Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2)

Central Retinal Vein Occlusion Clinical Trial

— SCORE2  

Official title:

Study of COmparative Treatments for REtinal Vein Occlusion 2 [SCORE2]: a Multicenter, Prospective, Randomized Non-inferiority Trial of Eyes With Macular Edema Secondary to Central Retinal Vein Occlusion, Comparing Intravitreal Bevacizumab Every 4 Weeks With Intravitreal Aflibercept Every 4 Weeks.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01969708
• Other study ID #: SCORE2
• Secondary ID: U10EY023529U10EY
• Status: Completed
• Phase: Phase 3
• Start date: September 2014
• Est. completion date: March 2021

Study information

• Verified date: June 2021
• Source: The Emmes Company, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

SCORE2 is a multicenter, prospective, randomized, phase III clinical trial in which all participants enrolled will be followed for up to 2.5 years. SCORE2 is designed as a non-inferiority trial, with study eyes randomized to intravitreal bevacizumab (1.25 mg) every 4 weeks vs. intravitreal aflibercept (2.0 mg) every 4 weeks. SCORE2 aims to determine if bevacizumab is non-inferior to aflibercept for the treatment of macular edema associated with central retinal vein occlusion (CRVO), with the primary outcome of visual acuity measured at Month 6.

Description:

The primary objective of SCORE2 is to test for non-inferiority based on mean change from baseline in visual acuity letter score at Month 6 for eyes randomized to intravitreal bevacizumab every 4 weeks compared with eyes randomized to intravitreal aflibercept every 4 weeks using a non-inferiority margin of 5 letters.

Secondary objectives of SCORE2 are to:

• compare the bevacizumab and the aflibercept groups with regards to central retinal thickness, as measured with spectral domain optical coherence tomography (SD-OCT), at Month 6 and change between baseline and Month 6;

• assess Month 12 visual acuity and SD-OCT outcomes associated with different dosing strategies after Month 6 in participants who respond well to treatment;

• assess Month 12 visual acuity and SD-OCT outcomes associated with alternative treatment strategies after Month 6 in participants who respond poorly to treatment;

• compare area of retinal ischemia and rates of neovascular complications of CRVO in the bevacizumab vs. aflibercept groups;

• add to our knowledge of the safety profile of these anti-vascular endothelial growth factor (VEGF) medications in the setting of eyes with macular edema secondary to CRVO;

• conduct a cost effectiveness analysis comparing intravitreal bevacizumab to intravitreal aflibercept to assess the economic implications from a payor perspective using decision analytic methods.

Other exploratory aims of SCORE2 are to:

• investigate the correlation of features identified through SD-OCT segmentation analysis, such as the inner segment-outer segment (IS-OS) junction (also known as the ellipsoid zone), with such characteristics as visual acuity and central retinal thickness;

• investigate the correlation of area of peripheral retinal nonperfusion from widefield fluorescein angiography with visual acuity and central retinal thickness, and the prognostic value of baseline peripheral and central retina perfusion status in predicting disease course and treatment responsiveness;

• investigate the correlation of features on adaptive optics imaging with such characteristics as visual acuity and central retinal thickness.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 362
• Est. completion date: March 2021
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants must have center-involved macular edema secondary to CRVO. Eyes may be enrolled as early as the time of diagnosis of the macular edema. The definition of CRVO used in SCORE will also be used for the purposes of SCORE2: a CRVO is defined as an eye that has retinal hemorrhage or other biomicroscopic evidence of retinal vein occlusion (e.g., telangiectatic capillary bed) and a dilated venous system (or previously dilated venous system) in all 4 quadrants.

• Due to the similarities of a hemiretinal vein occlusion (HRVO) to CRVO,HRVO will be classified as CRVO for the purposes of this clinical trial. Eyes classified as having a HRVO will be limited to no more than 25% of the planned sample size. A HRVO is defined as an eye that has retinal hemorrhage or other biomicroscopic evidence of retinal vein occlusion (e.g. telangiectatic capillary bed) and a dilated venous system (or previously dilated venous system) in 5 or more clock hours but less than all 4 quadrants. Typically, a HRVO is a retinal vein occlusion that involves 2 altitudinal quadrants.

