lntravitreal Aflibercept
`Injection (IAI)
`(Baseline to Week 24)
`
`Sham Treatment
`(Baseline to Week 24)
`
`IAI to IAI (Week 24 to
`Week 100)
`
`Sham Treatment to
`IAI (Week 24 to Week
`100)
`
`Iris neovascularisation A [21*
`
`Lacrimation increased A [21*
`
`0/114 (0%)
`
`0/114 (0%)
`
`Macular oedema A [21*
`
`0/114 (0%)
`
`Maculopathy A [21*
`
`10/114 (8.77%)
`
`Optic disc vascular disorder A [21*
`
`8/114 (7.02%)
`
`Retinal exudates A l21*
`
`7/114 (6.14%)
`
`Retinal haemorrhage A l11*
`
`Retinal pigment epitheliopathy A [21*
`
`0/114 (0%)
`
`0/114 (0%)
`
`4/74 (5.41%)
`
`0/7 4 (0%)
`
`0/7 4 (0%)
`
`0/7 4 (0%)
`
`0/7 4 (0%)
`
`0/7 4 (0%)
`
`0/7 4 (0%)
`
`0/7 4 (0%)
`
`0/110(0%)
`
`0/110(0%)
`
`20/110 (18.18%)
`
`6/110 (5.45%)
`
`0/60 (0%)
`
`4/60 (6.67%)
`
`0/60 (0%)
`
`0/60 (0%)
`
`6/110 (5.45%)
`
`5/60 (8.33%)
`
`0/110(0%)
`
`5/60 (8.33%)
`
`6/110 (5.45%)
`
`4/60 (6.67%)
`
`0/110(0%)
`
`12/60 (20%)
`
`Retinal vascular disorder A [21*
`
`6/114 (5.26%)
`
`4/74 (5.41%)
`
`8/110 (7.27%)
`
`0/60 (0%)
`
`Visual acuity reduced A [21*
`
`7/114 (6.14%)
`
`12/74 (16.22%)
`
`27/110 (24.55%)
`
`8/60 ( 13.33%)
`
`Vitreous detachment A [21*
`
`0/114 (0%)
`
`5/7 4 (6.76%)
`
`8/110 (7.27%)
`
`Vitreous floaters A [21*
`
`6/114 (5.26%)
`
`0/7 4 (0%)
`
`0/110(0%)
`
`Infections and infestations
`
`Influenza A*
`
`0/114 (0%)
`
`0/7 4 (0%)
`
`7/110 (6.36%)
`
`Nasopharyngitis A*
`
`0/114 (0%)
`
`4/74 (5.41%)
`
`6/110 (5.45%)
`
`Upper respiratory tract infection A*
`
`6/114 (5.26%)
`
`0/7 4 (0%)
`
`6/110 (5.45%)
`
`0/60 (0%)
`
`0/60 (0%)
`
`0/60 (0%)
`
`0/60 (0%)
`
`0/60 (0%)
`
`Investigations
`
`Blood pressure systolic increased A*
`
`0/114 (0%)
`
`0/7 4 (0%)
`
`0/110(0%)
`
`4/60 (6.67%)
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3966
`
`

`

`lntravitreal Aflibercept
`Injection (IAI)
`(Baseline to Week 24)
`
`Sham Treatment
`(Baseline to Week 24)
`
`IAI to IAI (Week 24 to
`Week 100)
`
`Sham Treatment to
`IAI (Week 24 to Week
`100)
`
`Blood urine present A*
`
`0/114 (0%)
`
`lntraocular pressure increased A [11*
`
`0/114 (0%)
`
`Protein urine present A*
`
`0/114 (0%)
`
`0/7 4 (0%)
`
`0/7 4 (0%)
`
`0/7 4 (0%)
`
`0/110(0%)
`
`0/110(0%)
`
`0/110(0%)
`
`4/60 (6.67%)
`
`4/60 (6.67%)
`
`5/60 (8.33%)
`
`Vascular disorders
`
`Hypertension A*
`
`10/114 (8.77%)
`
`4/7 4 (5.41 % )
`
`13/110 (11.82%)
`
`9/60(15%)
`
`* Indicates events were collected by non~systematic methods.
`A Term from vocabulary, MedDRA Version 13.1
`[1] Ocular AE Fellow Eye
`[2] Ocular AE Study Eye
`
`[Not specified]
`
`More Information ............................................................................................................................................................................................................................................................................................................................ ..
`
`Certain Agreements:
`
`Principal Investigators are NOT employed by the organization sponsoring the study.
`
`There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the Pl's rights to discuss or
`publish trial results after the trial is completed.
`
`Results Point of Contact:
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3967
`
`

