Assessment of Safety, Tolerability and Pharmacokinetics of Intravitreal Pegcetacoplan (APL-2) for Patients With Wet AMD

Assessment of Safety, Tolerability and Pharmacokinetics of Intravitreal APL-2 Therapy for Neovascular Age-Related Macular Degeneration (AMD)

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02461771

Acronym

ASAP II

Enrollment

Registered

2015-06-03

Start date

2015-01-28

Completion date

2016-03-08

Last updated

2020-10-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neovascular Age-Related Macular Degeneration

Keywords

AMD, Wet AMD, Neovascular AMD

Brief summary

The objective of this study is to provide initial safety, tolerability and pharmacokinetics information of intravitreal administration of pegcetacoplan in order to support further development into larger Phase II studies for treatment of patients with AMD.

Interventions

DRUGPegcetacoplan

On treatment day, subjects will be administered a single 100 μL IVT injection of pegcetacoplan at the dose corresponding to their treatment assignment.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

50 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Male or Female 2. Age ≥ 50 years 3. The presence of an active choroidal neovascular lesion secondary to AMD 4. On treatment with anti-VEGF therapy (Lucentis®, Eylea® or Avastin®) 5. Must have received at least 3 anti-VEGF treatments over the 26-week period prior to screening (Screening Visit) 6. Evidence that the macular fluid has responded to anti-VEGF in the past based on OCT in the opinion of PI 7. At screening, evidence of subretinal fluid and retinal cystic changes 8. Must have received anti-VEGF treatment within 10 days prior to pegcetacoplan treatment (anti-VEGF can be administered on the same day of the screening visit after the screening procedures have been completed) 9. OCTs of sufficient quality to allow for the assessment of the central macular fluid can be obtained 10. Female subjects must be: * Women of non-child-bearing potential (WONCBP), Or * 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 11. 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 12. Willing and able to give informed consent

Exclusion criteria

1. Choroidal neovascularization associated with other ocular diseases such as pathologic myopia, ocular histoplasmosis or posterior uveitis, etc 2. Decreased vision due to retinal disease not attributable to choroidal neovascularization, such as nonexudative forms of AMD, geographic atrophy, inherited retinal dystrophy, uveitis or epiretinal membrane, a vitelliform-like lesion of the outer retina (e.g., as in pattern dystrophies or basal laminar drusen), idiopathic parafoveal telangiectasis, or central serous retinopathy 3. Additional ocular diseases that have irreversibly compromised or, during follow-up, could likely compromise the VA of the study eye including amblyopia, anterior ischemic optic neuropathy, clinically significant diabetic macular edema, severe non proliferative diabetic retinopathy, or proliferative diabetic retinopathy 4. Decreased vision due to significant media opacity such as corneal disease or cataract, or opacity precluding photography of the retina 5. Cataract surgery within three months of enrollment 6. Presence of any hemorrhage 7. History of treatment for CNV: 1. Previous PDT treatment within 30 days prior to enrollment in the study 2. Previous extrafoveal or juxtafoveal thermal laser photocoagulation within 30 days prior to enrollment in the study 8. Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization 9. Medical problems that make consistent follow-up over the treatment period unlikely (e.g. stroke, severe MI, end stage malignancy), or in general a poor medical risk because of other systemic diseases or active uncontrolled infections 10. Hypersensitivity to fluorescein

