NEWTON: Aflibercept Injection for Previously Treated Macular Edema Associated With Central Retinal Vein Occlusions (NEWTON)

NEWTON: A Single-center Open Label Study Evaluating Intravitreal Aflibercept Injection (IAI) for Previously Treated Macular Edema Associated With Central Retinal Vein Occlusions

The purpose of the study is to determine the effect of Intravitreal Aflibercept Injection (IAI) on previously treated Central Retinal Vein Occlusions (CRVOs) with other Anti-VEGF agents.

Study Overview

• Status: Completed
• Conditions: Macular Edema With Central Retinal Vein Occlusions
• Intervention / Treatment: Drug: Aflibercept (2.0 mg)

Detailed Description

This prospective, open-label, single-center, nonrandomized, investigator-sponsored clinical study seeks to investigate the visual outcomes of a treat and extend dosing regimen of intravitreal aflibercept injection for macular edema following CRVO. All patients will receive IAI 2 mg at baseline and Week 4. If the pre-defined extension criteria are met at the 4-week visit, and at any follow up visit, the patient will receive a mandated treatment, and the next visit will be extended by two weeks. If the extension criteria are not met on a follow-up visit, the treatment interval will be continued to be reduced by 1 week. If criteria are still not met despite treatment at the reduced interval, treatment will be administered as usual and follow up interval will continue to be reduced by 1 week until the criteria are met or a 4-week interval is reached. Treatment of IAI is rendered at every visit.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients aged 18 and above with documented history of center-involved macular edema secondary to CRVO.
• Patients must have received treatment for at least 6 months before baseline, with 3 initial loading doses, and evidence of recurrence of edema when extended beyond 4 weeks.
• Protocol refracted ETDRS BCVA of 20/25 to 20/320 (73-24 letters).
• Willing and able to comply with clinic visits and study-related procedures.
• Provide signed informed consent.

Exclusion Criteria:

• Prior panretinal or macular laser photocoagulation
• Previous use of intraocular corticosteroids or use of periocular corticosteroids within the 3 months prior to day 1
• Prior treatment with systemic anti-VEGF agents
• Presence of iris neovascularization
• Vitreous hemorrhage in the Study Eye
• Traction retinal detachment, or preretinal fibrosis involving the macula
• Diabetic macular edema or diabetic retinopathy, defined as eyes of diabetic patients with more than 1 microaneurysm outside the area of the vein occlusion.
• Infectious blepharitis, keratitis, scleritis, or conjunctivitis.
• Active intraocular inflammation (grade trace or above) in the study eye, or history of idiopathic or autoimmune-associated uveitis in either eye.
• Uncontrolled glaucoma in the study eye (defined as intraocular pressure equal or greater than 30mmHg despite treatment with anti-glaucoma medication)
• Concurrent eye disease in the study eye that could compromise visual acuity (e.g. advanced glaucoma, age-related macular degeneration, etc)
• Any concurrent intraocular condition in the study eye (e.g. glaucoma) that, in the opinion of the investigator, could either require medical or surgical intervention during the 52 weeks study period to prevent or treat visual loss that might result from that condition.
• 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 [IUD]; bilateral tubal ligation; vasectomy; condom plus, contraceptive sponge, foam or jelly, or diaphragm) *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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aflibercept (2.0 mg); Intravitreal Aflibercept (2.0 mg)	Drug: Aflibercept (2.0 mg); Intravitreal Aflibercept (2.0 mg); Other Names: Eylea; VEGF Trap-EYE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Intravitreal Aflibercept on Treatment Interval	Mean number of weeks between each injection where there is no macular edema	52 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Visual Acuity	Mean change in EDTRS BCVA	52 Weeks
Retinal Thickness	Mean change in Central Subfoveal Thickness by OCT	52 Weeks
Adverse Events	Incidence and severity of ocular and systemic AE's	52 Weeks
Number of Treatments	Mean number of Intravitreal Injections	52 Weeks

Collaborators and Investigators

• Sponsor: Northern California Retina Vitreous Associates
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Principal Investigator: Rahul N Khurana, MD, Northern California Retina Vitreous Associates

Publications and helpful links

General Publications

• Campochiaro PA, Brown DM, Awh CC, Lee SY, Gray S, Saroj N, Murahashi WY, Rubio RG. Sustained benefits from ranibizumab for macular edema following central retinal vein occlusion: twelve-month outcomes of a phase III study. Ophthalmology. 2011 Oct;118(10):2041-9. doi: 10.1016/j.ophtha.2011.02.038. Epub 2011 Jun 29.
• Brown DM, Heier JS, Clark WL, Boyer DS, Vitti R, Berliner AJ, Zeitz O, Sandbrink R, Zhu X, Haller JA. Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. Am J Ophthalmol. 2013 Mar;155(3):429-437.e7. doi: 10.1016/j.ajo.2012.09.026. Epub 2012 Dec 4.
• Boyer D, Heier J, Brown DM, Clark WL, Vitti R, Berliner AJ, Groetzbach G, Zeitz O, Sandbrink R, Zhu X, Beckmann K, Haller JA. Vascular endothelial growth factor Trap-Eye for macular edema secondary to central retinal vein occlusion: six-month results of the phase 3 COPERNICUS study. Ophthalmology. 2012 May;119(5):1024-32. doi: 10.1016/j.ophtha.2012.01.042. Epub 2012 Mar 21. Erratum In: Ophthalmology. 2012 Nov;119(11):2204.
• Heier JS, Campochiaro PA, Yau L, Li Z, Saroj N, Rubio RG, Lai P. Ranibizumab for macular edema due to retinal vein occlusions: long-term follow-up in the HORIZON trial. Ophthalmology. 2012 Apr;119(4):802-9. doi: 10.1016/j.ophtha.2011.12.005. Epub 2012 Feb 1.
• Khurana RN, Chang LK, Bansal AS, Palmer JD, Wu C, Wieland MR. Treat and extend regimen with aflibercept for chronic central retinal vein occlusions: 2 year results of the NEWTON study. Int J Retina Vitreous. 2019 Apr 15;5:10. doi: 10.1186/s40942-019-0159-x. eCollection 2019.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: May 25, 2013
• First Submitted That Met QC Criteria: June 5, 2013
• First Posted (Estimate): June 6, 2013

Study Record Updates

• Last Update Posted (Estimate): December 8, 2016
• Last Update Submitted That Met QC Criteria: December 7, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Bevacizumab; Ranibizumab; Eylea; CRVO; Aflibercept; Central Retinal Vein Occlusion; Macular Edema; VEGF Trap-Eye
• 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; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: NCRVA-2013-Newton-4-01