`

`Name/Official Title: Clinical Trials Administrator
`Organization: Regeneron Pharmaceuticals
`Phone: 914 847 5385
`Email: clinicaltrials@regeneron.com
`
`Scroll up io access ihe controls
`
`Scroll to Hie StudY, toQ
`
`U,S. National Library of Medicine I U.S, National Institutes of Health I U,S. Department of Health & Hurmm Se1vices
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3968
`
`

`

`•
`
`U. S,National Library of Medicine
`
`History of Changes for Study: NCT00943072
`
`Vascular Endothelial Growth Factor (VEGF) Trap .. Eye: Investigation of Efficacy and Safety in Central Retinal
`Vein Occlusion (CRVO)
`
`Latest version (submitted AQril 16, 20'13) on ClinicalTrials,ggy
`
`, A study version is represented by a row in the table.
`
`, Select two study versions to compare. One each from columns A and B,
`
`11 Choose either the 11Merged 11 or 11Side-by-Side 11 comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only
`applies to the Protocol section of the study,
`
`11 Click 11Compare 11 to do the comparison and show the differences.
`
`, Select a version's Submitted Date link to see a rendering of the study for that version.
`
`, The yellow A/8 choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed,
`
`11 Hover over the 11Recruitment Status 11 to see how the study's recruitment status changed.
`
`, Study edits or deletions are displayed in ffia.
`
`, Study additions are displayed in !.w~~.n.t
`
`Study Record Versions·······················································································································································································································································-···························
`
`Version I A I B I Submitted Date
`
`Changes
`
`•''\
`l)
`
`"''\
`l.,:
`
`(\
`\)
`
`•'''\
`l.,:
`
`2
`
`JulY. 20, 2009 None (earliest Version on record)
`
`September 3, 2009 Contacts/Locations and Study Status
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3969
`
`

`

`Version I A I B I Submitted Date I I
`(\ n
`t ... )
`
`'
`
`Changes
`
`3
`
`\'\,,/
`
`October 71 2009 Contacts/Locations and Study Status
`
`4
`
`5
`
`6
`
`7
`
`8
`
`t\
`\'
`.. i
`
`t\
`\'
`.. i
`
`December 31 2009 Study Status
`
`t'\
`\)
`
`••'\
`(.,.1
`
`l'\
`\)
`
`t .. ''\
`\.i
`
`Februa1:y '18, 2010 Contacts/Locations and Study Status
`
`Julyj, 2010 Recruitment Status, Study Status and Contacts/Locations
`
`l .. "\
`\..,,l
`
`l .... '\
`
`\.l November 181 2010 Study Status
`
`t')
`\, .. l
`
`t"\
`\,.)
`
`Februa[Y 11, 2011 Study Status and Study Design
`
`''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''"''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''"''''
`
`9
`
`(\
`\.,..)
`
`(\
`\. .. )
`
`Mayj, 2011 Study Status
`
`10
`
`11
`
`•''\ l .. }
`
`•''\ l)
`
`"'\ t)
`
`"'\ t)
`
`Mayj, 2011 Study Status
`
`March 28, 2012 Sponsor/Collaboratorsl Study Status and Contacts/Locations
`
`12 @ @
`
`June 7, 2012 Recruitment Status I Study Status
`
`13
`
`.l'\
`\,i
`
`/"''\
`\ .. ,l
`
`6P.ril 161 2013 Outcome Measuresl Study Status 1 More Information I Reported Adverse Events 1 Baseline Characteristics and
`Participant Flow
`
`Comparison Format:
`
`@Merged
`0 Side-by-Side
`
`Scroll up to access the controls
`
`Study NCT00943072
`Submitted Date: June 7, 2012 (v12)
`
`Study Identification ............................................................................................................................................................................................................................................................................................................................. .
`
`Unique Protocol ID: VGFT-OD-0819
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3970
`
`

`

`Brief Title: Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Central
`Retinal Vein Occlusion (CRVO)
`
`Official Title: A Randomized, Double Masked, Controlled Phase 3 Study of the Efficacy, Safety, and Tolerability of
`Repeated lntravitreal Administration of Vascular Endothelial Growth Factor Trap-Eye in Subjects With
`Macular Edema Secondary to Central Retinal Vein Occlusion
`
`Secondary IDs:
`
`Study Status .......................................................................................................................................................................................................................................................................................................................................... .
`
`Record Verification: June 2012
`
`Overall Status: Completed
`
`Study Start: July 2009
`
`Primary Completion: October 2010 [Actual]
`
`Study Completion: April 2012 [Actual]
`
`First Submitted: July 10, 2009
`
`First Submitted that July 20, 2009
`Met QC Criteria:
`
`First Posted: July 21, 2009 [Estimate]
`
`Certification/Extension May 9, 2011
`First Submitted:
`
`Certification/Extension May 9, 2011
`First Submitted that
`Met QC Criteria:
`
`Certification/Extension May 16, 2011 [Estimate]
`First Posted:
`
`Last Update Submitted that June 7, 2012
`Met QC Criteria:
`
`Last Update Posted: June 11, 2012 [Estimate]
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3971
`
`

`

`Sponsor/Collaborators
`
`Sponsor: Regeneron Pharmaceuticals
`
`Responsible Party: Sponsor
`
`Collaborators: Bayer
`
`Oversight ·····················································································································································································································································································································································.
`
`U.S. FDA-regulated Drug:
`
`U.S. FDA-regulated Device:
`
`Data Monitoring: Yes
`
`Study Description ..................................................................... ·.····· ......................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................... .
`
`Brief Summary: This is a phase 3 study to determine the efficacy of VEGF Trap-Eye injected into the eye on vision
`function in subjects with macular edema as a consequence of central retinal vein occlusion.
`
`Detailed Description:
`
`Conditions .................................................................................................................................................................................................................................................................................................................................................... .
`
`Conditions: Macular Edema Secondary to Central Retinal Vein Occlusion
`
`Keywords: Macular edema
`Retinal vein occlusion
`CRVO
`VEGF Trap-Eye
`best-corrected visual acuity
`Regeneron
`COPERNICUS
`
`Study Design ............................................................................................................................................................................................................................................................................................................................................. .
`
`Study Type: lnterventional
`
`Primary Purpose: Treatment
`
`Study Phase: Phase 3
`
`lnterventional Study Model: Parallel Assignment
`
`Number of Arms: 2
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3972
`
`

`

`Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
`
`Allocation: Randomized
`
`Enrollment: 189 [Actual]
`
`Arms and Interventions ............................................................................................................................................................................................................................................................................................................... ..
`
`I
`
`I
`
`I
`
`Arms
`
`Assigned Interventions
`
`I Biological: VEGF Trap-Eye 2.0mg
`I Monthly intravitreal injection out to the Week 24 Primary
`I
`endpoint
`1
`I
`I Drug: Sham
`Monthly sham intravitreal injection out to Week 24 Primary
`Endpoint
`
`1
`
`1
`1
`I
`
`I Experimental: VEGF Trap-Eye
`Monthly IVT injection of VEGF Trap-Eye 2.0 mg until Week
`24 Primary Endpoint
`
`l 1
`
`
`1
`I
`\
`
`I Sham Comparator: Sham
`I Monthly Sham IVT injection until Week 24 Primary Endpoint
`I
`I
`I
`
`Outcome Measures ............................................................................................................................................................................................................................................................................................................................ .
`
`Primary Outcome Measures:
`
`1. The primary efficacy measure is improvement in visual acuity versus baseline after 6 months of treatment.
`Week 24
`
`Secondary Outcome Measures:
`
`2. Visual acuity
`Week 24
`
`3. Retinal thickness by OCT
`Week 24
`
`Eligibility ........................................................................................................................................................................................................................................................................................................................................................ ·
`
`Minimum Age: 18 Years
`
`Maximum Age:
`
`Sex: All
`
`Gender Based:
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3973
`
`

