Neovascular Age-related Macular Degeneration
Conditions
Brief summary
Safety Assessment of Pegcetacoplan in Patients with Neovascular AMD
Interventions
DRUGPegcetacoplan
Study Drug
Sponsors
Apellis Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age greater than or equal to 60 years. 2. Normal Luminance best corrected visual acuity (NL-BCVA) of 24 letters or better using Early Treatment Diabetic Retinopathy Study (ETDRS) charts (20/320 Snellen equivalent). 3. Clinical diagnosis of neovascular AMD with the following criteria met: 1. Eligible for an injection of an anti-VEGF injection with macular fluid present at Day -28. 2. Must have been treated with anti-VEGF in study eye for at least 6 months prior to joining the study. 3. At least 6 months of intravitreal anti-VEGF therapy at intervals not greater than 8 weeks (± 7 days) for the past 2 injections in the eye that is selected to be the study eye. 4. A clinically meaningful (50%) reduction in excess macular fluid or macular thickness in the study eye at the discretion of the investigator between Screening Day -28 and Screening Day -14 as assessed by SD-OCT. 5. Female subjects must be: 1. Women of non-child-bearing potential (WONCBP), or 2. Women of child-bearing potential (WOCBP) with a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study and refrain from breastfeeding for the duration of the study. 6. Males with female partners of child-bearing potential must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study. 7. Willing and able to give informed consent and to comply with the study procedures and assessments
Exclusion criteria
1. Presence of other causes of choroidal neovascularization (CNV) including pathologic myopia (spherical equivalent ≥ -6 diopters), central serous chorioretinopathy, ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, and multifocal choroiditis. 2. History of vitrectomy to the study eye 3. Presence of any ophthalmologic condition that reduces the clarity of the media and that, in the opinion of the Investigator, interferes with ophthalmologic examination (e.g. advanced cataract or corneal abnormalities). 4. Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization. 5. Any history of endophthalmitis. 6. Trabeculectomy or aqueous shunt or valve in the study eye. 7. Aphakia or absence of the posterior capsule. Note: previous violation of the posterior capsule is also excluded unless it occurred as a result of yttrium aluminum garnet (YAG) laser posterior capsulotomy in association with prior posterior chamber intraocular lens implantation and at least 60 days prior to baseline. 8. Any ophthalmic condition that may require surgery or medical intervention during the study period or, in the opinion of the Investigator, could compromise visual function during the study period (e.g. severe uncontrolled glaucoma, clinically significant diabetic macular edema, ischemic optic neuropathy, retinal vasculopathies). 9. Any contraindication to IVT injection including current ocular or periocular infection. 10. Current treatment for active systemic or localized infection. 11. Participation in any systemic experimental treatment or any other systemic investigational new drug within 6 weeks or 5 half-lives of the active (whichever is longer) prior to the start of study treatment. Note: clinical trials solely involving observation, over-the-counter vitamins, supplements, or diets are not exclusionary 12. Medical or psychiatric conditions that, in the opinion of the investigator, make consistent follow-up over the 24- month treatment period unlikely, or would make the subject an unsafe study candidate. 13. Any baseline laboratory value (hematology, serum chemistry or urinalysis) that in the opinion of the Investigator is clinically significant and not suitable for study participation. 14. Known hypersensitivity to fluorescein sodium for injection or hypersensitivity to pegcetacoplan or any of the excipients in pegcetacoplan solution
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity | Day 1 up to end of study (up to 1 year). | TEAEs were defined as those adverse events (AEs) that developed or worsened after the first dose of study drug, up to 30 days after the last dose. The severity of the TEAEs was classified as mild (asymptomatic/mild symptoms); moderate (minimal, local/non-invasive intervention indicated); severe (medically significant but not life-threatening); life-threatening or leading to death. The number of subjects experiencing 1 TEAE in each category is presented. A maximum of 7 injections of pegcetacoplan (per subject) and a maximum of 13 injections of anti-VEGF (per subject) were received during the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months | Day 1 up to Day 360 (12 months). | The CST was measured using SD-OCT throughout the study and the mean change from baseline at each timepoint is presented for the study eye. |
| Number of Subjects With Clinically Significant Change From Baseline in Physical Examination Findings, Vital Signs and Laboratory Parameters | Baseline (Screening or Day 1) up to end of study (up to 1 year). | Physical examinations, vital signs and laboratory parameters were monitored throughout the study and any subjects showing a clinically significant change from baseline over the study period are presented. |
Countries
United States
Participant flow
Recruitment details
Male and female subjects aged at least 60 years with a clinical diagnosis of neovascular age-related macular degeneration in the study eye were recruited to this Phase 1b/2, open-label study at 3 study centers in the United States conducted from 14 February 2018 until the last subject last visit on 05 April 2019.
Pre-assignment details
Subjects who demonstrated a reduction in excess macular fluid or macular thickness based on spectral domain optical coherence tomography (SD-OCT) comparison between Screening Visits 1 and 2, and who were eligible received a first anti-vascular endothelial growth factor (anti-VEGF) injection at Visit 2 and a second one at baseline (Day 1, Visit 3).
