Age Related Macular Degeneration
Conditions
Keywords
Age-related macular degeneration, ranibizumab
Brief summary
The study will test if the efficacy and safety of an alternative dosing regimen is as effective as monthly injections.
Interventions
DRUGRanibizumab 0.3 mg - 3 times monthly, then quarterly
Subjects received intravitreal injections (in the study eye) of ranibizumab 0.3 mg over a duration of 12 months. They were treated monthly for 3 consecutive months and then quarterly for the remainder of the study. On those months when ranibizumab was not administered, patients received a sham injection to preserve the masking of the treatment arms.
DRUGRanibizumab 0.5 mg - 3 times monthly, then quarterly
Subjects received intravitreal injections (in the study eye) of ranibizumab 0.5 mg over a duration of 12 months. They were treated monthly for 3 consecutive months and then quarterly for the remainder of the study. On those months when ranibizumab was not administered, patients received a sham injection to preserve the masking of the treatment arms.
DRUGRanibizumab 0.3 mg monthly
Subjects received monthly intravitreal injections (in the study eye) of ranibizumab 0.5 mg over a duration of 12 months. On those months when ranibizumab was not administered, patients received a sham injection to preserve the masking of the treatment arms.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with primary or recurrent subfoveal CNV secondary to AMD, including those with predominantly classic, minimally classic or occult lesions with no classic component * Patients who have a BCVA score between 73 and 24 letters, inclusively, in the study eye using ETDRS-like grading charts (approximately 20/40 to 20/320)
Exclusion criteria
* Prior treatment in the study eye with verteporfin, external-beam radiation therapy, subfoveal focal laser photocoagulation, vitrectomy, or transpupillary thermotherapy. * History of submacular surgery or other surgical intervention for AMD in the study eye, glaucoma filtration surgery, corneal transplant surgery. * Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within one month preceding Baseline. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Best-corrected Visual Acuity of the Study Eye at Month 12 | Baseline to Month 12 | Visual acuity (VA) was assessed in both eyes at each study visit using best correction determined from protocol refraction. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at an initial testing distance of 4 meters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Total Lesion Area of the Study Eye at Month 12 | Baseline to Month 12 | Fluorescein angiography was conducted in conjunction with color fundus photography at screening and at Months 6 and 12. Investigators used digital fluorescein angiograms to determine presence or absence of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). |
| Mean Change From Baseline in Retinal Thickness at the Central Point of the Study Eye at Month 12 | Baseline to Month 12 | Optical Coherence Tomography (OCT) was performed on both eyes at screening and monthly from baseline through Month 12 prior to study drug administration. OCT images were evaluated at the central reading center (CRC) by trained graders and ophthalmologists experienced in clinical trials. |
| Mean Change From Baseline in Retinal Thickness at the Central Subfield of the Study Eye at Month 12 | Baseline to Month 12 | Optical Coherence Tomography (OCT) was performed on both eyes at screening and monthly from baseline through Month 12 prior to study drug administration. OCT images were evaluated at the central reading center (CRC) by trained graders and ophthalmologists experienced in clinical trials. |
Countries
Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ranibizumab 0.3 mg - 3 Times Monthly, Then Quarterly Subjects received intravitreal injections (in the study eye) of ranibizumab 0.3 mg over a duration of 12 months. They were treated monthly for 3 consecutive months and then quarterly for the remainder of the study. On those months when ranibizumab was not administered, patients received a sham injection to preserve the masking of the treatment arms. | 120 |
| Ranibizumab 0.5 mg - 3 Times Monthly, Then Quarterly Subjects received intravitreal injections (in the study eye) of ranibizumab 0.5 mg over a duration of 12 months. They were treated monthly for 3 consecutive months and then quarterly for the remainder of the study. On those months when ranibizumab was not administered, patients received a sham injection to preserve the masking of the treatment arms. | 118 |
| Ranibizumab 0.3 mg Monthly Subjects received monthly intravitreal injections (in the study eye) of ranibizumab 0.5 mg over a duration of 12 months. On those months when ranibizumab was not administered, patients received a sham injection to preserve the masking of the treatment arms. | 115 |
| Total | 353 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative problems | 3 | 4 | 4 |
| Overall Study | Adverse Event | 4 | 12 | 5 |
| Overall Study | Death | 0 | 2 | 1 |
| Overall Study | Lack of Efficacy | 2 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 |
| Overall Study | Protocol Violation | 5 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Ranibizumab 0.3 mg - 3 Times Monthly, Then Quarterly | Ranibizumab 0.5 mg - 3 Times Monthly, Then Quarterly | Ranibizumab 0.3 mg Monthly | Total |
|---|---|---|---|---|
| Age, Customized 50 - < 65 | 13 Participants | 12 Participants | 10 Participants | 35 Participants |
| Age, Customized 65 - < 75 | 37 Participants | 28 Participants | 45 Participants | 110 Participants |
| Age, Customized 75 - < 85 | 61 Participants | 72 Participants | 46 Participants | 179 Participants |
| Age, Customized ≥ 85 | 9 Participants | 6 Participants | 14 Participants | 29 Participants |
| Sex: Female, Male Female | 70 Participants | 73 Participants | 66 Participants | 209 Participants |
| Sex: Female, Male Male | 50 Participants | 45 Participants | 49 Participants | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 66 / 120 | 71 / 118 | 64 / 115 |
| serious Total, serious adverse events | 15 / 120 | 23 / 118 | 20 / 115 |
Outcome results
Primary
Mean Change From Baseline in Best-corrected Visual Acuity of the Study Eye at Month 12
Visual acuity (VA) was assessed in both eyes at each study visit using best correction determined from protocol refraction. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at an initial testing distance of 4 meters.
