Trial Outcomes & Findings for A Safety and Efficacy Trial of a Treat and Extend Protocol Using Ranibizumab With and Without Laser Photocoagulation for Diabetic Macular Edema (NCT NCT01934556)
NCT ID: NCT01934556
Last Updated: 2020-11-17
Results Overview
Mean change in ETDRS (Early Treatment in Diabetic Retinopathy Study) visual acuity at 24 months (week 92-week 107) from Day 0. Visual function of the study eye was assessed using the ETDRS protocol, which is a widely accepted international standard. A higher letter score represents better functioning"
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
150 participants
Primary outcome timeframe
2 Years
Results posted on
2020-11-17
Participant Flow
Unit of analysis: Units are Eyes
Participant milestones
| Measure |
Monthly
Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
|
TREX
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits and then underwent a treat and extend protocol of ranibizumab without navigated laser therapy.
|
GILA
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits and then underwent a treat and extend protocol of ranibizumab with navigated laser therapy.
|
|---|---|---|---|
|
Overall Study
STARTED
|
30 30
|
60 60
|
60 60
|
|
Overall Study
COMPLETED
|
25 25
|
44 44
|
50 50
|
|
Overall Study
NOT COMPLETED
|
5 5
|
16 16
|
10 10
|
Reasons for withdrawal
| Measure |
Monthly
Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
|
TREX
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits and then underwent a treat and extend protocol of ranibizumab without navigated laser therapy.
|
GILA
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits and then underwent a treat and extend protocol of ranibizumab with navigated laser therapy.
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
4
|
10
|
7
|
|
Overall Study
Death
|
1
|
5
|
2
|
Baseline Characteristics
A Safety and Efficacy Trial of a Treat and Extend Protocol Using Ranibizumab With and Without Laser Photocoagulation for Diabetic Macular Edema
Baseline characteristics by cohort
| Measure |
Monthly
n=30 Eyes
Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
Ranibizumab 0.3 mg intravitreal injection
|
TREX
n=60 Eyes
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
Ranibizumab 0.3 mg intravitreal injection
|
GILA
n=60 Eyes
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
|
Total
n=150 Eyes
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
58.7 Years
n=93 Participants
|
59.4 Years
n=4 Participants
|
59.9 Years
n=27 Participants
|
59.5 Years
n=483 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=93 Participants
|
32 Participants
n=4 Participants
|
24 Participants
n=27 Participants
|
72 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=93 Participants
|
28 Participants
n=4 Participants
|
36 Participants
n=27 Participants
|
78 Participants
n=483 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Black or African American
|
12 Participants
n=93 Participants
|
21 Participants
n=4 Participants
|
18 Participants
n=27 Participants
|
51 Participants
n=483 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=93 Participants
|
31 Participants
n=4 Participants
|
31 Participants
n=27 Participants
|
74 Participants
n=483 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
24 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=93 Participants
|
60 participants
n=4 Participants
|
60 participants
n=27 Participants
|
150 participants
n=483 Participants
|
|
Body-Mass Index
|
32.2 Units of measure "kg/m^2"
n=93 Participants
|
31.9 Units of measure "kg/m^2"
n=4 Participants
|
30.9 Units of measure "kg/m^2"
n=27 Participants
|
31.6 Units of measure "kg/m^2"
n=483 Participants
|
|
Mean Duration of Diabetes
|
15 Years
n=93 Participants
|
13.5 Years
n=4 Participants
|
13.5 Years
n=27 Participants
|
14 Years
n=483 Participants
|
|
Phakic Status
|
23 participants
n=93 Participants
|
48 participants
n=4 Participants
|
46 participants
n=27 Participants
|
117 participants
n=483 Participants
|
|
Mean Best Corrected Visual Acuity (ETDRS Letters)
|
67.5 units on a scale
n=93 Participants
|
65.5 units on a scale
n=4 Participants
|
67.0 units on a scale
n=27 Participants
|
66.5 units on a scale
n=483 Participants
|
|
Central Retinal Thickness (microns)
|
415 Microns
n=93 Participants
|
452 Microns
n=4 Participants
|
484 Microns
n=27 Participants
|
452 Microns
n=483 Participants
|
PRIMARY outcome
Timeframe: 2 YearsPopulation: For those lost to follow-up, last observation carried forward
Mean change in ETDRS (Early Treatment in Diabetic Retinopathy Study) visual acuity at 24 months (week 92-week 107) from Day 0. Visual function of the study eye was assessed using the ETDRS protocol, which is a widely accepted international standard. A higher letter score represents better functioning"
Outcome measures
| Measure |
Monthly
n=30 Participants
Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
Ranibizumab 0.3 mg intravitreal injection
|
TREX
n=60 Participants
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
Ranibizumab 0.3 mg intravitreal injection
|
GILA
n=60 Participants
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
|
|---|---|---|---|
|
Mean Change in Vision at 24 Months
|
72.5 units on a scale
Interval 67.25 to 81.5
|
75.0 units on a scale
Interval 69.0 to 80.0
|
75.0 units on a scale
Interval 69.8 to 82.3
|
SECONDARY outcome
Timeframe: 2 yearsNumber of Participants with Adverse Events, ocular and non-ocular, in each of the study groups
Outcome measures
| Measure |
Monthly
n=30 Participants
Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
Ranibizumab 0.3 mg intravitreal injection
|
TREX
n=60 Participants
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
Ranibizumab 0.3 mg intravitreal injection
|
GILA
n=60 Participants
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
|
|---|---|---|---|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Vitreomacular Traction
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Vitreous Hemorrhage
|
0 Participants
|
4 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Vitritis
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Worsening Retinopathy
|
1 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Acute Myocardial Infarction
|
0 Participants
|
5 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Angina Pectoris
|
0 Participants
|
0 Participants
|
5 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Arrhythmia
|
2 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Coronary Artery Disease
|
0 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Pneumonia
|
2 Participants
|
4 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Pulmonary Embolism
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Rhinorrhea
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Sleep apnea
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Orthostatic Hypotension
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Peripheral Vascular Disease
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Worsening Hypertension
|
10 Participants
|
21 Participants
|
26 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Cardiomyopathy
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Congestive Heart Failure
|
0 Participants
|
2 Participants
|
4 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Corneal Abrasion
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Corneal Edema