Design outcomes

Primary

Measure	Time frame	Description
Median Time to the Maximum Measured Serum Concentration (Tmax)	Predose (screening), postdose Day 3 to Day 113	The median Tmax is presented for each cohort. If the maximum value occurred at more than 1 time point, Tmax was defined as the first time point with this value.
Median Dose Normalized AUC(0-t)	Predose (screening), postdose Day 3 to Day 113	The AUC(0-t) was measured using the linear trapezoidal method when concentrations were increasing and the logarithmic trapezoidal method when concentrations were decreasing. The dose normalized AUC(0-t) was calculated for each subject by dividing the parameter by the subject's respective dose in milligrams. The median dose normalized AUC(0-t) is presented for each cohort.
Maximum Observed Serum Concentration (Cmax)	Predose (screening), postdose Day 3 to Day 113	The median Cmax is presented for each cohort.
Median Dose Normalized Cmax	Predose (screening), postdose Day 3 to Day 113	The dose normalized Cmax was calculated for each subject by dividing the parameter by the subject's respective dose in milligrams. The median dose normalized Cmax is presented for each cohort.
Number of Subjects Who Experienced Ocular and Systemic Adverse Events (AEs), Including by Severity	Day 1 to Day 113	Safety was assessed throughout the study. A TEAE was defined as any AE that started on/after the IVT injection of pegcetacoplan.
Number of Dose Limiting Toxicities (DLTs)	Day 1 to Day 15	The occurrence of any of the following AEs were considered DLTs: intraocular inflammation (vitritis or uveitis), endophthalmitis, sustained elevation of intraocular pressure ≥30 millimeters (mm) of mercury, and/or sustained loss of visual acuity ≥15 letters not attributable to the injection procedure or progression of disease.
Median Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-t])	Predose (screening), postdose Day 3 to Day 113	The AUC(0-t) was measured using the linear trapezoidal method when concentrations were increasing and the logarithmic trapezoidal method when concentrations were decreasing. The median AUC(0-t) is presented for each cohort.

Secondary

Measure	Time frame	Description
Median Change From Baseline in Central Retinal Thickness, Central Retinal Lesion Thickness and Central Subfield Thickness in the Study Eye	Day 1 to Day 113	Central retinal thickness, central retinal lesion thickness and central subfield thickness were determined using Spectral Domain Optical Coherence Tomography (SD-OCT).
Median Change From Baseline in Macular Cube Volume in the Study Eye	Day 1 to Day 113	Macular cube volume was determined using SD-OCT.
Median Change From Baseline in Visual Acuity for the Study Eye	Day 1 to Day 113	Best Corrected Visual Acuity (BCVA) letter score was determined using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. The score ranges from 0 to 100 letters, lower number indicating reduced visual acuity; a positive value of change from baseline indicates visual acuity gain and a negative value indicates visual acuity loss.

Countries

Australia, United States

Participant flow

Recruitment details

Male and female subjects aged at least 50 years with the presence of an active choroidal neovascular lesion secondary to age-related macular degeneration were recruited to this Phase 1 open-label, single-dose escalation study at 4 study centers in the United States and Australia.

Pre-assignment details

Subjects had received at least 3 anti-vascular endothelial growth factor treatments over the 26 week period prior to screening, and were enrolled into 1 of 3 cohorts to receive pegcetacoplan (previously known as APL-2). If both eyes were eligible for the study, the subject and Principal Investigator chose the eye that served as the study eye.

Participants by arm

Arm	Count
Cohort 1 4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1.	3
Cohort 2 10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1.	3
Cohort 3 20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1.	7
Total	13

Baseline characteristics

Characteristic	Cohort 1	Cohort 2	Cohort 3	Total
Age, Continuous	70 years	79 years	72 years	73 years
Race/Ethnicity, Customized Hispanic or Latino	0 Participants	1 Participants	2 Participants	3 Participants
Race/Ethnicity, Customized Non-Hispanic or Latino	3 Participants	2 Participants	5 Participants	10 Participants
Race/Ethnicity, Customized White	3 Participants	3 Participants	7 Participants	13 Participants
Sex: Female, Male Female	1 Participants	2 Participants	5 Participants	8 Participants
Sex: Female, Male Male	2 Participants	1 Participants	2 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 3	0 / 3	0 / 7
other Total, other adverse events	2 / 3	2 / 3	4 / 7
serious Total, serious adverse events	0 / 3	0 / 3	0 / 7