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

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by:
Bayer
ClinicalTrials.gov Identifier:
NCT01249664
First received: November 26, 2010
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Myopia, Pathological
Biological: VEGF Trap-Eye (BAY86-5321)
Procedure: No Drug
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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) [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants Who Gained at Least 15 Letters in BCVA as Measured by ETDRS at Week 24 Using the LOCF Approach [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by ETDRS From Baseline to Week 24 - Observed Cases [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Gained at Least 10 Letters in BCVA at Week 24 - LOCF [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Gained at Least 5 Letters in BCVA at Week 24 - LOCF [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Gained at Least 15 Letters in BCVA at Week 48 - LOCF [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Gained at Least 10 Letters in BCVA at Week 48 - LOCF [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Gained at Least 5 Letters in BCVA at Week 48 - LOCF [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Lost at Least 15 Letters in BCVA at Week 24 - LOCF [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Lost at Least 10 Letters in BCVA at Week 24 - LOCF [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Lost at Least 5 Letters in BCVA at Week 24 - LOCF [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Lost at Least 15 Letters in BCVA at Week 48 - LOCF [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Lost at Least 10 Letters in BCVA at Week 48 - LOCF [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Lost at Least 5 Letters in BCVA at Week 48 - LOCF [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    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.

  • Mean Change in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) From Baseline to Week 24 - LOCF [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    A negative number indicates improvement (reduced thickness).

  • Mean Change in Central Retinal Thickness (CRT) as Assessed by Optical Coherence Tomography (OCT) From Baseline to Week 48 - LOCF [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    A negative number indicates improvement (reduced thickness).

  • Mean Change in Choroidal Neovascularization (CNV) Lesion Size as Assessed by Fluorescein Angiography (FA) From Baseline to Week 24 - LOCF [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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

  • Mean Change in Choroidal Neovascularization (CNV) Lesion Size as Assessed by Fluorescein Angiography (FA) From Baseline to Week 48 - LOCF [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    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

  • Mean Change in European Five-dimensional Health Scale (EQ-5D) Score From Baseline to Week 24 - LOCF [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    EQ-5D is a quality of life questionnaire based on a scale from -0.594 (worst) to 1.00 (best).

  • Mean Change in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score From Baseline to Week 24 - LOCF [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Who Were Withdrawn From Study Drug During the First 24 Weeks [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
  • Mean Change in Area of Leakage From Baseline at Week 24 - LOCF [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    A negative change from baseline indicates improvement, ie, less leakage.


Enrollment: 122
Study Start Date: December 2010
Study Completion Date: August 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Biological: VEGF Trap-Eye (BAY86-5321)
1 intravitreal injection of the experimental drug, followed by monthly re-injections if needed
Sham Comparator: Arm 2 Procedure: No Drug
Sham procedure NOT involving injection of any substance; patient´s eye is anesthetized and a syringe without needle gently pressed on the cornea

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01249664

Locations
Hong Kong
Kowloon, Hong Kong
Japan
Nagoya, Aichi, Japan, 466-8560
Nagoya, Aichi, Japan, 467-8602
Urayasu, Chiba, Japan, 279-0021
Matsuyama, Ehime, Japan, 790-8524
Sendai, Miyagi, Japan, 984-8560
Suita, Osaka, Japan, 565-0871
Otsu, Shiga, Japan, 520-2192
Bunkyo-ku, Tokyo, Japan, 113-8519
Chiyoda-ku, Tokyo, Japan, 101-8309
Shinjuku-ku, Tokyo, Japan, 160-8582
Fukuoka, Japan, 812-8582
Fukushima, Japan, 960-1295
Kyoto, Japan, 606-8507
Osaka, Japan, 545-8586
Osaka, Japan, 558-8558
Korea, Republic of
Seoul, Korea, Republic of, 137 701
Singapore
Singapore, Singapore, 168751
Taiwan
Taipei, Taiwan, 11217
Taoyuan, Taiwan, 333
Sponsors and Collaborators
Bayer
Regeneron Pharmaceuticals
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Therapeutic Area Head, Bayer Healthcare AG
ClinicalTrials.gov Identifier: NCT01249664     History of Changes
Other Study ID Numbers: 15170
Study First Received: November 26, 2010
Results First Received: February 16, 2014
Last Updated: April 17, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Singapore: Clinical Trials & Epidemiology Research Unit (CTERU)
Taiwan: Center for Drug Evaluation
Hong Kong: Department of Health

Keywords provided by Bayer:
sham-controlled
pathologic myopia
mCNV
choroidal neovascularization
intravitreal injection
vision loss
macular damage

Additional relevant MeSH terms:
Choroidal Neovascularization
Myopia
Neovascularization, Pathologic
Myopia, Degenerative
Choroid Diseases
Uveal Diseases
Eye Diseases
Metaplasia
Pathologic Processes
Refractive Errors

ClinicalTrials.gov processed this record on September 16, 2014