`

`Accepts Healthy Volunteers: No
`
`Criteria: Inclusion Criteria:
`
`• Subjects at least 18 years of age with center-involved macular edema secondary to CRVO with
`mean central retinal thickness ~ 250 µm on OCT
`• ETDRS best corrected visual acuity of 20/40 to 20/320 (73 to 24 letters) in the study eye
`
`Exclusion Criteria:
`
`• Previous treatment with anti-angiogenic drugs in the study eye (Pegaptanib sodium,anecortave
`acetate, bevacizumab, ranibizumab, etc.)
`• Prior panretinal laser photocoagulation or macular laser photocoagulation in the study eye
`• CRVO disease duration > 9 months from date of diagnosis
`• Previous use of intraocular corticosteroids in the study eye or use of periocular corticosteroids in
`the study eye within the 3 months prior to Day 1
`• Iris neovascularization, vitreous hemorrhage, traction retinal detachment, or preretinal fibrosis
`involving the macula in either the study eye or fellow eye
`
`Contacts/Locations ....................................................................................................................................................................................................................................................................................................................... .
`
`Study Officials: Clinical Trial Management
`Study Director
`Regeneron Pharmaceuticals
`
`Locations: United States, Arizona
`
`Phoenix, Arizona, United States, 85014
`
`Phoenix, Arizona, United States, 85020
`
`Tucson, Arizona, United States, 85704
`
`United States, California
`
`Arcadia, California, United States, 91007
`
`Beverly Hills, California, United States, 90211
`
`La Jolla, California, United States, 92037
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3974
`
`

`

`Mountain View, California, United States, 94040
`
`Oakland, California, United States, 94609
`
`Sacramento, California, United States, 95841
`
`Torrance, California, United States, 90503
`
`United States, Connecticut
`
`New London, Connecticut, United States! 06320
`
`United States, Florida
`
`Altamonte Springs, Florida, United States, 32701
`
`Fort Lauderdale, Florida 1 United States, 33334
`
`Fort Myers, Florida, United States, 33907
`
`Fort Myers! Florida, United States, 33912
`
`Miami, Florida, United States, 33143
`
`Palm Beach Gardens, Florida, United States, 3341 0
`
`Winter Haven, Florida, United States, 33880
`
`United States, Georgia
`
`Augusta 1 Georgia, United States, 30909
`
`United States, Illinois
`
`Chicago, Illinois! United States, 60612
`
`United States, Kansas
`
`Wichita, Kansas, United States 1 67214
`
`United States, Maryland
`
`Baltimore, Maryland, United States, 21209
`
`Hagerstown, Maryland, United States, 217 40
`
`Towson, Maryland, United States, 21204
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3975
`
`

`

`United States, Massachusetts
`
`Boston, Massachusetts! United States, 02114
`
`United States, Michigan
`
`Grand Rapids! Michigan, United States, 49525
`
`Jackson 1 Michigan, United States 1 48104
`
`United States, Nebraska
`
`Lincoln, Nebraska, United States, 68506
`
`United States, Nevada
`
`Las Vegas, Nevada, United States, 89135
`
`United States, New Jersey
`
`Northfield! New Jersey, United States, 08225
`
`Toms River, New Jersey1 United States 1 08755
`
`United States, New York
`
`Rochester1 New York, United States 1 14620
`
`United States, North Carolina
`
`WinstonRSalem, North Carolina, United States, 27157
`
`United States, Ohio
`
`Cleveland! Ohio, United States! 44195
`
`United States, Oklahoma
`
`Oklahoma City, Oklahoma, United States, 73104
`
`United States, Oregon
`
`Portland, Oregon, United States! 97210
`
`Salemi Oregon, United States, 97302
`
`United States, Pennsylvania
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3976
`
`

