Age-Related Maculopathy, Choroidal Neovascularization
Conditions
Brief summary
The study will evaluate the safety and efficacy of the intravitreal implant of dexamethasone with Anti-VEGF treatment vs. Anti-VEGF alone (with sham dexamethasone injection) in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration.
Interventions
DRUGdexamethasone
Intravitreal injection of dexamethasone 700 µg at Day 1.
BIOLOGICALranibizumab
Ranibizumab 500 µg at day -30 and Day 7-14.
OTHERsham
Sham needle-less injection administered in the study eye at Day 1.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 50 years of age or older with subfoveal choroidal neovascularization (CNV) (classic and/or occult) secondary to AMD * Visual Acuity between 20/40 and 20/400 in the study eye
Exclusion criteria
* Any intraocular surgery within 3 months * Glaucoma * Cataract * High eye pressure * Uncontrolled systemic disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Injection Free Interval | Week 1 to Week 25 | The injection free interval was defined as the number of days between receiving the second ranibizumab injection (day 7 to 14) to the investigator's determination of eligibility to receive a third ranibizumab injection in the study eye. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Best Corrected Visual Acuity (BCVA) at Week 25 | Baseline, Week 25 | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. |
| Change From Baseline in the Mean Central Retinal Subfield Thickness at Week 25 as Assessed by Optical Coherence Tomography (OCT) in the Study Eye | Baseline, Week 25 | Optical Coherence Tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina, was performed in the study eye after pupil dilation at baseline and Month 25. |
| Change From Screening in the Area of Leakage From Choroidal Neovascularization (CNV) at Week 25 as Assessed by Fluorescein Angiography in the Study Eye | Screening (-Week 28), Week 25 | Fluorescein angiography (FA) is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. FA was performed on the study eye after dilation at Screening and Week 25. |
Countries
Australia, France, Israel, Italy, New Zealand, Portugal, South Korea, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dexamethasone and Ranibizumab Intravitreal injection of dexamethasone 700 µg at Day 1; ranibizumab 500 µg at Day -30 and Day 7-14. | 123 |
| Sham and Ranibizumab Sham injection at Day 1; ranibizumab 500 µg at day -30 and Day 7-14. | 120 |
| Total | 243 |
Baseline characteristics
| Characteristic | Dexamethasone and Ranibizumab | Sham and Ranibizumab | Total |
|---|---|---|---|
| Age, Continuous | 76.1 Years STANDARD_DEVIATION 8.83 | 76.2 Years STANDARD_DEVIATION 8.5 | 76.1 Years STANDARD_DEVIATION 8.65 |
| Sex: Female, Male Female | 76 Participants | 69 Participants | 145 Participants |
| Sex: Female, Male Male | 47 Participants | 51 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 86 / 121 | 59 / 118 |
| serious Total, serious adverse events | 9 / 121 | 14 / 118 |
Outcome results
Primary
Injection Free Interval
The injection free interval was defined as the number of days between receiving the second ranibizumab injection (day 7 to 14) to the investigator's determination of eligibility to receive a third ranibizumab injection in the study eye.
Time frame: Week 1 to Week 25
Population: Intent-to-treat population consisted of all randomized patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dexamethasone and Ranibizumab | Injection Free Interval | 34 Days |
| Sham and Ranibizumab | Injection Free Interval | 29 Days |
Secondary
Change From Baseline in the Best Corrected Visual Acuity (BCVA) at Week 25
BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Time frame: Baseline, Week 25
Population: Participants from the Intent-to-treat population (all randomized patients) with data available at Baseline and Week 25 for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexamethasone and Ranibizumab | Change From Baseline in the Best Corrected Visual Acuity (BCVA) at Week 25 | Baseline | 55.5 Letters | Standard Deviation 15.27 |
| Dexamethasone and Ranibizumab | Change From Baseline in the Best Corrected Visual Acuity (BCVA) at Week 25 | Change from baseline at week 25 | 2.0 Letters | Standard Deviation 8.61 |
| Sham and Ranibizumab | Change From Baseline in the Best Corrected Visual Acuity (BCVA) at Week 25 | Baseline | 58.1 Letters | Standard Deviation 12.64 |
| Sham and Ranibizumab | Change From Baseline in the Best Corrected Visual Acuity (BCVA) at Week 25 | Change from baseline at week 25 | 2.4 Letters | Standard Deviation 9.14 |
Secondary
Change From Baseline in the Mean Central Retinal Subfield Thickness at Week 25 as Assessed by Optical Coherence Tomography (OCT) in the Study Eye
Optical Coherence Tomography (OCT), a laser based non-invasive diagnostic system providing high-resolution imaging sections of the retina, was performed in the study eye after pupil dilation at baseline and Month 25.
Time frame: Baseline, Week 25
Population: Participants from the Intent-to-treat population (all randomized patients) with data available at Baseline and Week 25 for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexamethasone and Ranibizumab | Change From Baseline in the Mean Central Retinal Subfield Thickness at Week 25 as Assessed by Optical Coherence Tomography (OCT) in the Study Eye | Baseline | 260.28 Microns | Standard Deviation 123.625 |
| Dexamethasone and Ranibizumab | Change From Baseline in the Mean Central Retinal Subfield Thickness at Week 25 as Assessed by Optical Coherence Tomography (OCT) in the Study Eye | Change from baseline at week 25 (n=105, 111) | -7.12 Microns | Standard Deviation 77.898 |
| Sham and Ranibizumab | Change From Baseline in the Mean Central Retinal Subfield Thickness at Week 25 as Assessed by Optical Coherence Tomography (OCT) in the Study Eye | Baseline | 272.45 Microns | Standard Deviation 130.829 |
| Sham and Ranibizumab | Change From Baseline in the Mean Central Retinal Subfield Thickness at Week 25 as Assessed by Optical Coherence Tomography (OCT) in the Study Eye | Change from baseline at week 25 (n=105, 111) | -13.00 Microns | Standard Deviation 97.651 |
Secondary
Change From Screening in the Area of Leakage From Choroidal Neovascularization (CNV) at Week 25 as Assessed by Fluorescein Angiography in the Study Eye
Fluorescein angiography (FA) is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. FA was performed on the study eye after dilation at Screening and Week 25.
Time frame: Screening (-Week 28), Week 25
Population: Participants from the intent-to-treat population (all randomized participants) with data available at Screening and Week 25 for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dexamethasone and Ranibizumab | Change From Screening in the Area of Leakage From Choroidal Neovascularization (CNV) at Week 25 as Assessed by Fluorescein Angiography in the Study Eye | Screening | 8.44 Millimeters square (MM^2) | Standard Deviation 6.863 |
| Dexamethasone and Ranibizumab | Change From Screening in the Area of Leakage From Choroidal Neovascularization (CNV) at Week 25 as Assessed by Fluorescein Angiography in the Study Eye | Change from Screening at Week 25 (n= 95,99) | -2.32 Millimeters square (MM^2) | Standard Deviation 4.927 |
| Sham and Ranibizumab | Change From Screening in the Area of Leakage From Choroidal Neovascularization (CNV) at Week 25 as Assessed by Fluorescein Angiography in the Study Eye | Screening | 8.12 Millimeters square (MM^2) | Standard Deviation 6.359 |
| Sham and Ranibizumab | Change From Screening in the Area of Leakage From Choroidal Neovascularization (CNV) at Week 25 as Assessed by Fluorescein Angiography in the Study Eye | Change from Screening at Week 25 (n= 95,99) | -1.73 Millimeters square (MM^2) | Standard Deviation 5.465 |