• E-Early Treatment Diabetic Retinopathy Study (ETDRS)visual acuity score of greater than or equal to 19 letters (approximately 20/400) and less than or equal to 73 letters (approximately 20/40) by the ETDRS visual acuity protocol. The investigator must believe that a study eye with visual acuity between 19 and 33 letters is perfused.

• Retinal thickness on SD-OCT measurement, defined as central subfield thickness of 300 µm or greater. If the SD-OCT measurement is taken from a Heidelberg Spectralis Machine, the central subfield thickness should be 320 µm or greater.

• Media clarity, pupillary dilation and participant cooperation sufficient for adequate fundus photographs.

Exclusion Criteria:

• A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., chronic alcoholism or drug abuse, personality disorder or use of major tranquilizers indicating difficulty in long term follow-up, likelihood of survival of less than 12 months).

• Participation in an investigational trial within 30 days of study entry that involved treatment with any drug that has not received regulatory approval at time of study entry.

• History of allergy to any anti-VEGF agent, corticosteroid, or component of the delivery vehicle.

• The participant will be moving out of the area of the clinical site to an area not covered by another clinical site during the 12 months of the study.

• Positive urine pregnancy test: all women of childbearing potential (those who are pre-menopausal and not surgically sterilized) may participate only if they have a negative urine pregnancy test, and if they do not intend to become pregnant during the timeframe of the study. Women who are sexually active with a male partner must agree to use at least one of the following birth control methods: hormonal therapy such as oral, implantable or injectable chemical contraceptives; mechanical therapy such as spermicide in conjunction with a barrier such as a condom or diaphragm; intrauterine device (IUD); or surgical sterilization of partner.

• Women who are breast-feeding.

• Examination evidence of vitreoretinal interface disease (e.g., vitreomacular traction, epiretinal membrane), either on clinical examination or OCT thought to be contributing to macular edema.

• An eye that, in the investigator's opinion, would not benefit from resolution of macular edema such as eyes with foveal atrophy, dense pigmentary changes or dense subfoveal hard exudates.

• Presence of an ocular condition that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., age-related macular degeneration, uveitis or other ocular inflammatory disease, neovascular glaucoma, iris neovascularization, Irvine-Gass Syndrome, prior macula-off rhegmatogenous retinal detachment).

• Presence of a substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., a 20/40 cataract).

• History of laser photocoagulation for macular edema within 3 months prior to randomization.

• History of intravitreal corticosteroid within 4 months of randomization.

• Intravitreal anti-VEGF injection within 2 months of randomization. Note: Enrollment will be limited to no more than 25% of the planned sample size with any history of anti-VEGF treatment. Once this number of eyes has been enrolled, any history of anti-VEGF treatment will be an exclusion criterion. For enrollment of study eyes with prior intravitreal anti-VEGF agents, in the opinion of the investigator, the treatment response to prior anti-VEGF treatment must be either incomplete or the study eye had developed recurrent CRVO-associated macular edema, such that the study eye would benefit from additional anti-VEGF treatment.

• History of peribulbar or retrobulbar corticosteroid use for any reason within 2 months prior to randomization.

• History of panretinal scatter photocoagulation (PRP) or sector laser photocoagulation within 3 months prior to randomization or anticipated within the next 3 months following randomization.

• History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within 4 months prior to randomization or anticipated within the next 6 months following randomization.

• History of yttrium aluminum garnet (YAG) capsulotomy performed within 2 months prior to randomization.

• Aphakia.

• Presence of an anterior chamber intraocular lens

• Examination evidence of external ocular infection, including conjunctivitis, chalazion or significant blepharitis.

• History of macular detachment.

• Examination evidence of any diabetic retinopathy.