Time frame: Baseline to Month 12
Population: Per-Protocol (PP) population includes a subset of patients from the Intent to Treat (ITT) population who completed Month 12/Visit 15, had an assessment of Best Corrected Visual Acuity in the study eye at Month 12/Visit 15 and did not have any major study protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab 0.3 mg - 3 Times Monthly, Then Quarterly | Mean Change From Baseline in Best-corrected Visual Acuity of the Study Eye at Month 12 | 4.9 letters | Standard Deviation 13.13 |
| Ranibizumab 0.5 mg - 3 Times Monthly, Then Quarterly | Mean Change From Baseline in Best-corrected Visual Acuity of the Study Eye at Month 12 | 3.8 letters | Standard Deviation 13.33 |
| Ranibizumab 0.3 mg Monthly | Mean Change From Baseline in Best-corrected Visual Acuity of the Study Eye at Month 12 | 8.3 letters | Standard Deviation 11.31 |
Secondary
Mean Change From Baseline in Retinal Thickness at the Central Point of the Study Eye at Month 12
Optical Coherence Tomography (OCT) was performed on both eyes at screening and monthly from baseline through Month 12 prior to study drug administration. OCT images were evaluated at the central reading center (CRC) by trained graders and ophthalmologists experienced in clinical trials.
Time frame: Baseline to Month 12
Population: Intent to Treat (ITT) population, with use of Last Observation Carried Forward (LOCF), consisted of all patients randomized into the study. Patients were analyzed according to the treatment group to which they were randomized. Only patients with available data at baseline and Month 12 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab 0.3 mg - 3 Times Monthly, Then Quarterly | Mean Change From Baseline in Retinal Thickness at the Central Point of the Study Eye at Month 12 | -96.0 micrometers | Standard Deviation 96.82 |
| Ranibizumab 0.5 mg - 3 Times Monthly, Then Quarterly | Mean Change From Baseline in Retinal Thickness at the Central Point of the Study Eye at Month 12 | -105.6 micrometers | Standard Deviation 128.98 |
| Ranibizumab 0.3 mg Monthly | Mean Change From Baseline in Retinal Thickness at the Central Point of the Study Eye at Month 12 | -105.3 micrometers | Standard Deviation 128.55 |
Secondary
Mean Change From Baseline in Retinal Thickness at the Central Subfield of the Study Eye at Month 12
Optical Coherence Tomography (OCT) was performed on both eyes at screening and monthly from baseline through Month 12 prior to study drug administration. OCT images were evaluated at the central reading center (CRC) by trained graders and ophthalmologists experienced in clinical trials.
Time frame: Baseline to Month 12
Population: Intent to Treat (ITT) population, with use of Last Observation Carried Forward (LOCF), consisted of all patients randomized into the study. Patients were analyzed according to the treatment group to which they were randomized. Only patients with available data at baseline and Month 12 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab 0.3 mg - 3 Times Monthly, Then Quarterly | Mean Change From Baseline in Retinal Thickness at the Central Subfield of the Study Eye at Month 12 | -93.3 Micrometers | Standard Deviation 100.88 |
| Ranibizumab 0.5 mg - 3 Times Monthly, Then Quarterly | Mean Change From Baseline in Retinal Thickness at the Central Subfield of the Study Eye at Month 12 | -97.5 Micrometers | Standard Deviation 117.52 |
| Ranibizumab 0.3 mg Monthly | Mean Change From Baseline in Retinal Thickness at the Central Subfield of the Study Eye at Month 12 | -97.9 Micrometers | Standard Deviation 112.47 |
Secondary
Mean Change From Baseline in the Total Lesion Area of the Study Eye at Month 12
Fluorescein angiography was conducted in conjunction with color fundus photography at screening and at Months 6 and 12. Investigators used digital fluorescein angiograms to determine presence or absence of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).
Time frame: Baseline to Month 12
Population: The intent to treat (ITT) population, with use of Last Observation Carried Forward (LOCF), consisted of all patients randomized into the study. Patients were analyzed according to the treatment group to which they were randomized. Only patients with available data at baseline and Month 12 were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranibizumab 0.3 mg - 3 Times Monthly, Then Quarterly | Mean Change From Baseline in the Total Lesion Area of the Study Eye at Month 12 | -0.21 mm^2 | Standard Deviation 5.616 |
| Ranibizumab 0.5 mg - 3 Times Monthly, Then Quarterly | Mean Change From Baseline in the Total Lesion Area of the Study Eye at Month 12 | -1.51 mm^2 | Standard Deviation 4.802 |
| Ranibizumab 0.3 mg Monthly | Mean Change From Baseline in the Total Lesion Area of the Study Eye at Month 12 | -1.28 mm^2 | Standard Deviation 4.367 |