Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (AMD) (VIEW 2)

• ClinicalTrials.gov Identifier: NCT00637377
• Recruitment Status: Completed
• First Posted: March 18, 2008
• Results First Posted: January 23, 2012
• Last Update Posted: December 12, 2014
• Sponsor: Bayer
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: March 12, 2008
• First Posted Date: March 18, 2008
• Results First Submitted Date: December 16, 2011
• Results First Posted Date: January 23, 2012
• Last Update Posted Date: December 12, 2014
• Study Start Date: April 2008
• Actual Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 16, 2011)

Percentage of Participants Who Maintained Vision at Week 52 - Last Observation Carried Forward (LOCF) [ Time Frame: At week 52 ]

Maintenance of vision was defined as a loss of < 15 letters in the ETDRS (Early Treatment Diabetic Retinopathy Study) letter score (defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed.

• Original Primary Outcome Measures (submitted: March 17, 2008): The proportion of subjects who maintain vision at Week 52, where a subject is classified as maintaining vision if the subject has lost fewer than 15 letters on the ETDRS chart compared to baseline (ie, prevention of moderate vision loss) [ Time Frame: Week 52 ]
• Change History: Complete list of historical versions of study NCT00637377 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: December 16, 2011)

• Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS Letter Score at Week 52 - LOCF [ Time Frame: Baseline and at week 52 ]
  Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning.
• Percentage of Participants Who Gained at Least 15 Letters of Vision in the ETDRS Letter Score in the Study Eye at Week 52 - LOCF [ Time Frame: At week 52 ]
  Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed.
• Mean Change From Baseline in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score at Week 52 - LOCF [ Time Frame: Baseline and at week 52 ]
  The possible range of the NEI VFQ-25 total score is between 0 (worst possible) and 100 (best possible).
• Mean Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 52 - LOCF [ Time Frame: Baseline and at week 52 ]
  CNV area values measured in square millimeters; lower values represent better outcomes.

Original Secondary Outcome Measures (submitted: March 17, 2008)

• Mean change from baseline in BCVA as measured by ETDRS letter score at Week 52 [ Time Frame: Week 52 ]
• The proportion of subjects who gain at least 15 letters of vision at Week 52 [ Time Frame: Week 52 ]
• Mean change from baseline in total NEI VFQ-25 score at Week 52 [ Time Frame: Week 52 ]
• Mean change from baseline in CNV area at Week 52 [ Time Frame: Week 52 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (AMD)
• Official Title: A Randomized, Double Masked, Active Controlled, Phase 3 Study of the Efficacy, Safety, and Tolerability of Repeated Doses of Intravitreal VEGF Trap in Subjects With Neovascular Age-related Macular Degeneration (AMD)
• Brief Summary: This study is a phase III, double-masked, randomized, study of the efficacy and safety of VEGF Trap-Eye in patients with neovascular age-related macular degeneration. Approximately 1200 patients will be randomized in Europe, Asia, Japan, Australia and South America.
• Detailed Description: Data of this trial ("VIEW 2") was pooled with data of a sister trial ("VIEW 1", NCT00509795), and an integrated analyses of the combined data was performed.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Macular Degeneration

Intervention

• Drug: Ranibizumab
  Participants received a 0.5 mg dose of Ranibizumab via intravitreal (IVT) injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.
• Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)
  Participants received a 2.0 mg dose of Aflibercept Injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.
• Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)
  Participants received a 0.5 mg dose of Aflibercept Injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.
• Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)
  Participants received a 2.0 mg dose of Aflibercept Injection administered every 8 weeks (including one additional 2,0 mg dose at Week 4) for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.

Study Arms

• Active Comparator: Ranibizumab 0.5mg Q4
  Participants received a 0.5 mg dose of Ranibizumab via intravitreal (IVT) injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.
  Intervention: Drug: Ranibizumab
• Experimental: Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q4
  Participants received a 2.0 mg dose of Aflibercept Injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.
  Intervention: Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)
• Experimental: Aflibercept Injection (EYLEA, VEGF Trap-Eye) 0.5mg Q4
  Participants received a 0.5 mg dose of Aflibercept Injection administered every 4 weeks for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.
  Intervention: Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)
• Experimental: Aflibercept Injection (EYLEA, VEGF Trap-Eye) 2mg Q8
  Participants received a 2.0 mg dose of Aflibercept Injection administered every 8 weeks (including one additional 2,0 mg dose at Week 4) for the first year. Thereafter a dose may be administered as frequently as every 4 weeks, but no less frequently than every 12 weeks.
  Intervention: Biological: Aflibercept Injection (EYLEA, VEGF Trap-Eye, BAY86-5321)

