular Edema Despite Prior Anti-VEGF Therapy

Phase 4 Study of Intravitreal Aflibercept Injection for Recalcitrant Central Retinal Vein Occlusion Associated Macular Edema Despite Prior Anti-Vascular Endothelial Growth Factor (VEGF) Therapy. (ARChiMEDES)

The purpose of this study is determine the number of patients with complete resolution of macular edema secondary to central retinal vein occlusion following 6 monthly injections of Aflibercept.

Study Overview

• Status: Unknown
• Conditions: Retinal Vein Occlusion
• Intervention / Treatment: Drug: Aflibercept

Detailed Description

Twenty (20) consented participant who meet the inclusion criteria will be enrolled to be followed for 6 months. All subjects will receive monthly 2.0 mg intravitreal aflibercept injections.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina, PC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:A patient must meet the following criteria to be eligible for inclusion in the study:

• Age >18 years
• Documented macular edema following central retinal vein occlusion
• Currently receiving treatment with intravitreal anti-VEGF therapy initiated at least 3 months months previously
• Documented intravitreal treatment with ranibizumab 0.5 mg (at least 3 doses, each one month apart) or bevacizumab 1.25 mg (at least 3 doses, each one month apart)

• Presence of persistent macular edema (defined as any of the following):

  • central foveal thickness (CFT) of > 300 microns by spectral-domain OCT
  • presence of any intraretinal or subretinal fluid
  • Receipt of intravitreal anti-VEGF injections more frequently than once per month
• Willingness and ability to comply with clinic visits and study-related procedures
• Ability to provide signed informed consent

Exclusion Criteria:

• Prior vitrectomy in the study eye
• Concurrent retinal vascular disease in the study eye that could compromise visual acuity or contribute to macular edema (e.g. diabetic retinopathy, age-related macular degeneration)

• Any concurrent intraocular condition in the study eye (e.g. diabetic retinopathy, advanced glaucoma) that, in the opinion of the investigator, could either

  • require medical or surgical intervention during the 6-month study period to prevent or treat visual loss; or,
  • if allowed to progress untreated, contribute to loss of at least 2 Snellen equivalent lines of best corrected visual acuity over the 6 month study period
• Active intraocular inflammation (grade trace or above) in the study eye, or history of idiopathic or autoimmune-associated uveitis in either eye
• Current vitreous hemorrhage in the study eye
• Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
• Intraocular surgery (including cataract surgery) in the study eye within 60 days preceding baseline
• Systemic anti-VEGF treatment within the last 3 months prior to screening
• Prior intravitreal aflibercept injection in the study eye
• Macular laser photocoagulation within 4 months of screening
• Intravitreal or periocular corticosteroid within 4 months of screening
• Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥30 mmHg despite treatment with ocular antihypertensive medication)
• Allergy to fluorescein, povidone iodine (Betadine) or aflibercept
• Participation in a study of an investigational drug or device within 30 days prior to potential enrollment into the study
• Patients with cognitive dysfunction such as dementia, Alzheimer's disease or any other neuro-degenerative disorder.
• Pregnant or breast-feeding women

• Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception during the study (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 child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Aflibercept 2.0mg; Single arm - Intravitreal Aflibercept 2.0mg, 0.05 milliliters, monthly for 6 months.	Drug: Aflibercept; Monthly 2.0mg Aflibercept Intravitreal Injection; Other Names: Eylea; VEGF-Trap

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete anatomic resolution of macular edema following central retinal vein occlusion (CRVO) as measured by Optical Coherence Tomography (OCT)	From baseline to Month 6

Secondary Outcome Measures

Outcome Measure	Time Frame
Extent of reduction in macular thickness	Month 6
Extent of reduction in macular volume	Month 6
Mean change in best-corrected visual acuity (BCVA)	Month 6
Proportion of patients with gain or loss of 5, 10, and 15 letters in BCVA	Month 6
Number and severity of adverse events	6 month-period

Other Outcome Measures

Outcome Measure	Time Frame
Effect on macular leakage using fluorescein angiogram (FA)	Month 6
Effect on peripheral retinal non-perfusion	Month 6

Collaborators and Investigators

• Sponsor: Tennessee Retina
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Principal Investigator: Franco M Recchia, MD, Tennessee Retina, PC

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (ANTICIPATED): January 1, 2016
• Study Completion (ANTICIPATED): March 1, 2016

Study Registration Dates

• First Submitted: May 16, 2013
• First Submitted That Met QC Criteria: May 16, 2013
• First Posted (ESTIMATE): May 20, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): October 29, 2014
• Last Update Submitted That Met QC Criteria: October 27, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Central Retinal Vein Occlusion; Macular Edema; Retinal Vein Occlusion
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Degeneration; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Macular Degeneration; Macular Edema; Retinal Vein Occlusion; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: VGFT-OD-1313 (OTHER: Regeneron Pharmaceuticals)