Trial Outcomes & Findings for Pegcetacoplan (APL-2) in Neovascular AMD (NCT NCT03465709)

Last Updated: 2020-09-16

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

17 participants

Primary outcome timeframe

Day 1 up to end of study (up to 1 year).

Results posted on

2020-09-16

Participant Flow

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.

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).

Participant milestones

Participant milestones
Measure	15 mg Pegcetacoplan Intravitreal (IVT) injections of 15 milligrams (mg) pegcetacoplan once monthly for 12 months, followed by a 6-month safety follow-up period.
Overall Study STARTED	17
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	17

Reasons for withdrawal

Reasons for withdrawal
Measure	15 mg Pegcetacoplan Intravitreal (IVT) injections of 15 milligrams (mg) pegcetacoplan once monthly for 12 months, followed by a 6-month safety follow-up period.
Overall Study Study/Site Terminated by Sponsor	14
Overall Study Withdrawal by Subject	3

Baseline Characteristics

Pegcetacoplan (APL-2) in Neovascular AMD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	15 mg Pegcetacoplan n=17 Participants IVT injections of 15 mg pegcetacoplan once monthly for 12 months, followed by a 6-month safety follow-up period.
Age, Continuous	77.2 years STANDARD_DEVIATION 8.76 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized White	16 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	15 mg Pegcetacoplan n=17 Participants IVT injections of 15 mg pegcetacoplan once monthly for 12 months, followed by a 6-month safety follow-up period.
Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity Any TEAEs	15 Participants
Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity Ocular study eye TEAE	14 Participants
Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity Nonocular TEAE	7 Participants
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
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
Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity Serious TEAEs	4 Participants
Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity Maximum severity: mild	6 Participants
Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity Maximum severity: moderate	6 Participants
Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity Maximum severity: severe	3 Participants
Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity Maximum severity: life-threatening	0 Participants
Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity TEAEs leading to study drug discontinuation	1 Participants
Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity TEAEs leading to death	0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	15 mg Pegcetacoplan n=17 Participants IVT injections of 15 mg pegcetacoplan once monthly for 12 months, followed by a 6-month safety follow-up period.
Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months Day 30	12.9 micrometers Standard Deviation 39.06
Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months Day 120	31.6 micrometers Standard Deviation 68.33
Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months Day 150	34.8 micrometers Standard Deviation 90.50
Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months Day 180	48.3 micrometers Standard Deviation 92.21
Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months Day 210	18.5 micrometers Standard Deviation 66.06
Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months Day 240	34.1 micrometers Standard Deviation 66.35
Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months Day 270	49.2 micrometers Standard Deviation 58.76
Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months Day 300	22.2 micrometers Standard Deviation 73.29
Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months Day 360	-10.5 micrometers Standard Deviation 48.67
Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months Day 60	16.1 micrometers Standard Deviation 66.99
Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months Day 90	15.1 micrometers Standard Deviation 57.44
Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months Day 330	-0.7 micrometers Standard Deviation 57.17

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	15 mg Pegcetacoplan n=17 Participants IVT injections of 15 mg pegcetacoplan once monthly for 12 months, followed by a 6-month safety follow-up period.
Number of Subjects With Clinically Significant Change From Baseline in Physical Examination Findings, Vital Signs and Laboratory Parameters Physical examination findings	2 Participants
Number of Subjects With Clinically Significant Change From Baseline in Physical Examination Findings, Vital Signs and Laboratory Parameters Vital signs	0 Participants
Number of Subjects With Clinically Significant Change From Baseline in Physical Examination Findings, Vital Signs and Laboratory Parameters Laboratory parameters	0 Participants

Adverse Events

15 mg Pegcetacoplan: Ocular Study Eye

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

15 mg Pegcetacoplan: Ocular Fellow Eye

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

15 mg Pecgectacoplan: Non-ocular

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	15 mg Pegcetacoplan: Ocular Study Eye n=17 participants at risk Ocular TEAEs are summarized for the study eye for all subjects who received IVT injections of 15 mg pegcetacoplan once monthly for 12 months.	15 mg Pegcetacoplan: Ocular Fellow Eye n=17 participants at risk Ocular TEAEs are summarized for the fellow eye for all subjects who received IVT injections of 15 mg pegcetacoplan once monthly for 12 months.	15 mg Pecgectacoplan: Non-ocular n=17 participants at risk Non-ocular (systemic) TEAEs are summarized for all subjects who received IVT injections of 15 mg pegcetacoplan once monthly for 12 months.
Eye disorders Uveitis	11.8% 2/17 • Number of events 2 • Day 1 up to end of study (up to 1 year). The safety set included all subjects who received at least 1 dose of pegcetacoplan. Ocular TEAEs are presented separately for the study and fellow eyes, and non-ocular (systemic) TEAEs are also presented.	0.00% 0/17 • Day 1 up to end of study (up to 1 year). The safety set included all subjects who received at least 1 dose of pegcetacoplan. Ocular TEAEs are presented separately for the study and fellow eyes, and non-ocular (systemic) TEAEs are also presented.	0.00% 0/17 • Day 1 up to end of study (up to 1 year). The safety set included all subjects who received at least 1 dose of pegcetacoplan. Ocular TEAEs are presented separately for the study and fellow eyes, and non-ocular (systemic) TEAEs are also presented.
Eye disorders Non-infectious endophthalmitis	5.9% 1/17 • Number of events 1 • Day 1 up to end of study (up to 1 year). The safety set included all subjects who received at least 1 dose of pegcetacoplan. Ocular TEAEs are presented separately for the study and fellow eyes, and non-ocular (systemic) TEAEs are also presented.	0.00% 0/17 • Day 1 up to end of study (up to 1 year). The safety set included all subjects who received at least 1 dose of pegcetacoplan. Ocular TEAEs are presented separately for the study and fellow eyes, and non-ocular (systemic) TEAEs are also presented.	0.00% 0/17 • Day 1 up to end of study (up to 1 year). The safety set included all subjects who received at least 1 dose of pegcetacoplan. Ocular TEAEs are presented separately for the study and fellow eyes, and non-ocular (systemic) TEAEs are also presented.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/17 • Day 1 up to end of study (up to 1 year). The safety set included all subjects who received at least 1 dose of pegcetacoplan. Ocular TEAEs are presented separately for the study and fellow eyes, and non-ocular (systemic) TEAEs are also presented.	0.00% 0/17 • Day 1 up to end of study (up to 1 year). The safety set included all subjects who received at least 1 dose of pegcetacoplan. Ocular TEAEs are presented separately for the study and fellow eyes, and non-ocular (systemic) TEAEs are also presented.	5.9% 1/17 • Number of events 1 • Day 1 up to end of study (up to 1 year). The safety set included all subjects who received at least 1 dose of pegcetacoplan. Ocular TEAEs are presented separately for the study and fellow eyes, and non-ocular (systemic) TEAEs are also presented.

Other adverse events

Additional Information

Apellis Clinical Trial Information Line

Apellis Pharmaceuticals. Inc.

Phone: 1-833-284-6361

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place