|
0 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Diplopia
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Dysphotopsia
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Elevated IOP
|
3 Participants
|
4 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Epiretinal Membrane
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Eye discomfort/discharge
|
6 Participants
|
9 Participants
|
15 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Eyelid Swelling
|
0 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Glaucoma Progression
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Hollenhorst Plaque
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Macular Hole
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Optic Neuropathy
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Photophobia
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Pingueculum
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Secondary Cataract
|
3 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Vitreous floaters
|
7 Participants
|
6 Participants
|
7 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Punctate Keratitis
|
2 Participants
|
3 Participants
|
6 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Retinal Hemorrhage
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Blepharitis
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Blurred Vision/Vision Loss
|
1 Participants
|
6 Participants
|
5 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Cataract Progression
|
1 Participants
|
5 Participants
|
7 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Chalazion
|
2 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Conjunctivitis
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Ocular Adverse Events : Conjunctival hemorrhage
|
0 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Pericardial Effusion
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Peripheral Edema
|
1 Participants
|
6 Participants
|
8 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Constipation
|
0 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Diverticulitis
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Diarrhea
|
2 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Elevated liver enzymes
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Nausea/emesis
|
1 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Gallstones
|
1 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Esophageal Reflux
|
2 Participants
|
4 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Hemorrhoids
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Incontinence
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Poor dentition
|
2 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Throat Irritation
|
3 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Anemia
|
1 Participants
|
4 Participants
|
7 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Hematoma
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Thrombocytopenia
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Allergy
|
5 Participants
|
9 Participants
|
5 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Appendicitis
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Epistaxis
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Fever
|
2 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Gastrointestinal infection
|
1 Participants
|
3 Participants
|
4 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Parotitis
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Skin Infection
|
6 Participants
|
18 Participants
|
20 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Respiratory Infection
|
12 Participants
|
22 Participants
|
14 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Sinusitis
|
5 Participants
|
9 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Urinary Tract Infection
|
4 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Elevated Creatinine
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Fatigue
|
3 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Graves disease
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Hyperammonemia
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Hypo/hyperglycemia
|
7 Participants
|
12 Participants
|
14 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Hyperlipidemia
|
5 Participants
|
4 Participants
|
6 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Hypo/hypercalcemia
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Hypo/hyperkalemia
|
0 Participants
|
1 Participants
|
5 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Hypothyroidism/nodule
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Hyperparathyroidism
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Hyperphosphatemia
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Hyperuricemia
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Testosterone deficiency
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Vitamin D Deficiency
|
1 Participants
|
3 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Weight Gain
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Arthritis
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Fractured Bone
|
2 Participants
|
3 Participants
|
9 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Hernia
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Musculoskeletal Pain
|
12 Participants
|
16 Participants
|
18 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Osteoporosis
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Skin burn
|
2 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Colon Cancer
|
1 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Lung Cancer
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Prostate Cancer
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Skin Cancer
|
1 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Cranial Nerve Palsy
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Cerebrovascular Accident
|
0 Participants
|
0 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Decreased Hearing
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Depression/Anxiety
|
0 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Dizziness
|
1 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Headache
|
6 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Insomnia
|
7 Participants
|
7 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Neuropathy
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Paresthesia
|
2 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Syncope/Presyncope
|
1 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Seizure
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Tinnitus
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Transient Ischemic Attack
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Kidney Stone
|
1 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Renal Insufficiency
|
1 Participants
|
1 Participants
|
6 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Acute Respiratory Failure
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Cough
|
2 Participants
|
5 Participants
|
5 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Dyspnea
|
0 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Nonocular AE: Lung Nodule
|
0 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Multiple imputation model for eyes lost to follow-up prior to week 104 visit.