Related Conditions & MeSH terms

• Central Retinal Vein Occlusion
• Retinal Vein Occlusion

Intervention

Drug:
• aflibercept

• bevacizumab

Locations

Country	Name	City	State
United States	Retina Research Institute of Texas	Abilene	Texas
United States	Texas Retina Associates	Arlington	Texas
United States	Emory University Eye Center	Atlanta	Georgia
United States	Southeast Retina Center	Augusta	Georgia
United States	The Retina Research Center	Austin	Texas
United States	Elman Retina Group, PA	Baltimore	Maryland
United States	Charlotte Eye Ear Nose & Throat Associates, P.A.	Charlotte	North Carolina
United States	The Retina Group of Washington	Chevy Chase	Maryland
United States	Illinois Eye and Ear Infirmary UIC Dept. of Ophthalmology	Chicago	Illinois
United States	Retina Associates of Cleveland, Inc.	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Texas Retina Associates	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	The Retina Group of Washington	Fairfax	Virginia
United States	Carolinas Centers for Sight, PC	Florence	South Carolina
United States	Retina Group of Florida	Fort Lauderdale	Florida
United States	National Ophthalmic Research Institute	Fort Myers	Florida
United States	Elman Retina Group, P.A.	Glen Burnie	Maryland
United States	Cumberland Valley Retina Consultants	Hagerstown	Maryland
United States	Charlotte Eye Ear Nose & Throat Associates, P.A.	Houston	Texas
United States	Retina & Vitreous of Texas	Houston	Texas
United States	Retina Consultants of Houston, PA	Houston	Texas
United States	Thomas A. Ciulla, MD, PC	Indianapolis	Indiana
United States	TLC Eyecare & Laser Centers	Jackson	Michigan
United States	University of Florida, Dept of Ophthalmology	Jacksonville	Florida
United States	Southeastern Retina Associates, PC	Knoxville	Tennessee
United States	Florida Retina Consultants	Lakeland	Florida
United States	Retina Consultants of Nevada	Las Vegas	Nevada
United States	Delaware Valley Retina Associates	Lawrenceville	New Jersey
United States	Sabates Eye Centers	Leawood	Kansas
United States	Retina Associates of Kentucky	Lexington	Kentucky
United States	University of Kentucky	Lexington	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	Georgia Retina, P.C.	Marietta	Georgia
United States	Valley Retina Institute, PA	McAllen	Texas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	VitreoRetinal Surgery	Minneapolis	Minnesota
United States	Retina Vitreous Consultants	Monroeville	Pennsylvania
United States	Northern California Retina Vitreous Associates	Mountain View	California
United States	Tennessee Retina, PC	Nashville	Tennessee
United States	Vanderbilt Eye Institute	Nashville	Tennessee
United States	NJ Retina	New Brunswick	New Jersey
United States	New England Retina Associates	New London	Connecticut
United States	New York Eye and Ear Infirmary	New York	New York
United States	East Bay Retina Consultants, Inc.	Oakland	California
United States	Dean McGee Eye Institute	Oklahoma City	Oklahoma
United States	UNMC Truhlsen Eye Institute	Omaha	Nebraska
United States	Paducah Retinal Center	Paducah	Kentucky
United States	Southern California Desert Retina Consultants	Palm Desert	California
United States	Scheie Eye Institute	Philadelphia	Pennsylvania
United States	Retinal Consultants of AZ	Phoenix	Arizona
United States	Elman Retina Group, P.A.	Pikesville	Maryland
United States	Casey Eye Institute / OHSU	Portland	Oregon
United States	Retina Northwest, PC	Portland	Oregon
United States	Black Hills Regional Eye Institute	Rapid City	South Dakota
United States	Mayo Clinic	Rochester	Minnesota
United States	Retina Associates of Western New York	Rochester	New York
United States	University of Rochester Flaum Eye Institute	Rochester	New York
United States	Retinal Consultants Medical Group, Inc.	Sacramento	California
United States	University of California Davis, Medical Center	Sacramento	California
United States	The Retina Institute	Saint Louis	Missouri
United States	Medical Center Ophthalmology Associates	San Antonio	Texas
United States	Retinal Consultants of San Antonio	San Antonio	Texas
United States	University of California, San Francisco	San Francisco	California
United States	Sarasota Retina Institute	Sarasota	Florida
United States	Retina Associates, PA	Shawnee Mission	Kansas
United States	Charlotte Eye Ear Nose & Throat Associates, P.A.	Statesville	North Carolina
United States	Retina Vitreous Surgeon of CNY, PC	Syracuse	New York
United States	Retina Centers, P.C.	Tucson	Arizona
United States	Palmetto Retina Center	West Columbia	South Carolina
United States	Center for Retina and Macular Disease	Winter Haven	Florida
United States	Florida Retina Consultants	Winter Haven	Florida