Participants by arm
| Arm | Count |
|---|---|
| 15 mg Pegcetacoplan IVT injections of 15 mg pegcetacoplan once monthly for 12 months, followed by a 6-month safety follow-up period. | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study/Site Terminated by Sponsor | 14 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | 15 mg Pegcetacoplan |
|---|---|
| Age, Continuous | 77.2 years STANDARD_DEVIATION 8.76 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized White | 16 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 | 0 / 17 |
| other Total, other adverse events | 13 / 17 | 3 / 17 | 6 / 17 |
| serious Total, serious adverse events | 3 / 17 | 0 / 17 | 1 / 17 |
Outcome results
Primary
Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity
TEAEs were defined as those adverse events (AEs) that developed or worsened after the first dose of study drug, up to 30 days after the last dose. The severity of the TEAEs was classified as mild (asymptomatic/mild symptoms); moderate (minimal, local/non-invasive intervention indicated); severe (medically significant but not life-threatening); life-threatening or leading to death. The number of subjects experiencing 1 TEAE in each category is presented. A maximum of 7 injections of pegcetacoplan (per subject) and a maximum of 13 injections of anti-VEGF (per subject) were received during the study.
Time frame: Day 1 up to end of study (up to 1 year).
Population: The safety set included all subjects who received at least 1 dose of pegcetacoplan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 15 mg Pegcetacoplan | Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity | Any TEAEs | 15 Participants |
| 15 mg Pegcetacoplan | Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity | Ocular study eye TEAE | 14 Participants |
| 15 mg Pegcetacoplan | Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity | Nonocular TEAE | 7 Participants |
| 15 mg Pegcetacoplan | Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity | TEAE at least possibly related to study drug | 5 Participants |
| 15 mg Pegcetacoplan | Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity | TEAE at least possibly related to injection | 8 Participants |
| 15 mg Pegcetacoplan | Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity | Serious TEAEs | 4 Participants |
| 15 mg Pegcetacoplan | Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity | TEAEs leading to study drug discontinuation | 1 Participants |
| 15 mg Pegcetacoplan | Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity | TEAEs leading to death | 0 Participants |
| 15 mg Pegcetacoplan | Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity | Maximum severity: mild | 6 Participants |
| 15 mg Pegcetacoplan | Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity | Maximum severity: moderate | 6 Participants |
| 15 mg Pegcetacoplan | Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity | Maximum severity: severe | 3 Participants |
| 15 mg Pegcetacoplan | Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity | Maximum severity: life-threatening | 0 Participants |
Secondary
Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months
The CST was measured using SD-OCT throughout the study and the mean change from baseline at each timepoint is presented for the study eye.
Time frame: Day 1 up to Day 360 (12 months).
Population: The intent-to-treat set included all subjects who received at least 1 dose of pegcetacoplan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg Pegcetacoplan | Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months | Day 30 | 12.9 micrometers | Standard Deviation 39.06 |
| 15 mg Pegcetacoplan | Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months | Day 60 | 16.1 micrometers | Standard Deviation 66.99 |
| 15 mg Pegcetacoplan | Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months | Day 90 | 15.1 micrometers | Standard Deviation 57.44 |
| 15 mg Pegcetacoplan | Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months | Day 120 | 31.6 micrometers | Standard Deviation 68.33 |
| 15 mg Pegcetacoplan | Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months | Day 150 | 34.8 micrometers | Standard Deviation 90.5 |
| 15 mg Pegcetacoplan | Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months | Day 180 | 48.3 micrometers | Standard Deviation 92.21 |
| 15 mg Pegcetacoplan | Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months | Day 210 | 18.5 micrometers | Standard Deviation 66.06 |
| 15 mg Pegcetacoplan | Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months | Day 240 | 34.1 micrometers | Standard Deviation 66.35 |
| 15 mg Pegcetacoplan | Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months | Day 270 | 49.2 micrometers | Standard Deviation 58.76 |
| 15 mg Pegcetacoplan | Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months | Day 300 | 22.2 micrometers | Standard Deviation 73.29 |
| 15 mg Pegcetacoplan | Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months | Day 330 | -0.7 micrometers | Standard Deviation 57.17 |
| 15 mg Pegcetacoplan | Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months | Day 360 | -10.5 micrometers | Standard Deviation 48.67 |
Secondary
Number of Subjects With Clinically Significant Change From Baseline in Physical Examination Findings, Vital Signs and Laboratory Parameters
Physical examinations, vital signs and laboratory parameters were monitored throughout the study and any subjects showing a clinically significant change from baseline over the study period are presented.
Time frame: Baseline (Screening or Day 1) up to end of study (up to 1 year).
Population: The safety set included all subjects who received at least 1 dose of pegcetacoplan.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 15 mg Pegcetacoplan | Number of Subjects With Clinically Significant Change From Baseline in Physical Examination Findings, Vital Signs and Laboratory Parameters | Physical examination findings | 2 Participants |
| 15 mg Pegcetacoplan | Number of Subjects With Clinically Significant Change From Baseline in Physical Examination Findings, Vital Signs and Laboratory Parameters | Vital signs | 0 Participants |
| 15 mg Pegcetacoplan | Number of Subjects With Clinically Significant Change From Baseline in Physical Examination Findings, Vital Signs and Laboratory Parameters | Laboratory parameters | 0 Participants |