Total number of intravitreal injections required during the first 12 months (week 46 - week 57) and the entire 24-month (week 92 - week 107) study period.
Outcome measures
| Measure |
Monthly
n=30 Participants
Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
Ranibizumab 0.3 mg intravitreal injection
|
TREX
n=60 Participants
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
Ranibizumab 0.3 mg intravitreal injection
|
GILA
n=60 Participants
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
|
|---|---|---|---|
|
Number of Intravitreal Injections
|
25.0 Injections
Interval 24.0 to 26.0
|
19.0 Injections
Interval 13.8 to 24.0
|
17.0 Injections
Interval 12.0 to 21.3
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Multiple imputation model for eyes not reaching week 104 end-point visit.
Total number of office visits and imaging studies performed during the first 12 months (week 46 - week 57) and the entire 24-month (week 92 - week 107) study period.
Outcome measures
| Measure |
Monthly
n=30 Participants
Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
Ranibizumab 0.3 mg intravitreal injection
|
TREX
n=60 Participants
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
Ranibizumab 0.3 mg intravitreal injection
|
GILA
n=60 Participants
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
|
|---|---|---|---|
|
Number of Office Visits
|
25.0 Visits
Interval 24.0 to 26.0
|
19.0 Visits
Interval 13.8 to 24.0
|
17.0 Visits
Interval 12.0 to 21.3
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: For those not reaching week 104 end-point, last observation carried forward
Mean change in central foveal thickness per SDOCT (Spectral Domain Optical Coherence Tomography) from randomization to 12 months (week46 - week 57) and randomization to 24 months (week 92 - week 107) study period.Change at month 24 reported.
Outcome measures
| Measure |
Monthly
n=30 Participants
Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
Ranibizumab 0.3 mg intravitreal injection
|
TREX
n=60 Participants
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
Ranibizumab 0.3 mg intravitreal injection
|
GILA
n=60 Participants
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
|
|---|---|---|---|
|
Change in Retinal Thickness
|
149 Microns
Interval 75.0 to 234.0
|
151 Microns
Interval 111.0 to 179.0
|
196 Microns
Interval 85.0 to 266.0
|
SECONDARY outcome
Timeframe: 2 yearsPercentage of eyes gaining or losing 3 lines of vision or more and 1 line of vision at 24 months (week 92 - week 107) from Day 0.
Outcome measures
| Measure |
Monthly
n=30 Eyes
Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
Ranibizumab 0.3 mg intravitreal injection
|
TREX
n=60 Eyes
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
Ranibizumab 0.3 mg intravitreal injection
|
GILA
n=60 Eyes
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
|
|---|---|---|---|
|
Percentage of Eyes Gaining or Losing Vision
1-line vision gainers
|
13 Eyes
|
28 Eyes
|
32 Eyes
|
|
Percentage of Eyes Gaining or Losing Vision
1-line vision losers
|
5 Eyes
|
1 Eyes
|
3 Eyes
|
|
Percentage of Eyes Gaining or Losing Vision
3-line vision gainers
|
6 Eyes
|
12 Eyes
|
15 Eyes
|
|
Percentage of Eyes Gaining or Losing Vision
3-line vision losers
|
0 Eyes
|
0 Eyes
|
0 Eyes
|
SECONDARY outcome
Timeframe: 2 yearsThe percentage of eyes which show progression of proliferative diabetic retinopathy requiring panretinal photocoagulation and/or pars plana vitrectomy over the 24-month study period.
