Macular Degeneration
Conditions
Brief summary
This is a safety and efficacy study of abicipar pegol in participants with neovascular age-related macular degeneration.
Interventions
DRUGAbicipar Pegol
Abicipar pegol intravitreal injection.
DRUGRanibizumab
Ranibizumab intravitreal injection.
OTHERSham Procedure
Sham injection.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of age-related macular degeneration in at least 1 eye * Best corrected visual acuity of 20/40 to 20/320 in the study eye * Best corrected visual acuity of 20/200 or better in the non-study eye
Exclusion criteria
* History of vitrectomy, macular surgery, or glaucoma surgery in the study eye * Cataract or refractive surgery in the study eye within the last 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Stable Vision at Week 52 | Baseline to Week 52 | Stable vision was defined as a loss of fewer than 15 letters in BCVA compared to baseline. BCVA was measured using an eye chart and reported as the number of letters read correctly using the Early Treatment of Diabetic Retinopathy Study (ETDRS) Scale (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. The percentage of participants with a BCVA loss of fewer than 15 letters are reported. The study eye is defined as the eye that meets the entry criteria. If both eyes met the entry criteria, the eye with the worse BCVA at baseline (Day 1) was selected as the study eye. If both eyes had same BCVA values at baseline (Day 1), then the participant had to select their non-dominant eye for treatment, or else the right eye was selected as the study eye. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in BCVA in the Study Eye at Week 52 | Baseline to Week 52 | BCVA was measured using an eye chart and was reported as the number of letters read correctly using the ETDRS Scale (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. The study eye is defined as the eye that meets the entry criteria. If both eyes met the entry criteria, the eye with the worse BCVA at baseline (Day 1) was selected as the study eye. If both eyes had same BCVA values at baseline (Day 1), then the participant had to select their nondominant eye for treatment, or else the right eye was selected as the study eye. Mixed model for repeated measures (MMRM) analysis was used. |
| Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 52 | Baseline to Week 52 | CRT was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from Baseline indicated improvement. The study eye is defined as the eye that meets the entry criteria. If both eyes met the entry criteria, the eye with the worse BCVA at baseline (Day 1) was selected as the study eye. If both eyes had same BCVA values at baseline (Day 1), then the participant had to select their non-dominant eye for treatment, or else the right eye was selected as the study eye. MMRM analysis was used. |
| Percentage of Participants With a Gain of 15 or More ETDRS Letters in BCVA From Baseline in Study Eye at Week 52 | Baseline to Week 52 | BCVA was measured using an eye chart and reported as the number of letters read correctly using the ETDRS Scale (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. The study eye is defined as the eye that meets the entry criteria. If both eyes met the entry criteria, the eye with the worse BCVA at baseline (Day 1) was selected as the study eye. If both eyes had same BCVA values at baseline (Day 1), then the participant had to select their non-dominant eye for treatment, or else the right eye was selected as the study eye. |
| Mean Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Composite Score in Study Eye at Week 52 | Baseline to Week 52 | NEI-VFQ-25 consists of 25 vision-targeted questions that represent 11 vision-related quality of life subscales and one general health item. Responses of individual participants were recorded as scores that ranged between 0 (worst) to 100 (best vision related function) with higher scale indicating better vision related function. The overall composite score is then calculated by averaging over all 11 vision-targeted subscale scores, excluding the general health score. Overall composite score was calculated based on mean of non-missing subscales. Study eye was defined as eye that meets entry criteria. If both eyes met all of entry criteria, eye with worse BCVA at baseline (day 1) was selected. If BCVA values for both eyes were identical then participant had to select non-dominant eye, or else right eye was selected as study eye. A positive change from baseline indicates improvement. MMRM analysis was used. |
Countries
Argentina, Austria, Chile, Colombia, Czechia, France, Germany, Hong Kong, Israel, Latvia, New Zealand, Philippines, Singapore, South Korea, Spain, Switzerland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abicipar Pegol 2 mg (2Q8) Abicipar pegol 2 mg was administered to the study eye by intravitreal injection on Day 1, Week 4, Week 8 and every 8 weeks (2Q8) thereafter through Week 96. Scheduled visits occurred every 4 weeks. To maintain masking, sham was administered to the study eye at scheduled visits where abicipar was not administered. | 314 |