Publications *

• Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Simader C, Schmidt-Erfurth U; VIEW 1 and VIEW 2 Study Groups. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012 Dec;119(12):2537-48. doi: 10.1016/j.ophtha.2012.09.006. Epub 2012 Oct 17. Erratum in: Ophthalmology. 2013 Jan;120(1):209-10.
• Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, Brown DM, Chong V, Nguyen QD, Ho AC, Ogura Y, Simader C, Jaffe GJ, Slakter JS, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Sowade O, Zeitz O, Norenberg C, Sandbrink R, Heier JS. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology. 2014 Jan;121(1):193-201. doi: 10.1016/j.ophtha.2013.08.011. Epub 2013 Sep 29.
• Yuzawa M, Fujita K, Wittrup-Jensen KU, Norenberg C, Zeitz O, Adachi K, Wang EC, Heier J, Kaiser P, Chong V, Korobelnik JF. Improvement in vision-related function with intravitreal aflibercept: data from phase 3 studies in wet age-related macular degeneration. Ophthalmology. 2015 Mar;122(3):571-8. doi: 10.1016/j.ophtha.2014.09.024. Epub 2014 Nov 6.
• Ogura Y, Terasaki H, Gomi F, Yuzawa M, Iida T, Honda M, Nishijo K, Sowade O, Komori T, Schmidt-Erfurth U, Simader C, Chong V; VIEW 2 Investigators. Efficacy and safety of intravitreal aflibercept injection in wet age-related macular degeneration: outcomes in the Japanese subgroup of the VIEW 2 study. Br J Ophthalmol. 2015 Jan;99(1):92-7. doi: 10.1136/bjophthalmol-2014-305076. Epub 2014 Aug 8.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 30, 2010): 1240
• Original Estimated Enrollment (submitted: March 17, 2008): 1200
• Actual Study Completion Date: August 2011
• Actual Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Signed informed consent.
• Men and women >/=50 years of age.
• Active primary or recurrent subfoveal CNV lesions secondary to AMD, including juxtafoveal lesions that affect the fovea as evidenced by Fluorescein angiography (FA) in the study eye.
• ETDRS Best-Corrected Visual Acuity letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye at 4 meters.
• Willing, committed, and able to return for ALL clinic visits and complete all study-related procedures.
• Able to read, (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member) understand and willing to sign the informed consent form.

Exclusion Criteria:

• Any prior ocular (in the study eye) or systemic treatment or surgery for neovascular AMD, except dietary supplements or vitamins.
• Any prior or concomitant therapy with another investigational agent to treat neovascular AMD in the study eye.
• Any prior treatment with anti-VEGF agents in the study eye.
• Total lesion size >12 disc areas (30.5 mm, including blood, scars and neovascularization) as assessed by FA in the study eye.
• Subretinal hemorrhages that is either 50% or more of the total lesion area, or if the blood is under the fovea and is 1 or more disc areas in size in the study eye (if the blood is under the fovea, then the fovea must be surrounded by 270 degrees by visible CNV).
• Scar or fibrosis making up >50% of the total lesion in the study eye.
• Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.
• Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.
• History of any vitreous hemorrhage within 4 weeks prior to Visit 1 in the study eye.
• Presence of other causes of CNV in the study eye.
• Prior vitrectomy in the study eye.
• History of retinal detachment or treatment or surgery for retinal detachment in the study eye.
• Any history of macular hole of stage 2 and above in the study eye.
• Any intraocular or periocular surgery within 3 months of Day 1 on the study eye, except lid surgery, which may not have taken place within 1 month of Day 1, as long as it is unlikely to interfere with the injection.
• History or clinical evidence of diabetic retinopathy, diabetic macular edema or any retinal vascular disease other than AMD in either eye.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Colombia, Czech Republic, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Latvia, Mexico, Netherlands, Poland, Portugal, Singapore, Slovakia, Spain, Sweden, Switzerland, United Kingdom

Administrative Information

• NCT Number: NCT00637377
• Other Study ID Numbers: 91689; 2007-000583-25 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Bayer
• Study Sponsor: Bayer
• Collaborators: Regeneron Pharmaceuticals

Investigators

• Study Director: Bayer Study Director; Bayer

• PRS Account: Bayer
• Verification Date: November 2014