Outcome measures
| Measure |
Monthly
n=30 Eyes
Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
Ranibizumab 0.3 mg intravitreal injection
|
TREX
n=60 Eyes
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
Ranibizumab 0.3 mg intravitreal injection
|
GILA
n=60 Eyes
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
|
|---|---|---|---|
|
Percentage of Eyes Which Progress to Proliferative Diabetic Retinopathy
|
1 Eyes
|
2 Eyes
|
2 Eyes
|
SECONDARY outcome
Timeframe: 2 yearsThe percentage of eyes in the TREX (Treat and Extend) and GILA (Guided Laser) cohorts who are eligible to begin the extension phase prior to week 104 end-point visit.
Outcome measures
| Measure |
Monthly
n=30 Eyes
Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
Ranibizumab 0.3 mg intravitreal injection
|
TREX
n=60 Eyes
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
Ranibizumab 0.3 mg intravitreal injection
|
GILA
n=60 Eyes
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
|
|---|---|---|---|
|
Percentage of Eyes Able to Begin Extension Phase Prior to Week 104 End-point Visit.
|
0 Eyes
|
49 Eyes
|
55 Eyes
|
SECONDARY outcome
Timeframe: 2 yearsFor TREX and GILA Cohorts, the time to achieve a "Secondary or Tertiary Baseline" retinal thickness.
Outcome measures
| Measure |
Monthly
n=30 Eyes
Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
Ranibizumab 0.3 mg intravitreal injection
|
TREX
n=60 Eyes
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
Ranibizumab 0.3 mg intravitreal injection
|
GILA
n=60 Eyes
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
|
|---|---|---|---|
|
Percentage of Eyes With a Secondary or Tertiary Baseline Retinal Thickness
|
0 Eyes
|
2 Eyes
|
2 Eyes
|
Adverse Events
Monthly
Serious events: 11 serious events
Other events: 30 other events
Deaths: 1 deaths
TREX
Serious events: 30 serious events
Other events: 60 other events
Deaths: 5 deaths
GILA
Serious events: 46 serious events
Other events: 60 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Monthly
n=30 participants at risk
Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
Ranibizumab 0.3 mg intravitreal injection
|
TREX
n=60 participants at risk
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
Ranibizumab 0.3 mg intravitreal injection
|
GILA
n=60 participants at risk
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
|
|---|---|---|---|
|
Eye disorders
Vitreous Hemorrhage
|
0.00%
0/30 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
|
Cardiac disorders
Myocardial Infarction
|
0.00%
0/30 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
|
Cardiac disorders
Angina Pectoris
|
0.00%
0/30 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Cardiac disorders
Cardiac Arrhythmia
|
3.3%
1/30 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Cardiac disorders
Cardiomyopathy
|
0.00%
0/30 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
|
Cardiac disorders
Congestive Heart Failure
|
0.00%
0/30 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
|
Cardiac disorders
Coronary Artery Disease
|
0.00%
0/30 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Cardiac disorders
Pericardial Effusion
|
0.00%
0/30 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Hepatobiliary disorders
Gallstones
|
0.00%
0/30 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Blood and lymphatic system disorders
Hematoma
|
3.3%
1/30 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
0.00%
0/60 • 2 years
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/30 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Immune system disorders
Allergy
|
3.3%
1/30 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
0.00%
0/60 • 2 years
|
|
Gastrointestinal disorders
Appendicitis
|
3.3%
1/30 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
0.00%
0/60 • 2 years
|
|
Infections and infestations
Gastrointestinal Infection
|
0.00%
0/30 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Infections and infestations
Parotitis
|
0.00%
0/30 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Infections and infestations
Respiratory Infection
|
0.00%
0/30 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Infections and infestations
Skin/Soft Tissue Infection
|
3.3%
1/30 • Number of events 1 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/30 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
|
Metabolism and nutrition disorders
Elevated Creatinine
|
0.00%
0/30 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Metabolism and nutrition disorders
Hyperammonemia
|
3.3%
1/30 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
0.00%