`

`Kingston, Pennsylvania, United States, 18704
`
`Pittsburgh, Pennsylvania 1 United States, 15213
`
`United States, South Carolina
`
`West Columbia, South Carolina, United States! 29169
`
`United States, South Dakota
`
`Rapid City} South Dakota, United States, 57701
`
`United States, Tennessee
`
`Nashville, Tennessee, United States, 37203
`
`United States, Texas
`
`Abilene, Texas, United States, 79606
`
`Ft Worth, Texas, United States, 76102
`
`Houston 1 Texas, United States, 77030
`
`San Antonio, Texas! United States, 78240
`
`Canada, British Columbia
`
`Vancouver, British Columbia, Canada, V5Z 3N9
`
`Victoria, British Columbia, Canada, V8V 4X3
`
`Canada, Nova Scotia
`
`Halifax, Nova Scotia, Canada, B3H 2Y9
`
`Canada, Ontario
`
`Landoni Ontario, Canada, N6A 4V2
`
`Mississauga, Ontario, Canada, L4W 1W9
`
`Toronto, Ontario, Canada, M4N 3M5
`
`Colombia, Antioquia
`
`Medellin, Antioquia, Colombia
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3977
`
`

`

`Colombia
`
`Bogota, Colombia
`
`India, A.p.
`
`Hyderabad, Ap., India, 500034
`
`India, Karnataka
`
`Bangalore, Karnataka, India, 56001 0
`
`India, West Bengal
`
`Kolkata, West Bengal, India, 700073
`
`Israel
`
`Kfar-Saba, Israel, 44281
`
`Petah Tikva, Israel, 49100
`
`Rehovot, Israel, 76100
`
`Tel Aviv, Israel, 64239
`
`IPDSharing .............................................................................................................................................................................................................................................................................................................................................. .
`
`Plan to Share I PD:
`
`References .................................................................................. ,, .............................................. ,, .............................................. ,, .............................................. ,, .............................................. ,, ............................................................... .
`
`Citations:
`
`Links:
`
`Available IPD/lnformation:
`
`Scroll up to access the controls
`
`Scroll to the Study toQ
`
`U.S National Libra1~1 of Medicine I U.S. National Institutes of Health I U.S Department of Health & Human Services
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3978
`
`

`

`•
`
`U. S,National Library of Medicine
`
`History of Changes for Study: NCT00943072
`
`Vascular Endothelial Growth Factor (VEGF) Trap .. Eye: Investigation of Efficacy and Safety in Central Retinal
`Vein Occlusion (CRVO)
`
`Latest version (submitted AQril 16, 20'13) on ClinicalTrials,ggy
`
`, A study version is represented by a row in the table.
`
`, Select two study versions to compare. One each from columns A and B,
`
`11 Choose either the 11Merged 11 or 11Side-by-Side 11 comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only
`applies to the Protocol section of the study,
`
`11 Click 11Compare 11 to do the comparison and show the differences.
`
`, Select a version's Submitted Date link to see a rendering of the study for that version.
`
`, The yellow A/8 choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed,
`
`11 Hover over the 11Recruitment Status 11 to see how the study's recruitment status changed.
`
`, Study edits or deletions are displayed in ffia.
`
`, Study additions are displayed in !.w~~.n.t
`
`Study Record Versions·······················································································································································································································································-···························
`
`Version I A I B I Submitted Date
`
`Changes
`
`•''\
`l)
`
`"''\
`l.,:
`
`(\
`\)
`
`•'''\
`l.,:
`
`2
`
`JulY. 20, 2009 None (earliest Version on record)
`
`September 3, 2009 Contacts/Locations and Study Status
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3979
`
`

`

`Version I A I B I Submitted Date I I
`(\ n
`t ... )
`
`'
`
`Changes
`
`3
`
`\'\,,/
`
`October 71 2009 Contacts/Locations and Study Status
`
`4
`
`5
`
`6
`
`7
`
`8
`
`t\
`\'
`.. i
`
`t\
`\'
`.. i
`
`December 31 2009 Study Status
`
`t'\
`\)
`
`••'\
`(.,.1
`
`l'\
`\)
`
`t .. ''\
`\.i
`
`Februa1:y '18, 2010 Contacts/Locations and Study Status
`
`Julyj, 2010 Recruitment Status, Study Status and Contacts/Locations
`
`l .. "\
`\..,,l
`
`l .... '\
`
`\.l November 181 2010 Study Status
`
`t')
`\, .. l
`
`t"\
`\,.)
`
`Februa[Y 11, 2011 Study Status and Study Design
`
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`9
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`Mayj, 2011 Study Status
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`10
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`Mayj, 2011 Study Status
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`March 28, 2012 Sponsor/Collaboratorsl Study Status and Contacts/Locations
`
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`June 7, 2012 Recruitment Status I Study Status
`
`6P.ril 161 2013 Outcome Measuresl Study Status 1 More Information I Reported Adverse Events 1 Baseline Characteristics and
`Participant Flow
`
`Comparison Format:
`
`® Merged
`0 Side-by-Side
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`Scroll up to access the controls
`
`Study NCT00943072
`Submitted Date: March 28, 2012 (v11)
`
`Study Identification ............................................................................................................................................................................................................................................................................................................................. .
`
`Unique Protocol ID: VGFT-OD-0819
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3980
`
`

