VEGF Trap-Eye in Choroidal Neovascularization Secondary to Pathologic Myopia (mCNV)

Study Overview
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Brief Summary
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VEGF Trap-Eye will be tested for safety and efficacy in patients with vision loss due to choroidal neovascularization secondary to pathologic myopia. This will be a placebo-controlled trial. 3 out of 4 patients will receive an injection of VEGF Trap-Eye into the affected eye (and repeated injections if required), and 1 out of 4 patients will receive a sham injection requiring no needle stick, but making the patient unaware of whether or not he received active treatment. Outcome of the two treatment groups will be compared after 24 weeks. From week 24, sham patients may receive active treatment. Total duration of the study will be 48 weeks.

Official Title
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A Phase-3, Multi-center, Randomized, Double-masked, Sham-controlled Study of the Efficacy, Safety, and Tolerability of Intravitreal VEGF Trap-Eye in Subjects With Choroidal Neovascularization Secondary to Pathologic Myopia

Conditions
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Myopia, Pathological

Intervention / Treatment
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* Biological: VEGF Trap-Eye (BAY86-5321)
* Procedure: No Drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to read (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent form or a family member) and understand the informed consent form and willing to sign the informed consent form Signed informed consent form. In Japan only, the informed consent form for a subject under the age of 20 years will require the co-signature of the subject's legally authorized representative. Men and women ≥ 18 years of age Myopia of greater than or equal to -6 D OR axial length of greater than or equal to 26.5 mm Active subfoveal or juxtafoveal (within 1 to 199 μm of the center of the fovea) CNV secondary to pathologic myopia as defined by leakage on FA Best-corrected visual acuity of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye at 4 meters Decrease in vision in the study eye is determined by the investigator, using his/her medical judgment, to be primarily the result of the current active mCNV Willing, committed, and able to return for all clinic visits and complete all study-related procedures Exclusion Criteria: Only one functional eye Ocular media of insufficient quality to obtain fundus and OCT images in the study eye Greatest linear dimension (GLD) of the lesion in the study eye is greater than 12 disc areas Recurrent mCNV in the study eye Aphakia in the study eye History or presence of CNV with an origin other than pathologic myopia in the study eye Ocular inflammation or external ocular inflammation in the study eye Concurrent disease in the study eye that would compromise BCVA or require medical or surgical intervention during the study period Any ocular disorder in the study eye that, in the opinion of the investigator, may confound interpretation of the study results Significant scarring or atrophy in the fovea that indicates substantial irreversible vision loss in the study eye History of idiopathic or autoimmune-associated uveitis in either eye Evidence at examination of infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye or current treatment for serious systemic infection Vitreomacular traction or traction retinal detachment, epiretinal membrane in either eye Any iris neovascularization and/or vitreous hemorrhage in either eye Uncontrolled glaucoma, or previous filtration surgery in either eye Prior and concomitant treatments In the study eye: Any prior or concomitant treatment with another investigational agent for mCNV Any previous panretinal photocoagulation or subfoveal thermal laser therapy Any prior treatment with photodynamic therapy Cataract surgery within 3 months prior to Day 1 Yttrium-aluminum-garnet laser capsulotomy within 2 months prior to Day 1 Any other intraocular surgery within 3 months prior to Day 1 History of vitreoretinal surgery and/or scleral buckle surgery Any prior treatment with anti-VEGF agents Previous use of intraocular or periocular corticosteroids in either eye within 3 months prior to Day 1 Previous assignment to treatment during this study Uncontrolled hypertension History of cerebrovascular disease or myocardial infarction within 6 months prior to Baseline/Day 1 History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect interpretation of the results of the study, or renders the subject at high risk from treatment complications Women of childbearing potential without contraception, women who intend to breastfeed during the study. All subjects (both men and women) of childbearing potential who are unwilling to use adequate birth control measures during the course of the study. Renal failure requiring dialysis or renal transplant Participation in an investigational study within 30 days prior to Screening/Visit 1 that involved treatment with any drug (excluding vitamins and minerals) or device Known serious allergy to the fluorescein sodium for injection in angiography or Verteporfin Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Biological: VEGF Trap-Eye (BAY86-5321)<br>* 1 intravitreal injection of the experimental drug, followed by monthly re-injections if needed<br>|