0/60 • 2 years
|
|
Endocrine disorders
Hypo/Hyperglycemia
|
0.00%
0/30 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
3.3%
1/30 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
0.00%
0/60 • 2 years
|
|
Injury, poisoning and procedural complications
Fractured Bone
|
0.00%
0/30 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
0.00%
0/30 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon Cancer
|
0.00%
0/30 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung Cancer
|
3.3%
1/30 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer
|
0.00%
0/30 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
|
Nervous system disorders
Cranial Nerve Palsy
|
0.00%
0/30 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Nervous system disorders
Cerebrovascular Accident
|
0.00%
0/30 • 2 years
|
0.00%
0/60 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Nervous system disorders
Syncope
|
0.00%
0/30 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Nervous system disorders
Transient Ischemic Attack
|
0.00%
0/30 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Renal and urinary disorders
Urolithiasis
|
3.3%
1/30 • Number of events 1 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
|
Renal and urinary disorders
Renal Failure
|
0.00%
0/30 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
3.3%
1/30 • Number of events 1 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/30 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/30 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Vascular disorders
Orthostatic Hypotension
|
0.00%
0/30 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
|
Vascular disorders
Hypertension
|
3.3%
1/30 • Number of events 1 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
10.0%
6/60 • Number of events 6 • 2 years
|
Other adverse events
| Measure |
Monthly
n=30 participants at risk
Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
Ranibizumab 0.3 mg intravitreal injection
|
TREX
n=60 participants at risk
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
Ranibizumab 0.3 mg intravitreal injection
|
GILA
n=60 participants at risk
(60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
|
|---|---|---|---|
|
Eye disorders
Blurred Vision/Vision Loss
|
3.3%
1/30 • Number of events 1 • 2 years
|
10.0%
6/60 • Number of events 6 • 2 years
|
8.3%
5/60 • Number of events 5 • 2 years
|
|
Eye disorders
Cataract Progression
|
3.3%
1/30 • Number of events 1 • 2 years
|
8.3%
5/60 • Number of events 5 • 2 years
|
11.7%
7/60 • Number of events 7 • 2 years
|
|
Eye disorders
Chalazion
|
6.7%
2/30 • Number of events 2 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Eye disorders
Elevated Intraocular Pressure
|
10.0%
3/30 • Number of events 3 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Eye disorders
Eye Discomfort/Discharge
|
20.0%
6/30 • Number of events 6 • 2 years
|
15.0%
9/60 • Number of events 9 • 2 years
|
25.0%
15/60 • Number of events 15 • 2 years
|
|
Eye disorders
Eyelid Swelling
|
0.00%
0/30 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
0.00%
0/60 • 2 years
|
|
Eye disorders
Secondary Cataract
|
10.0%
3/30 • Number of events 3 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
|
Eye disorders
Vitreous Floaters
|
23.3%
7/30 • Number of events 7 • 2 years
|
10.0%
6/60 • Number of events 6 • 2 years
|
11.7%
7/60 • Number of events 7 • 2 years
|
|
Eye disorders
Punctate Keratitis
|
6.7%
2/30 • Number of events 2 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
10.0%
6/60 • Number of events 6 • 2 years
|
|
Eye disorders
Vitreous Hemorrhage
|
0.00%
0/30 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Cardiac disorders
Myocardial Infarction
|
0.00%
0/30 • 2 years
|
8.3%
5/60 • Number of events 5 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
|
Cardiac disorders
Angina Pectoris
|
0.00%
0/30 • 2 years
|
0.00%
0/60 • 2 years
|
8.3%
5/60 • Number of events 5 • 2 years
|
|
Cardiac disorders
Cardiac Arrhythmia
|
6.7%
2/30 • Number of events 2 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Cardiac disorders
Congestive Heart Failure
|
0.00%
0/30 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
|
Vascular disorders
Peripheral Edema
|
3.3%
1/30 • Number of events 1 • 2 years
|
10.0%
6/60 • Number of events 6 • 2 years
|
13.3%
8/60 • Number of events 8 • 2 years
|
|
Gastrointestinal disorders
Diarrhea
|
6.7%
2/30 • Number of events 2 • 2 years
|
0.00%
0/60 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Hepatobiliary disorders
Gallstones
|
3.3%
1/30 • Number of events 1 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Gastrointestinal disorders