`

`Brief Title: Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Central
`Retinal Vein Occlusion (CRVO)
`
`Official Title: A Randomized, Double Masked, Controlled Phase 3 Study of the Efficacy, Safety, and Tolerability of
`Repeated lntravitreal Administration of Vascular Endothelial Growth Factor Trap-Eye in Subjects With
`Macular Edema Secondary to Central Retinal Vein Occlusion
`
`Secondary IDs:
`
`Study Status .......................................................................................................................................................................................................................................................................................................................................... .
`
`Record Verification: March 2012
`
`Overall Status: Active, not recruiting
`
`Study Start: July 2009
`
`Primary Completion: October 2010 [Actual]
`
`Study Completion: April 2012 [Anticipated]
`
`First Submitted: July 10, 2009
`
`First Submitted that July 20, 2009
`Met QC Criteria:
`
`First Posted: July 21, 2009 [Estimate]
`
`Certification/Extension May 9, 2011
`First Submitted:
`
`Certification/Extension May 9, 2011
`First Submitted that
`Met QC Criteria:
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`Certification/Extension May 16, 2011 [Estimate]
`First Posted:
`
`Last Update Submitted that March 28, 2012
`Met QC Criteria:
`
`Last Update Posted: March 30, 2012 [Estimate]
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3981
`
`

`

`Sponsor/Collaborators
`
`Sponsor: Regeneron Pharmaceuticals
`
`Responsible Party: Sponsor
`
`Collaborators: Bayer
`
`Oversight ·····················································································································································································································································································································································.
`
`U.S. FDA-regulated Drug:
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`U.S. FDA-regulated Device:
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`Data Monitoring: Yes
`
`Study Description ..................................................................... ·.····· ......................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................... .
`
`Brief Summary: This is a phase 3 study to determine the efficacy of VEGF Trap-Eye injected into the eye on vision
`function in subjects with macular edema as a consequence of central retinal vein occlusion.
`
`Detailed Description:
`
`Conditions .................................................................................................................................................................................................................................................................................................................................................... .
`
`Conditions: Macular Edema Secondary to Central Retinal Vein Occlusion
`
`Keywords: Macular edema
`Retinal vein occlusion
`CRVO
`VEGF Trap-Eye
`best-corrected visual acuity
`Regeneron
`COPERNICUS
`
`Study Design ............................................................................................................................................................................................................................................................................................................................................. .
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`Study Type: lnterventional
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`Primary Purpose: Treatment
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`Study Phase: Phase 3
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`lnterventional Study Model: Parallel Assignment
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`Number of Arms: 2
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`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3982
`
`

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`Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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`Allocation: Randomized
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`Enrollment: 189 [Actual]
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`Arms and Interventions ............................................................................................................................................................................................................................................................................................................... ..
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`I
`
`I
`
`I
`
`Arms
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`Assigned Interventions
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`I Biological: VEGF Trap-Eye 2.0mg
`I Monthly intravitreal injection out to the Week 24 Primary
`I
`endpoint
`1
`I
`I Drug: Sham
`Monthly sham intravitreal injection out to Week 24 Primary
`Endpoint
`
`1
`
`1
`1
`I
`
`I Experimental: VEGF Trap-Eye
`Monthly IVT injection of VEGF Trap-Eye 2.0 mg until Week
`24 Primary Endpoint
`
`l 1
`
`
`1
`I
`\
`
`I Sham Comparator: Sham
`I Monthly Sham IVT injection until Week 24 Primary Endpoint
`I
`I
`I
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`Outcome Measures ............................................................................................................................................................................................................................................................................................................................ .
`
`Primary Outcome Measures:
`
`1. The primary efficacy measure is improvement in visual acuity versus baseline after 6 months of treatment.
`Week 24
`
`Secondary Outcome Measures:
`
`2. Visual acuity
`Week 24
`
`3. Retinal thickness by OCT
`Week 24
`
`Eligibility ........................................................................................................................................................................................................................................................................................................................................................ ·
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`Minimum Age: 18 Years
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`Maximum Age:
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`Sex: All
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`Gender Based:
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`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3983
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`