Sponsors (4)

Lead Sponsor	Collaborator
The Emmes Company, LLC	Milton S. Hershey Medical Center, National Eye Institute (NEI), University of Wisconsin, Madison

Country where clinical trial is conducted

United States, 

References & Publications (12)

Etheridge T, Blodi B, Oden N, Van Veldhuisen P, Scott IU, Ip MS, Mititelu M, Domalpally A. Spectral Domain OCT Predictors of Visual Acuity in the Study of COmparative Treatments for REtinal Vein Occlusion 2: SCORE 2 Report 15. Ophthalmol Retina. 2020 Dec 26. pii: S2468-6530(20)30503-0. doi: 10.1016/j.oret.2020.12.016. [Epub ahead of print] — View Citation

Etheridge T, Dobson ETA, Wiedenmann M, Oden N, VanVeldhuisen P, Scott IU, Ip MS, Eliceiri KW, Blodi BA, Domalpally A. Ellipsoid Zone Defects in Retinal Vein Occlusion Correlates With Visual Acuity Prognosis: SCORE2 Report 14. Transl Vis Sci Technol. 2021 Mar 1;10(3):31. doi: 10.1167/tvst.10.3.31. — View Citation

Etheridge T, Dobson ETA, Wiedenmann M, Papudesu C, Scott IU, Ip MS, Eliceiri KW, Blodi BA, Domalpally A. A semi-automated machine-learning based workflow for ellipsoid zone analysis in eyes with macular edema: SCORE2 pilot study. PLoS One. 2020 Apr 30;15(4):e0232494. doi: 10.1371/journal.pone.0232494. eCollection 2020. — View Citation

Hendrick A, VanVeldhuisen PC, Scott IU, King J, Blodi BA, Ip MS, Khurana RN, Oden NL; SCORE2 Investigator Group. SCORE2 Report 13: Intraretinal Hemorrhage Changes in Eyes With Central or Hemiretinal Vein Occlusion Managed With Aflibercept, Bevacizumab or Observation. Secondary Analysis of the SCORE and SCORE2 Clinical Trials. Am J Ophthalmol. 2021 Feb;222:185-193. doi: 10.1016/j.ajo.2020.08.030. Epub 2020 Aug 20. — View Citation

Ip MS, Oden NL, Scott IU, VanVeldhuisen PC, Blodi BA, Ghuman T, Baker CW; SCORE2 Investigator Group. Month 12 Outcomes After Treatment Change at Month 6 Among Poor Responders to Aflibercept or Bevacizumab in Eyes With Macular Edema Secondary to Central or Hemiretinal Vein Occlusion: A Secondary Analysis of the SCORE2 Study. JAMA Ophthalmol. 2019 Mar 1;137(3):281-287. doi: 10.1001/jamaophthalmol.2018.6111. — View Citation

Peterson JS, Rockwell K Jr, Scott IU, Ip MS, VanVeldhuisen PC, Blodi BA; SCORE2 Investigator Group. LONG-TERM PHYSICAL STABILITY, STERILITY, AND ANTI-VEGF BIOACTIVITY OF REPACKAGED BEVACIZUMAB IN 2-ML GLASS VIALS. Retina. 2019 Sep;39(9):1802-1809. doi: 10.1097/IAE.0000000000002212. — View Citation

Scott IU, Figueroa MJ, Oden NL, Ip MS, Blodi BA, VanVeldhuisen PC; SCORE2 Investigator Group. SCORE2 Report 5: Vision-Related Function in Patients With Macular Edema Secondary to Central Retinal or Hemiretinal Vein Occlusion. Am J Ophthalmol. 2017 Dec;184:147-156. doi: 10.1016/j.ajo.2017.10.008. Epub 2017 Oct 23. — View Citation