| Abicipar Pegol 2 mg (2Q12) Abicipar pegol 2 mg was administered to the study eye by intravitreal injection on Day 1, Week 4, Week 12, and every 12 weeks (2Q12) thereafter through week 96. Scheduled visits occurred every 4 weeks. To maintain masking, sham was administered to the study eye at scheduled visits where abicipar was not administered. | 313 |
| Ranibizumab 0.5 mg (rQ4) Ranibizumab (Lucentis®) 0.5 mg was administered to the study eye by intravitreal injection every 4 weeks (rQ4) from Day 1 through Week 96. | 312 |
| Total | 939 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 47 | 51 | 25 |
| Overall Study | Lack of Efficacy | 3 | 8 | 3 |
| Overall Study | Lost to Follow-up | 4 | 4 | 1 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Reason not Specified | 4 | 6 | 5 |
| Overall Study | Screen Failure:Missed Exclusion Criteria | 1 | 1 | 2 |
| Overall Study | Withdrawal by Patient | 31 | 21 | 21 |
Baseline characteristics
| Characteristic | Abicipar Pegol 2 mg (2Q8) | Total | Ranibizumab 0.5 mg (rQ4) | Abicipar Pegol 2 mg (2Q12) |
|---|---|---|---|---|
| Age, Continuous | 75.5 years STANDARD_DEVIATION 8.4 | 76.5 years STANDARD_DEVIATION 8.3 | 77.1 years STANDARD_DEVIATION 8.4 | 76.9 years STANDARD_DEVIATION 8 |
| BCVA Per ITT Population | 56.4 letters STANDARD_DEVIATION 13.4 | 56.5 letters STANDARD_DEVIATION 12.9 | 56.5 letters STANDARD_DEVIATION 12.5 | 56.5 letters STANDARD_DEVIATION 12.9 |
| Best-corrected Visual Acuity (BCVA) Per Per-protocol Population | 56.7 letters STANDARD_DEVIATION 13.3 | 56.5 letters STANDARD_DEVIATION 13 | 56.5 letters STANDARD_DEVIATION 12.6 | 56.3 letters STANDARD_DEVIATION 13.1 |
| Central Retinal Thickness (CRT) | 384.7 microns STANDARD_DEVIATION 142.7 | 380.4 microns STANDARD_DEVIATION 127.8 | 378.2 microns STANDARD_DEVIATION 120.5 | 378.4 microns STANDARD_DEVIATION 119.1 |
| National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) | 78.7 score on a scale | 77.7 score on a scale | 77.1 score on a scale | 77.3 score on a scale |
| Race/Ethnicity, Customized Asian | 49 Participants | 138 Participants | 45 Participants | 44 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 4 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 12 Participants | 35 Participants | 11 Participants | 12 Participants |
| Race/Ethnicity, Customized Not Reported | 2 Participants | 22 Participants | 12 Participants | 8 Participants |
| Race/Ethnicity, Customized White | 249 Participants | 740 Participants | 243 Participants | 248 Participants |
| Sex: Female, Male Female | 162 Participants | 514 Participants | 169 Participants | 183 Participants |
| Sex: Female, Male Male | 152 Participants | 425 Participants | 143 Participants | 130 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 312 | 7 / 312 | 11 / 310 |
| other Total, other adverse events | 202 / 312 | 217 / 312 | 196 / 310 |
| serious Total, serious adverse events | 92 / 312 | 102 / 312 | 95 / 310 |
Outcome results
Primary
Percentage of Participants With Stable Vision at Week 52
Stable vision was defined as a loss of fewer than 15 letters in BCVA compared to baseline. BCVA was measured using an eye chart and reported as the number of letters read correctly using the Early Treatment of Diabetic Retinopathy Study (ETDRS) Scale (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. The percentage of participants with a BCVA loss of fewer than 15 letters are reported. The study eye is defined as the eye that meets the entry criteria. If both eyes met the entry criteria, the eye with the worse BCVA at baseline (Day 1) was selected as the study eye. If both eyes had same BCVA values at baseline (Day 1), then the participant had to select their non-dominant eye for treatment, or else the right eye was selected as the study eye.
Time frame: Baseline to Week 52
Population: The per-protocol (PP) population included all randomized and treated participants without any protocol deviations that impacted the primary efficacy variable and with treatment compliance to represent the intended regimen adequately.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abicipar Pegol 2 mg (2Q8) | Percentage of Participants With Stable Vision at Week 52 | 91.7 percentage of participants |
| Abicipar Pegol 2 mg (2Q12) | Percentage of Participants With Stable Vision at Week 52 | 91.2 percentage of participants |
| Ranibizumab 0.5 mg (rQ4) | Percentage of Participants With Stable Vision at Week 52 | 95.5 percentage of participants |
95.1% CI: [-8.2, 0.3]
95.1% CI: [-8.7, 0]
Secondary
Mean Change From Baseline in BCVA in the Study Eye at Week 52
BCVA was measured using an eye chart and was reported as the number of letters read correctly using the ETDRS Scale (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. The study eye is defined as the eye that meets the entry criteria. If both eyes met the entry criteria, the eye with the worse BCVA at baseline (Day 1) was selected as the study eye. If both eyes had same BCVA values at baseline (Day 1), then the participant had to select their nondominant eye for treatment, or else the right eye was selected as the study eye. Mixed model for repeated measures (MMRM) analysis was used.
