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
TRIPLE (Subject, 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 vision loss of fewer than 15 letters in Best-corrected Visual Acuity (BCVA) from baseline. BCVA is measured using an eye chart and is 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 percentage of participants with a BCVA loss of fewer than 15 letters are reported. Study eye was defined as the eye that meets the entry criteria. If both the eyes met all of the entry criteria, the eye with worse BCVA at baseline (Day 1) was selected. If BCVA values for both eyes were identical then participant had to select the non-dominant eye, or else right eye was selected as study eye. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) in the Study Eye at Week 52 | Baseline to Week 52 | BCVA was measured using an eye chart and is 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. Mixed-effect model for repeated measures (MMRM) analysis was used. Study eye is defined as the eye that meets the entry criteria. If both the eyes met all of the entry criteria, the eye with worse BCVA at baseline (Day 1) was selected. If BCVA values for both eyes were identical then participant had to select the non-dominant eye, or else right eye was selected as study eye. |
| 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 that provides high-resolution imaging sections of the retina. SD-OCT is performed in the study eye after pupil dilation. A negative change from Baseline indicates improvement and a positive change from baseline indicates worsening. Study eye is defined as the eye that meets the entry criteria. If both the eyes met all of the entry criteria, the eye with worse BCVA at baseline (Day 1) was selected. If BCVA values for both eyes were identical then participant had to select the non-dominant eye, or else right eye was selected as study eye. MMRM analysis was used. |
| Percentage of Participants With BCVA Gain of More Than 15 Letters From Baseline in the Study Eye at Week 52 | Baseline to Week 52 | BCVA is measured using an eye chart and is 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 gain of more than 15 letters are noted. Study eye is defined as the eye that meets the entry criteria. If both the eyes met all of the entry criteria, the eye with worse BCVA at baseline (Day 1) was selected. If BCVA values for both eyes were identical then participant had to select the non-dominant eye, or else right eye was selected as study eye. |
| Mean Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Composite Score 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. Overall composite score is then calculated by averaging over all 11 vision-targeted subscale scores, excluding general health score. Overall composite score was calculated based on mean of non-missing subscales. Study eye: 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
Australia, Brazil, Canada, Denmark, Hungary, Italy, Japan, Netherlands, Peru, Poland, Russia, South Africa, Taiwan, Turkey (Türkiye), United Kingdom, 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, and Week 8, followed by injections every 8 weeks 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. | 316 |
| Abicipar Pegol 2 mg (2Q12) Abicipar pegol 2 mg was administered to the study eye by intravitreal injection on Day 1, Week 4, and Week 12, followed by injections every 12 weeks 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. | 315 |
| Ranibizumab (rQ4) Ranibizumab (Lucentis®) was administered to the study eye by intravitreal injection every 4 weeks from Day 1 through Week 96. | 318 |
| Total | 949 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 53 | 48 | 21 |
| Overall Study | Lack of Efficacy | 6 | 12 | 3 |
| Overall Study | Lost to Follow-up | 3 | 4 | 2 |
| Overall Study | Protocol Violation | 3 | 1 | 1 |
| Overall Study | Reason not Specified | 3 | 4 | 3 |
| Overall Study | Screen Failure:Missed Exclusion Criteria | 1 | 1 | 3 |
| Overall Study | Withdrawal by Subject | 25 | 22 | 19 |
Baseline characteristics
| Characteristic | Total | Abicipar Pegol 2 mg (2Q12) | Ranibizumab (rQ4) | Abicipar Pegol 2 mg (2Q8) |
|---|---|---|---|---|
| Age, Continuous | 76.0 years STANDARD_DEVIATION 8.4 | 76.2 years STANDARD_DEVIATION 8.3 | 75.9 years STANDARD_DEVIATION 8.4 | 75.9 years STANDARD_DEVIATION 8.6 |
| BCVA for ITT Population | 56.9 letters STANDARD_DEVIATION 12.4 | 56.4 letters STANDARD_DEVIATION 12.5 | 57.1 letters STANDARD_DEVIATION 12.3 | 57.2 letters STANDARD_DEVIATION 12.3 |
| Best Corrected Visual Acuity (BCVA) for Per Protocol Population | 57.0 letters STANDARD_DEVIATION 12.3 | 56.3 letters STANDARD_DEVIATION 12.5 | 57.0 letters STANDARD_DEVIATION 12.3 | 57.8 letters STANDARD_DEVIATION 12.1 |
| Central Retinal Thickness (CRT) | 380.3 microns STANDARD_DEVIATION 124 | 378.2 microns STANDARD_DEVIATION 123.8 | 382.4 microns STANDARD_DEVIATION 130.3 | 380.3 microns STANDARD_DEVIATION 117.9 |
| National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) | 78 score on a scale | 78.3 score on a scale | 77.3 score on a scale | 78.4 score on a scale |
| Race/Ethnicity, Customized Asian | 115 Participants | 35 Participants | 41 Participants | 39 Participants |
| Race/Ethnicity, Customized Black | 9 Participants | 4 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic | 24 Participants | 8 Participants | 9 Participants | 7 Participants |
| Race/Ethnicity, Customized Not Reported | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 796 Participants | 266 Participants | 264 Participants | 266 Participants |
| Sex: Female, Male Female | 538 Participants | 174 Participants | 185 Participants | 179 Participants |
| Sex: Female, Male Male | 411 Participants | 141 Participants | 133 Participants | 137 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 11 / 313 | 6 / 314 | 7 / 315 |
| other Total, other adverse events | 168 / 313 | 166 / 314 | 166 / 315 |
| serious Total, serious adverse events | 94 / 313 | 83 / 314 | 78 / 315 |
Outcome results
Primary
Percentage of Participants With Stable Vision at Week 52
Stable vision was defined as vision loss of fewer than 15 letters in Best-corrected Visual Acuity (BCVA) from baseline. BCVA is measured using an eye chart and is 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 percentage of participants with a BCVA loss of fewer than 15 letters are reported. Study eye was defined as the eye that meets the entry criteria. If both the eyes met all of the entry criteria, the eye with worse BCVA at baseline (Day 1) was selected. If BCVA values for both eyes were identical then participant had to select the non-dominant eye, or else right eye was selected as study eye.