Scott IU, VanVeldhuisen PC, Ip MS, Blodi BA, Oden NL, Altaweel M, Berinstein DM; SCORE2 Investigator Group. Comparison of Monthly vs Treat-and-Extend Regimens for Individuals With Macular Edema Who Respond Well to Anti-Vascular Endothelial Growth Factor Medications: Secondary Outcomes From the SCORE2 Randomized Clinical Trial. JAMA Ophthalmol. 2018 Apr 1;136(4):337-345. doi: 10.1001/jamaophthalmol.2017.6843. — View Citation

Scott IU, VanVeldhuisen PC, Ip MS, Blodi BA, Oden NL, Awh CC, Kunimoto DY, Marcus DM, Wroblewski JJ, King J; SCORE2 Investigator Group. Effect of Bevacizumab vs Aflibercept on Visual Acuity Among Patients With Macular Edema Due to Central Retinal Vein Occ — View Citation

Scott IU, VanVeldhuisen PC, Ip MS, Blodi BA, Oden NL, Figueroa M, Dugel PU; SCORE2 Investigator Group. SCORE2 Report 2: Study Design and Baseline Characteristics. Ophthalmology. 2017 Feb;124(2):245-256. doi: 10.1016/j.ophtha.2016.09.038. Epub 2016 Nov 15. — View Citation

Scott IU, VanVeldhuisen PC, Ip MS, Blodi BA, Oden NL, Figueroa M; SCORE2 Investigator Group. SCORE2 Report 1: Techniques to Optimize Recruitment in Phase III Clinical Trials of Patients With Central Retinal Vein Occlusion. Am J Ophthalmol. 2016 Oct;170:25-31. doi: 10.1016/j.ajo.2016.07.011. Epub 2016 Jul 19. — View Citation

Scott IU, VanVeldhuisen PC, Ip MS, Blodi BA, Oden NL, King J, Antoszyk AN, Peters MA, Tolentino M; SCORE2 Investigator Group. Baseline Factors Associated With 6-Month Visual Acuity and Retinal Thickness Outcomes in Patients With Macular Edema Secondary to Central Retinal Vein Occlusion or Hemiretinal Vein Occlusion: SCORE2 Study Report 4. JAMA Ophthalmol. 2017 Jun 1;135(6):639-649. doi: 10.1001/jamaophthalmol.2017.1141. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity Letter Score at Month 6	The primary analysis is based on observed data at 6 months. The measure is calculated by subtracting the baseline visual acuity letter score from the month 6 visual acuity letter score. The participant is refracted for best corrected vision, and then reads single letters on an electronic visual acuity tester at a 3 meter distance according to a specific algorithm. A letter score is provided that ranges from 0 (unable to ready any letters) to 100. A visual acuity letter score of 85 corresponds to a visual acuity of 20/20 as a Snellen equivalent.	Month 0 to 6
Secondary	Number of Study Eyes With Gain of =15 Letters in Visual Acuity Letter Score at Month 6	The measure is the number of study eyes that gained at least 15 letters in their visual acuity letter score at month 6	Month 0 to 6
Secondary	Number of Study Eyes With Visual Acuity Letter Score of 70 or Better at Month 6	The measure is the number of study eyes with a visual acuity letter score of 70 (Snellen equivalent of 20/40) or better at month 6	Month 0 to 6
Secondary	Mean Spectral-domain Optical Coherence Tomography Central Subfield Thickness	The measure is the mean central subfield thickness at month 6 measured by spectral-domain optical coherence tomography	Month 0 to 6
Secondary	Mean Change From Baseline in Spectral Domain Optical Coherence Tomography Central Subfield Thickness at Month 6	The measure is calculated by subtracting the baseline central subfield thickness from the month 6 central subfield thickness	Month 0 to 6
Secondary	Number of Study Eyes With Central Subfield Thickness <300 µm, no Subretinal Fluid, no Intraretinal Fluid, and no Cystoid Spaces	The measure is the number of study eyes with central subfield thickness <300 µm, no subretinal fluid, no intraretinal fluid, and no cystoid spaces at month 6	Month 0 to 6

External Links

•   SCORE2 Web Site