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A Phase 2 Evaluation of
Anti-VEGF Therapy for
Diabetic Macular Edema:
Bevacizumab (Avastin)
Protocol
Status: Completed
"Click here to view protocol"
A.
Study Design
- Phase 2 randomized,
multi-center clinical trial
B.
Objectives
- To assess the dose and dose interval
related effects of intravitreal administered bevacizumab on central
retinal thickness and visual acuity in subjects with diabetic macular
edema (DME).
- To assess the effect on
intravitreal bevacizumab combined with macular photocoagulation in DME.
- To assess the safety of
intravitreal bevacizumab in subjects with DME.
This phase 2 study is
being conducted (1) to determine whether the conduct of a phase 3 trial has
merit and (2) to provide information needed to design a phase 3 trial. The
study is not designed to establish the efficacy of bevacizumab in the
treatment of diabetic macular edema.
C.
Major Eligibility Criteria
- Age >=18 years.
- Study eye with best corrected
E-ETDRS acuity >= 24 letter score (20/320 or better) and <= 78 letter
score (20/32 or worse).
- Fellow eye has acuity >=
19 letters (20/400 or better) and has not had anti-VEGF treatment within
the past 3 months and there is no expectation of such treatment in the
next 3 months.
D.
Treatment
The study eye will be randomly assigned to one of the following 5 groups
stratified by visual acuity:
1. Laser photocoagulation at baseline
o
If edema present at 12 weeks, can be treated with 2 intravitreal
injections of 1.25 mg bevacizumab spaced 6 weeks apart
2. 1.25 mg intravitreal injection of
bevacizumab at baseline and 6 weeks
3. 2.5 mg intravitreal injection of
bevacizumab at baseline and 6 weeks
4. 1.25 mg intravitreal injection of
bevacizumab at baseline (sham injection at 6 weeks)
1.25 mg intravitreal
injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and
intravitreal injection of 1.25 mg bevacizumab at 6 weeks.
E.
Duration of Follow-Up: 70 weeks
F.
Outcomes:
- Central subfield thickening
measured on OCT
- Visual acuity (measured with
E-ETDRS)
G.
Safety Outcomes:
1. Visual acuity decrease of 20 or
more letters at any visit within the first 3 weeks after a bevacizumab
injection.
2. Ocular inflammation
3. Endophthalmitis at any time
(defined as any patient treated for infectious endophthalmitis regardless of
whether a culture is positive).
4. Other reported adverse events:
injection-related, ocular, systemic.
H.
Schedule of Study Visits and Examination Procedures
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Study Week
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0*
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3
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6*
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9
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12
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18
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24
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41
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70
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E-ETDRS
visual acuity b
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Xa
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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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X
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X
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X
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OCT c
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Xa
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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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X
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Xd
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Xd
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Fundus
photos (7F)
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X
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Eye
Exam
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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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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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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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X
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X
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HbA1c
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X
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Notes:
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1. A medical history
will be elicited at baseline and an updated history at each visit.
Concomitant medications will be recorded at baseline and updated at each
visit. Adverse events will be recorded at each visit.
2. Testing is on both
eyes at each visit, except for OCT and photos which are only performed on
the study eye.
* injection of study
drug at baseline and 6 weeks.
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a =
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If
completed more than 8 days prior to randomization, must be repeated on day
of randomization.
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b =
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measurement
of best-corrected visual acuity includes protocol refraction at baseline
and at 9 weeks, and at other visits if there is a 10 or more letter
decrease from baseline; otherwise, refraction from most recent visit is
used. E-ETDRS refers to electronic ETDRS testing using the Electronic
Visual Acuity Tester that has been validated against 4-meter chart ETDRS
testing.
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c =
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OCT3,
software version 4 (or later).
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d =
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only if
performed as part of usual care.
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