Time frame: Baseline to Week 52
Population: The PP population included all randomized and treated participants without any protocol deviations that impacted the primary efficacy variable and with treatment compliance to represent the intended regimen adequately. Number of participants analyzed was based on observed data; missing data were not imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abicipar Pegol 2 mg (2Q8) | Mean Change From Baseline in BCVA in the Study Eye at Week 52 | 6.7 letters | Standard Deviation 12.9 |
| Abicipar Pegol 2 mg (2Q12) | Mean Change From Baseline in BCVA in the Study Eye at Week 52 | 5.6 letters | Standard Deviation 13.3 |
| Ranibizumab 0.5 mg (rQ4) | Mean Change From Baseline in BCVA in the Study Eye at Week 52 | 8.5 letters | Standard Deviation 13.6 |
95.1% CI: [-4.7, -0.1]
95.1% CI: [-6, -1.3]
Secondary
Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 52
CRT was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from Baseline indicated improvement. The study eye is defined as the eye that meets the entry criteria. If both eyes met the entry criteria, the eye with the worse BCVA at baseline (Day 1) was selected as the study eye. If both eyes had same BCVA values at baseline (Day 1), then the participant had to select their non-dominant eye for treatment, or else the right eye was selected as the study eye. MMRM analysis was used.
Time frame: Baseline to Week 52
Population: ITT population included all randomized participants. Number of participants analyzed was based on observed data; missing data were not imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abicipar Pegol 2 mg (2Q8) | Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 52 | -141.5 microns | Standard Deviation 136.4 |
| Abicipar Pegol 2 mg (2Q12) | Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 52 | -150.1 microns | Standard Deviation 127.4 |
| Ranibizumab 0.5 mg (rQ4) | Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 52 | -141.3 microns | Standard Deviation 122 |
95.1% CI: [-3.8, 20.9]
95.1% CI: [-10.1, 14.7]
Secondary
Mean Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Composite Score in Study Eye at Week 52
NEI-VFQ-25 consists of 25 vision-targeted questions that represent 11 vision-related quality of life subscales and one general health item. Responses of individual participants were recorded as scores that ranged between 0 (worst) to 100 (best vision related function) with higher scale indicating better vision related function. The overall composite score is then calculated by averaging over all 11 vision-targeted subscale scores, excluding the general health score. Overall composite score was calculated based on mean of non-missing subscales. Study eye was defined as eye that meets entry criteria. If both eyes met all of entry criteria, eye with worse BCVA at baseline (day 1) was selected. If BCVA values for both eyes were identical then participant had to select non-dominant eye, or else right eye was selected as study eye. A positive change from baseline indicates improvement. MMRM analysis was used.
Time frame: Baseline to Week 52
Population: ITT population included all randomized participants. Number of participants analyzed was based on observed data; missing data were not imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Abicipar Pegol 2 mg (2Q8) | Mean Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Composite Score in Study Eye at Week 52 | 2.7 score on a scale | Standard Error 0.7 |
| Abicipar Pegol 2 mg (2Q12) | Mean Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Composite Score in Study Eye at Week 52 | 3.7 score on a scale | Standard Error 0.7 |
| Ranibizumab 0.5 mg (rQ4) | Mean Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Composite Score in Study Eye at Week 52 | 4.6 score on a scale | Standard Error 0.7 |
95.1% CI: [-3.7, 0]
95.1% CI: [-2.7, 1]
Secondary
Percentage of Participants With a Gain of 15 or More ETDRS Letters in BCVA From Baseline in Study Eye at Week 52
BCVA was measured using an eye chart and reported as the number of letters read correctly using the ETDRS Scale (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. The study eye is defined as the eye that meets the entry criteria. If both eyes met the entry criteria, the eye with the worse BCVA at baseline (Day 1) was selected as the study eye. If both eyes had same BCVA values at baseline (Day 1), then the participant had to select their non-dominant eye for treatment, or else the right eye was selected as the study eye.
Time frame: Baseline to Week 52
Population: ITT population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abicipar Pegol 2 mg (2Q8) | Percentage of Participants With a Gain of 15 or More ETDRS Letters in BCVA From Baseline in Study Eye at Week 52 | 22.6 percentage of participants |
| Abicipar Pegol 2 mg (2Q12) | Percentage of Participants With a Gain of 15 or More ETDRS Letters in BCVA From Baseline in Study Eye at Week 52 | 19.2 percentage of participants |
| Ranibizumab 0.5 mg (rQ4) | Percentage of Participants With a Gain of 15 or More ETDRS Letters in BCVA From Baseline in Study Eye at Week 52 | 27.2 percentage of participants |
95.1% CI: [-11.5, 2.1]
95.1% CI: [-14.7, -1.5]