Time frame: Baseline to Week 52
Population: 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 | 94.8 percentage of participants |
| Abicipar Pegol 2 mg (2Q12) | Percentage of Participants With Stable Vision at Week 52 | 91.3 percentage of participants |
| Ranibizumab (rQ4) | Percentage of Participants With Stable Vision at Week 52 | 96.0 percentage of participants |
95% CI: [-5, 2.4]
95% CI: [-9, -0.5]
Secondary
Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) in the Study Eye at Week 52
BCVA was measured using an eye chart and is 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. Mixed-effect model for repeated measures (MMRM) analysis was used. Study eye is defined as the eye that meets the entry criteria. If both the eyes met all of the entry criteria, the eye with worse BCVA at baseline (Day 1) was selected. If BCVA values for both eyes were identical then participant had to select the non-dominant eye, or else right eye was selected as study eye.
Time frame: Baseline to Week 52
Population: 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 Best-corrected Visual Acuity (BCVA) in the Study Eye at Week 52 | 8.3 letters | Standard Deviation 14.3 |
| Abicipar Pegol 2 mg (2Q12) | Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) in the Study Eye at Week 52 | 7.3 letters | Standard Deviation 13.8 |
| Ranibizumab (rQ4) | Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) in the Study Eye at Week 52 | 8.3 letters | Standard Deviation 11.8 |
95.1% CI: [-2.4, 2]
95.1% CI: [-3.8, 0.6]
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 that provides high-resolution imaging sections of the retina. SD-OCT is performed in the study eye after pupil dilation. A negative change from Baseline indicates improvement and a positive change from baseline indicates worsening. Study eye is defined as the eye that meets the entry criteria. If both the eyes met all of the entry criteria, the eye with worse BCVA at baseline (Day 1) was selected. If BCVA values for both eyes were identical then participant had to select the non-dominant eye, or else right eye was selected as study eye. MMRM analysis was used.
Time frame: Baseline to Week 52
Population: Intent-to-treat (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 | -146.8 microns | Standard Deviation 118.1 |
| Abicipar Pegol 2 mg (2Q12) | Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 52 | -141.7 microns | Standard Deviation 127.1 |
| Ranibizumab (rQ4) | Mean Change From Baseline in Central Retinal Thickness (CRT) in the Study Eye at Week 52 | -147.1 microns | Standard Deviation 126.2 |
95.1% CI: [-7.1, 14]
95.1% CI: [-4.7, 16.5]
Secondary
Mean Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Composite Score 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. Overall composite score is then calculated by averaging over all 11 vision-targeted subscale scores, excluding general health score. Overall composite score was calculated based on mean of non-missing subscales. Study eye: 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 at Week 52 | 2.8 scores 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 at Week 52 | 2.4 scores on a scale | Standard Error 0.7 |
| Ranibizumab (rQ4) | Mean Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Composite Score at Week 52 | 4.4 scores on a scale | Standard Error 0.7 |
95.1% CI: [-3.5, 0.3]
95.1% CI: [-3.9, -0.1]
Secondary
Percentage of Participants With BCVA Gain of More Than 15 Letters From Baseline in the Study Eye at Week 52
BCVA is measured using an eye chart and is 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 gain of more than 15 letters are noted. Study eye is defined as the eye that meets the entry criteria. If both the eyes met all of the entry criteria, the eye with worse BCVA at baseline (Day 1) was selected. If BCVA values for both eyes were identical then participant had to select the non-dominant eye, or else right eye was selected as 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 BCVA Gain of More Than 15 Letters From Baseline in the Study Eye at Week 52 | 28.2 percentage of participants |
| Abicipar Pegol 2 mg (2Q12) | Percentage of Participants With BCVA Gain of More Than 15 Letters From Baseline in the Study Eye at Week 52 | 24.4 percentage of participants |
| Ranibizumab (rQ4) | Percentage of Participants With BCVA Gain of More Than 15 Letters From Baseline in the Study Eye at Week 52 | 26.7 percentage of participants |
95% CI: [-5.5, 8.4]
95% CI: [-9.1, 4.5]