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A. Study Design
· Phase II, Multi-center double-masked randomized clinical trial
B. Major Eligibility Criteria
· Age >=18 years
· Type 1 or type 2 diabetes
· Only one study eye per subject may be enrolled. The study eye must meet the following:
o Best corrected E-ETDRS visual acuity letter score ≥ 74 (i.e., 20/32 or better) within 8 days of enrollment
o On clinical exam, definite retinal thickening due to DME within 3000 μm of the center of the macula but not involving the central subfield
o Thickened non-central macular subfields on DRCR.net approved spectral domain OCT macular map
o Central subfield thickness within threshold definition for normal central subfield thickness on DRCR.net approved spectral domain OCT machine
o No focal/grid laser within the last 6 months or other treatment for DME within the last 4 months
o No anticipated need to treat DME during the course of the study, unless the eye meets the criteria for treatment (Central subfield retinal thickness increases to 310 μm or more in spectral domain OCT machine from baseline)
C. Run-in Phase
All potential study participants will be required to participate in a 30 day run-in phase. In order to enter the run-in phase, all eligibility criteria must be assessed and met. During this phase, the study participant will be required to use artificial tear drops 3 times per day.
At the end of the 30 day run-in phase (within an additional 30-day window after the 30 day target), compliance with the study regimen will be assessed, eligibility will be reconfirmed, and the participant's willingness to proceed into the randomized trial will be confirmed.
D. Treatment Groups
Study eyes of participants entering the randomized trial will be randomly assigned to receive either topical medication nepafenac 0.1% drops or placebo 3 times per day for 1 year. Randomization will be stratified by site.
Study participants will receive study drops with no treatment other than the study intervention for DME through 12 months unless criteria for treatment of DME are met. All study participants will continue randomized drops and visits in follow-up through 12 months regardless of whether other treatment for DME is received.
E. Follow-up Schedule
- Randomized subjects will return for follow-up visits every 4 months (±1 month) for one year.
- Testing required at each visit is summarized below.
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Run-in Phase
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0
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4M
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8M
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12M
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Visit Window
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30-60 Days
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±1M
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±1M
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±1M
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Articifial tear drops provided
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X |
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Randomization
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X |
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DME treatment assessment
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X |
X |
X |
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E-ETDRS best corrected visual acuity a
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X
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X
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X
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X
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X
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Spectral Domain OCT b
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X |
X
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X
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X
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X
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Fundus
Photos c
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X
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X
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Eye Exam d
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X
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X
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X
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X
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X
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Blood pressure
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X
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X
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HbA1c e
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X
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Compliance Assessment
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X
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X
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X
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X
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Notes:
Testing is only required for the study eye unless otherwise specified below.
a=Visual acuity performed on both eyes at each visit, including protocol refraction on both eyes at baseline (time 0 above) and month 12, and on the study eye only, at all other protocol visits. E-ETDRS refers to electronic ETDRS testing using the Electronic Visual Acuity Tester that has been validated against 4-meter chart ETDRS testing. Protocol refraction and visual acuity in the study eye also performed prior to initiating treatment for DME at study visit or non-study visit.
b= OCT also obtained prior to initiating non-study treatment for DME at a study or non-study visit. OCT may be obtained with Zeiss Cirrus, Heidelberg Spectralis, or Optovue RTVue OCT machines only.
c=Seven field or 4 wide-field digital stereoscopic photos; obtained at baseline (time 0), 12-month visit or prior to initiating treatment for DME at a study or non-study visit.
d= Both eyes at enrollment and baseline (time 0) visits study eye only at each follow-up visit including slip lamp exam, corneal and lens assessment, measurement of intraocular pressure, and dilated ophthalmoscopy.
e=Does not need to be repeated if HbA1c available from within the prior 3 months; if not available, can be performed within 3 weeks after randomization.
F. Sample Size
A minimum of 60 eyes per group for a minimum of 120 total eyes will be randomized. The total number of subjects randomized may exceed 120 randomized eyes with accurate retinal volume measurements.
G. Primary Efficacy Outcome
- Mean change in OCT measured retinal volume between baseline and 12 months
H. Main Safety Outcomes
- Corneal ulceration and melting
- Irritation
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