Clinical trial NCT01249664: VEGF Trap-Eye in Choroidal Neovascularization Secondary to Pathologic Myopia (mCNV)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myopia, Pathological
Keywords: sham-controlled
pathologic myopia
mCNV
choroidal neovascularization
intravitreal injection
vision loss
macular damage
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2010-11-30
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS at Week 24 Using the LOCF Approach
timeFrame: Baseline, Week 24
measure: Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS From Baseline to Week 24 - Observed Cases
timeFrame: Baseline, Week 24
measure: Percentage of Participants Who Gained at Least 10 Letters in BCVA at Week 24 - LOCF
timeFrame: Baseline, Week 24
measure: Percentage of Participants Who Gained at Least 5 Letters in BCVA at Week 24 - LOCF
timeFrame: Baseline, Week 24
measure: Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 48 - LOCF
timeFrame: Baseline, Week 48
measure: Percentage of Participants Who Gained at Least 10 Letters in BCVA at Week 48 - LOCF
timeFrame: Baseline, Week 48
measure: Percentage of Participants Who Gained at Least 5 Letters in BCVA at Week 48 - LOCF
timeFrame: Baseline, Week 48
measure: Percentage of Participants Who Lost at Least 15 Letters in BCVA at Week 24 - LOCF
timeFrame: Baseline, Week 24
measure: Percentage of Participants Who Lost at Least 10 Letters in BCVA at Week 24 - LOCF
timeFrame: Baseline, Week 24
measure: Percentage of Participants Who Lost at Least 5 Letters in BCVA at Week 24 - LOCF
timeFrame: Baseline, Week 24
measure: Percentage of Participants Who Lost at Least 15 Letters in BCVA at Week 48 - LOCF
timeFrame: Baseline, Week 48
measure: Percentage of Participants Who Lost at Least 10 Letters in BCVA at Week 48 - LOCF
timeFrame: Baseline, Week 48
measure: Percentage of Participants Who Lost at Least 5 Letters in BCVA at Week 48 - LOCF
timeFrame: Baseline, Week 48
measure: Mean Change in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) From Baseline to Week 24 - LOCF
timeFrame: Baseline, Week 24
measure: Mean Change in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) From Baseline to Week 48 - LOCF
timeFrame: Baseline, Week 48
measure: Mean Change in Choroidal Neovascularization (CNV) Lesion Size as Assessed by Fluorescein Angiography (FA) From Baseline to Week 24 - LOCF
timeFrame: Baseline, Week 24
measure: Mean Change in Choroidal Neovascularization (CNV) Lesion Size as Assessed by Fluorescein Angiography (FA) From Baseline to Week 48 - LOCF
timeFrame: Baseline, Week 48
measure: Mean Change in European Five-dimensional Health Scale (EQ-5D) Score From Baseline to Week 24 - LOCF
timeFrame: Baseline, Week 24
measure: Mean Change in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score From Baseline to Week 24 - LOCF
timeFrame: Baseline, Week 24
measure: Percentage of Participants Who Were Withdrawn From Study Drug During the First 24 Weeks
timeFrame: Baseline, Week 24
measure: Mean Change in Area of Leakage From Baseline at Week 24 - LOCF
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Kowloon
country: Hong Kong
city: Nagoya
country: Japan
state: Aichi
city: Nagoya
country: Japan
state: Aichi
city: Urayasu
country: Japan
state: Chiba
city: Matsuyama
country: Japan
state: Ehime
city: Sendai
country: Japan
state: Miyagi
city: Suita
country: Japan
state: Osaka
city: Otsu
country: Japan
state: Shiga
city: Bunkyo-ku
country: Japan
state: Tokyo
city: Chiyoda-ku
country: Japan
state: Tokyo
city: Shinjuku-ku
country: Japan
state: Tokyo
city: Fukuoka
country: Japan
city: Fukushima
country: Japan
city: Kyoto
country: Japan
city: Osaka
country: Japan
city: Osaka
country: Japan
city: Seoul
country: Korea, Republic of
city: Singapore
country: Singapore
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: