Neovascular Age-related Macular Degeneration
Conditions
Brief summary
This study will evaluate and compare two individualized ranibizumab treatment regimens in patients with neovascular (wet) AMD aiming to achieve and to maintain a maximum visual function benefit, while aiming to avoid unnecessary intravitreal injections. The results will be used to generate further recommendations on functional and anatomical monitoring of the disease and timing of treatment administration for patients with neovascular AMD. In this context, the study will investigate the utility of optical coherence tomography (OCT) to aid retreatment decisions with ranibizumab.
Detailed description
During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed.
Interventions
DRUGRanibizumab
Intravitreal injections of 0.5 mg Ranibizumab
Sponsors
Novartis Pharmaceuticals
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
* Visual impairment predominantly due to neovascular age-related macular degeneration AMD * Active, newly diagnosed, untreated CNV due to AMD * CNV involving the center of the retina * A qualifying vision score at study entry
Exclusion criteria
* Stroke or myocardial infarction less than 3 Months prior to study entry * Active injection or inflammation of either eye at the time of study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Best-corrected Visual Acuity (BCVA) (Letters) Change up to Month 12 | up to Month 12 | Visual acuity (VA) was assessed during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like VA testing charts at a testing distance of 4 meters. This outcome measure describes the difference between the Visual Acuity averaged up to Month 12 Level of VA (Letters) of the Study Eye. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gain of Equal or More Than 1, 5, 10, or 15 Letters in Visual Acuity of the Study Eye From Baseline, at Month 12 and 24 | Baseline to Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. |
| Loss of Less Than 5, 10, and 15 Letters in Visual Acuity in the Study Eye From Baseline, at Month 12 and 24 | Baseline to Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. |
| Visual Acuity of 73 Letters or More in the Study Eye at Month 12 and 24 | Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. |
| Average Visual Acuity Change From Month 3 to Month 4 Through Month 24 in the Study Eye | Month 3 to Month 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. |
| Average Visual Acuity Change From Baseline to Month 1 Through Month 12 and 24 in the Study Eye | Baseline to Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. |
| Change From Baseline in Visual Acuity (Letters) of the Study Eye up to Month 12 | up to Month 12 | Visual acuity (VA) was assessed using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like VA testing charts at a testing distance of 4 meters. This outcome measure describes the difference between the Visual Acuity averaged from Baseline to Month 12 Level of VA (Letters) of the Study Eye. |
| Dry Retina in the Study Eye on OCT at Month 12 and 24 | Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. |
| Change From Baseline in Lesion Size and Morphology Based on Fluorescein Angiography at Month 12 and 24 | Baseline to Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. |
| Treatment Patterns Over Time in Both Treatment Arms | Baseline to Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. |
| Change From Baseline in the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) Scores Over Time | Baseline to Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. |
| Frequency and Severity of Ocular and Non-ocular Adverse Events Over Time | Screening to Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. |
| Change From Baseline in Central Sub-Field Thickness (CSFT) and Central Sub-Field Volume (CSFV) of the Study Eye Over Time | Baseline to Month 12 and 24 | During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed. |
Countries
Argentina, Austria, Canada, Colombia, Czechia, Finland, France, Germany, Greece, Guatemala, Hungary, Ireland, Italy, Lithuania, Mexico, Netherlands, Panama, Portugal, Slovakia, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RBZ 0.5 mg: VA Only (Group I) RBZ 0.5 mg: Visual Acuity (VA) only (Group I) 0.5 mg intravitreal injections of ranibizumab with retreatment based on best-corrected visual acuity (BCVA) loss due to neovascular (wet) age-related macular degeneration (nAMD) | 335 |
| RBZ 0.5 mg: VA and/or OCT (Group II) RBZ 0.5 mg: VA and/or OCT (Group II) 0.5 mg intravitreal injections of ranibizumab with retreatment based on best-corrected visual acuity (BCVA)loss due to neovascular (wet) age-related macular degeneration (nAMD) and/or signs of wet AMD disease activity on optical coherence tomography (OCT). | 336 |
| Total | 671 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Admin problems due to early termination | 321 | 309 |
| Overall Study | Adverse Event | 2 | 4 |
| Overall Study | Death | 1 | 6 |
| Overall Study | Lost to Follow-up | 2 | 6 |
| Overall Study | Patient withdrew consent | 8 | 9 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol deviation | 0 | 1 |
Baseline characteristics
| Characteristic | RBZ 0.5 mg: VA Only (Group I) | RBZ 0.5 mg: VA and/or OCT (Group II) | Total |
|---|---|---|---|
| Age, Continuous | 73.9 years STANDARD_DEVIATION 7.86 | 75.3 years STANDARD_DEVIATION 7.91 | 74.6 years STANDARD_DEVIATION 7.91 |
| Sex: Female, Male Female | 213 Participants | 194 Participants | 407 Participants |
| Sex: Female, Male Male | 122 Participants | 142 Participants | 264 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 111 / 334 | 105 / 336 |
| serious Total, serious adverse events | 30 / 334 | 45 / 336 |
Outcome results
Primary
Average Best-corrected Visual Acuity (BCVA) (Letters) Change up to Month 12
Visual acuity (VA) was assessed during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like VA testing charts at a testing distance of 4 meters. This outcome measure describes the difference between the Visual Acuity averaged up to Month 12 Level of VA (Letters) of the Study Eye.