| Sham Comparator: Arm 2<br> | Procedure: No Drug<br>* Sham procedure NOT involving injection of any substance; patient´s eye is anesthetized and a syringe without needle gently pressed on the cornea<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) From Baseline to Week 24 - Last Observation Carried Forward (LOCF) | Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS at Week 24 Using the LOCF Approach | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed. | Baseline, Week 24 | 
| Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS From Baseline to Week 24 - Observed Cases | Data as observed at visit, no carrying forward from latest observation if missing data at later time points. Defined study baseline range of ETDRS Best Corrected Visual Acuity letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. | Baseline, Week 24 | 
| Percentage of Participants Who Gained at Least 10 Letters in BCVA at Week 24 - LOCF | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed. | Baseline, Week 24 | 
| Percentage of Participants Who Gained at Least 5 Letters in BCVA at Week 24 - LOCF | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed. | Baseline, Week 24 | 
| Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 48 - LOCF | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed. | Baseline, Week 48 | 
| Percentage of Participants Who Gained at Least 10 Letters in BCVA at Week 48 - LOCF | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed. | Baseline, Week 48 | 
| Percentage of Participants Who Gained at Least 5 Letters in BCVA at Week 48 - LOCF | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed. | Baseline, Week 48 | 
| Percentage of Participants Who Lost at Least 15 Letters in BCVA at Week 24 - LOCF | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed. | Baseline, Week 24 | 
| Percentage of Participants Who Lost at Least 10 Letters in BCVA at Week 24 - LOCF | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed. | Baseline, Week 24 | 
| Percentage of Participants Who Lost at Least 5 Letters in BCVA at Week 24 - LOCF | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed. | Baseline, Week 24 | 
| Percentage of Participants Who Lost at Least 15 Letters in BCVA at Week 48 - LOCF | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed. | Baseline, Week 48 | 
| Percentage of Participants Who Lost at Least 10 Letters in BCVA at Week 48 - LOCF | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed. | Baseline, Week 48 | 
| Percentage of Participants Who Lost at Least 5 Letters in BCVA at Week 48 - LOCF | Defined study baseline range of Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score of 73 to 35 letters (ETDRS equivalent of 20/40 to 20/200) in the study eye; a higher score represents better functioning. Nominator = (Number of participants who maintained vision * 100); Denominator = Number of participants analyzed. | Baseline, Week 48 | 
| Mean Change in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) From Baseline to Week 24 - LOCF | A negative number indicates improvement (reduced thickness). | Baseline, Week 24 | 
| Mean Change in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) From Baseline to Week 48 - LOCF | A negative number indicates improvement (reduced thickness). | Baseline, Week 48 | 
| Mean Change in Choroidal Neovascularization (CNV) Lesion Size as Assessed by Fluorescein Angiography (FA) From Baseline to Week 24 - LOCF | CNV area values measured in square millimeters, each disc area is equivalent to 2.54 mm^2 on the retina; lower values represent better outcomes | Baseline, Week 24 | 
| Mean Change in Choroidal Neovascularization (CNV) Lesion Size as Assessed by Fluorescein Angiography (FA) From Baseline to Week 48 - LOCF | CNV area values measured in square millimeters, each disc area is equivalent to 2.54 mm^2 on the retina; lower values represent better outcomes | Baseline, Week 48 | 
| Mean Change in European Five-dimensional Health Scale (EQ-5D) Score From Baseline to Week 24 - LOCF | EQ-5D is a quality of life questionnaire based on a scale from -0.594 (worst) to 1.00 (best). | Baseline, Week 24 | 
| Mean Change in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score From Baseline to Week 24 - LOCF | The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales which are all scored from 0-100. To reach the overall composite score, each sub-scale score is averaged in order to give each sub-scale equal weight. | Baseline, Week 24 | 
| Percentage of Participants Who Were Withdrawn From Study Drug During the First 24 Weeks |  | Baseline, Week 24 | 
| Mean Change in Area of Leakage From Baseline at Week 24 - LOCF | A negative change from baseline indicates improvement, ie, less leakage. | Baseline, Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sham-controlled, pathologic myopia, mCNV, choroidal neovascularization, intravitreal injection, vision loss, macular damage