Esophageal Reflux
|
6.7%
2/30 • Number of events 2 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
General disorders
Poor Dentition
|
6.7%
2/30 • Number of events 2 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Gastrointestinal disorders
Throat Irritation
|
10.0%
3/30 • Number of events 3 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Blood and lymphatic system disorders
Anemia
|
3.3%
1/30 • Number of events 1 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
11.7%
7/60 • Number of events 7 • 2 years
|
|
Immune system disorders
Allergy
|
16.7%
5/30 • Number of events 5 • 2 years
|
15.0%
9/60 • Number of events 9 • 2 years
|
8.3%
5/60 • Number of events 5 • 2 years
|
|
Infections and infestations
Fever
|
6.7%
2/30 • Number of events 2 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Infections and infestations
Gastrointestinal Infection
|
3.3%
1/30 • Number of events 1 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
|
Infections and infestations
Skin Infection
|
20.0%
6/30 • Number of events 6 • 2 years
|
30.0%
18/60 • Number of events 18 • 2 years
|
33.3%
20/60 • Number of events 20 • 2 years
|
|
Infections and infestations
Respiratory Infection
|
40.0%
12/30 • Number of events 12 • 2 years
|
36.7%
22/60 • Number of events 22 • 2 years
|
23.3%
14/60 • Number of events 14 • 2 years
|
|
Infections and infestations
Sinusitis
|
16.7%
5/30 • Number of events 5 • 2 years
|
15.0%
9/60 • Number of events 9 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Infections and infestations
Urinary Tract Infection
|
13.3%
4/30 • Number of events 4 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
General disorders
Fatigue
|
10.0%
3/30 • Number of events 3 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
|
Endocrine disorders
Hypo/Hyperglycemia
|
23.3%
7/30 • Number of events 7 • 2 years
|
20.0%
12/60 • Number of events 12 • 2 years
|
23.3%
14/60 • Number of events 14 • 2 years
|
|
Metabolism and nutrition disorders
Hyperlipidemia
|
16.7%
5/30 • Number of events 5 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
10.0%
6/60 • Number of events 6 • 2 years
|
|
Metabolism and nutrition disorders
Hypo/Hyperkalemia
|
0.00%
0/30 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
8.3%
5/60 • Number of events 5 • 2 years
|
|
Endocrine disorders
Testosterone Deficiency
|
6.7%
2/30 • Number of events 2 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
0.00%
0/60 • 2 years
|
|
Metabolism and nutrition disorders
Vitamin D Deficiency
|
3.3%
1/30 • Number of events 1 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
|
Injury, poisoning and procedural complications
Fractured Bone
|
6.7%
2/30 • Number of events 2 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
15.0%
9/60 • Number of events 9 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
40.0%
12/30 • Number of events 12 • 2 years
|
26.7%
16/60 • Number of events 16 • 2 years
|
30.0%
18/60 • Number of events 18 • 2 years
|
|
Skin and subcutaneous tissue disorders
Skin Burn
|
6.7%
2/30 • Number of events 2 • 2 years
|
3.3%
2/60 • Number of events 2 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon Cancer
|
3.3%
1/30 • Number of events 1 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Psychiatric disorders
Depression/Anxiety
|
0.00%
0/30 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Ear and labyrinth disorders
Dizziness
|
3.3%
1/30 • Number of events 1 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Headache
|
20.0%
6/30 • Number of events 6 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
General disorders
Insomnia
|
23.3%
7/30 • Number of events 7 • 2 years
|
11.7%
7/60 • Number of events 7 • 2 years
|
0.00%
0/60 • 2 years
|
|
Nervous system disorders
Paresthesia
|
6.7%
2/30 • Number of events 2 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
|
Renal and urinary disorders
Renal Insufficiency
|
3.3%
1/30 • Number of events 1 • 2 years
|
1.7%
1/60 • Number of events 1 • 2 years
|
10.0%
6/60 • Number of events 6 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.7%
2/30 • Number of events 2 • 2 years
|
8.3%
5/60 • Number of events 5 • 2 years
|
8.3%
5/60 • Number of events 5 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
6.7%
2/30 • Number of events 2 • 2 years
|
6.7%
4/60 • Number of events 4 • 2 years
|
5.0%
3/60 • Number of events 3 • 2 years
|
|
Vascular disorders
Hypertension
|
33.3%
10/30 • Number of events 10 • 2 years
|
35.0%
21/60 • Number of events 21 • 2 years
|
43.3%
26/60 • Number of events 26 • 2 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place