Time frame: up to Month 12
Population: Full Analysis Set (FAS) includes all randomized patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RBZ 0.5 mg: VA Only (Group I) | Average Best-corrected Visual Acuity (BCVA) (Letters) Change up to Month 12 | 0.1 Letters correctly read | Standard Deviation 6.79 |
| RBZ 0.5 mg: VA and/or OCT (Group II) | Average Best-corrected Visual Acuity (BCVA) (Letters) Change up to Month 12 | 1.0 Letters correctly read | Standard Deviation 7.25 |
Secondary
Average Visual Acuity Change From Baseline to Month 1 Through Month 12 and 24 in the Study Eye
During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed.
Time frame: Baseline to Month 12 and 24
Population: Early termination of the study, therefore the 12-month cutoff date was not reached and the related analysis was not performed
Secondary
Average Visual Acuity Change From Month 3 to Month 4 Through Month 24 in the Study Eye
During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed.
Time frame: Month 3 to Month 24
Population: Early termination of the study, therefore the 12-month cutoff date was not reached and the related analysis was not performed
Secondary
Change From Baseline in Central Sub-Field Thickness (CSFT) and Central Sub-Field Volume (CSFV) of the Study Eye Over Time
During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed.
Time frame: Baseline to Month 12 and 24
Population: Early termination of the study, therefore the 12-month cutoff date was not reached and the related analysis was not performed
Secondary
Change From Baseline in Lesion Size and Morphology Based on Fluorescein Angiography at Month 12 and 24
During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed.
Time frame: Baseline to Month 12 and 24
Population: Early termination of the study, therefore the 12-month cutoff date was not reached and the related analysis was not performed
Secondary
Change From Baseline in the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) Scores Over Time
During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed.
Time frame: Baseline to Month 12 and 24
Population: Early termination of the study, therefore the 12-month cutoff date was not reached and the related analysis was not performed
Secondary
Change From Baseline in Visual Acuity (Letters) of the Study Eye up to Month 12
Visual acuity (VA) was assessed using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like VA testing charts at a testing distance of 4 meters. This outcome measure describes the difference between the Visual Acuity averaged from Baseline to Month 12 Level of VA (Letters) of the Study Eye.
Time frame: up to Month 12
Population: Full Analysis Set (FAS) includes all randomized patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RBZ 0.5 mg: VA Only (Group I) | Change From Baseline in Visual Acuity (Letters) of the Study Eye up to Month 12 | 6.7 letters correctly read | Standard Deviation 13.48 |
| RBZ 0.5 mg: VA and/or OCT (Group II) | Change From Baseline in Visual Acuity (Letters) of the Study Eye up to Month 12 | 8.3 letters correctly read | Standard Deviation 13.53 |
Secondary
Dry Retina in the Study Eye on OCT at Month 12 and 24
During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed.
Time frame: Month 12 and 24
Population: Early termination of the study, therefore the 12-month cutoff date was not reached and the related analysis was not performed
Secondary
Frequency and Severity of Ocular and Non-ocular Adverse Events Over Time
During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed.
Time frame: Screening to Month 12 and 24
Population: Early termination of the study, therefore the 12-month cutoff date was not reached and the related analysis was not performed
Secondary
Gain of Equal or More Than 1, 5, 10, or 15 Letters in Visual Acuity of the Study Eye From Baseline, at Month 12 and 24
During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed.
Time frame: Baseline to Month 12 and 24
Population: Early termination of the study, therefore the 12-month cutoff date was not reached and the related analysis was not performed
Secondary
Loss of Less Than 5, 10, and 15 Letters in Visual Acuity in the Study Eye From Baseline, at Month 12 and 24
During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed.
Time frame: Baseline to Month 12 and 24
Population: Early termination of the study, therefore the 12-month cutoff date was not reached and the related analysis was not performed
Secondary
Treatment Patterns Over Time in Both Treatment Arms
During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed.
Time frame: Baseline to Month 12 and 24
Population: Early termination of the study, therefore the 12-month cutoff date was not reached and the related analysis was not performed
Secondary
Visual Acuity of 73 Letters or More in the Study Eye at Month 12 and 24
During the course of the study, the use of optical coherence tomography (OCT)-guided therapy became a standard of care accepted by health authorities and the ophthalmology community in the treatment of neovascular (wet) age-related macular degeneration (nAMD), Novartis decided on 08-Oct-2014 the early termination of the study. Therefore the 12-month cutoff date was not reached and the related analyses were not performed.
Time frame: Month 12 and 24
Population: Early termination of the study, therefore the 12-month cutoff date was not reached and the related analysis was not performed