`

`Accepts Healthy Volunteers: No
`
`Criteria: Inclusion Criteria:
`
`• Subjects at least 18 years of age with center-involved macular edema secondary to CRVO with
`mean central retinal thickness ~ 250 µm on OCT
`• ETDRS best corrected visual acuity of 20/40 to 20/320 (73 to 24 letters) in the study eye
`
`Exclusion Criteria:
`
`• Previous treatment with anti-angiogenic drugs in the study eye (Pegaptanib sodium,anecortave
`acetate, bevacizumab, ranibizumab, etc.)
`• Prior panretinal laser photocoagulation or macular laser photocoagulation in the study eye
`• CRVO disease duration > 9 months from date of diagnosis
`• Previous use of intraocular corticosteroids in the study eye or use of periocular corticosteroids in
`the study eye within the 3 months prior to Day 1
`• Iris neovascularization, vitreous hemorrhage, traction retinal detachment, or preretinal fibrosis
`involving the macula in either the study eye or fellow eye
`
`Contacts/Locations ....................................................................................................................................................................................................................................................................................................................... .
`
`Study Officials: Clinical Trial Management
`Study Director
`Regeneron Pharmaceuticals
`
`Locations: United States, Arizona
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`Phoenix, Arizona, United States, 85014
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`Phoenix, Arizona, United States, 85020
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`Tucson, Arizona, United States, 85704
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`United States, California
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`Arcadia, California, United States, 91007
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`Beverly Hills, California, United States, 90211
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`La Jolla, California, United States, 92037
`
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3984
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`

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`Mountain View, California, United States, 94040
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`Oakland, California, United States, 94609
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`Sacramento, California, United States, 95841
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`Torrance, California, United States, 90503
`
`United States, Connecticut
`
`New London, Connecticut, United States! 06320
`
`United States, Florida
`
`Altamonte Springs, Florida, United States, 32701
`
`Fort Lauderdale, Florida 1 United States, 33334
`
`Fort Myers, Florida, United States, 33907
`
`Fort Myers! Florida, United States, 33912
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`Miami, Florida, United States, 33143
`
`Palm Beach Gardens, Florida, United States, 3341 0
`
`Winter Haven, Florida, United States, 33880
`
`United States, Georgia
`
`Augusta 1 Georgia, United States, 30909
`
`United States, Illinois
`
`Chicago, Illinois! United States, 60612
`
`United States, Kansas
`
`Wichita, Kansas, United States 1 67214
`
`United States, Maryland
`
`Baltimore, Maryland, United States, 21209
`
`Hagerstown, Maryland, United States, 217 40
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`Towson, Maryland, United States, 21204
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`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2008 PAGE 3985
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`

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`United States, Massachusetts
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`Boston, Massachusetts! United States, 02114
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`United States, Michigan
`
`Grand Rapids! Michigan, United States, 49525
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`Jackson 1 Michigan, United States 1 48104
`
`United States, Nebraska
`
`Lincoln, Nebraska, United States, 68506
`
`United States, Nevada
`
`Las Vegas, Nevada, United States, 89135
`
`United States, New Jersey
`
`Northfield! New Jersey, United States, 08225
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`Toms River, New Jersey1 United States 1 08755
`
`United States, New York
`
`Rochester1 New York, United States 1 14620
`
`United States, North Carolina
`
`WinstonRSalem, North Carolina, United States, 27157
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`United States, Ohio
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`Cleveland! Ohio, United States! 44195
`
`United States, Oklahoma
`
`Oklahoma City, Oklahoma, United States, 73104
`
`United States, Oregon
`
`Portland, Oregon, United States! 97210
`
`Salemi Oregon, United States, 97302
`
`United States, Pennsylvania
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`APOTEX V. REG