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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pegcetacoplan Cohort 1 | Experimental | 4 mg of pegcetacoplan 100 μL IVT injection |
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| Pegcetacoplan Cohort 2 | Experimental | 10 mg of pegcetacoplan 100 μL IVT injection |
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| Pegcetacoplan Cohort 3 | Experimental | 20 mg of pegcetacoplan 100 μL IVT injection |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pegcetacoplan | Drug | On treatment day, subjects will be administered a single 100 μL IVT injection of pegcetacoplan at the dose corresponding to their treatment assignment. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects Who Experienced Ocular and Systemic Adverse Events (AEs), Including by Severity | Safety was assessed throughout the study. A TEAE was defined as any AE that started on/after the IVT injection of pegcetacoplan. | Day 1 to Day 113 |
| Number of Dose Limiting Toxicities (DLTs) | 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. | Day 1 to Day 15 |
| Median Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-t]) | 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. | Predose (screening), postdose Day 3 to Day 113 |
| Median Dose Normalized AUC(0-t) | 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. | Predose (screening), postdose Day 3 to Day 113 |
| Maximum Observed Serum Concentration (Cmax) | The median Cmax is presented for each cohort. | Predose (screening), postdose Day 3 to Day 113 |
| Measure | Description | Time Frame |
|---|---|---|
| Median Change From Baseline in Visual Acuity for the Study Eye | 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. |
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Inclusion Criteria:
Male or Female
Age ≥ 50 years
The presence of an active choroidal neovascular lesion secondary to AMD
On treatment with anti-VEGF therapy (Lucentis®, Eylea® or Avastin®)
Must have received at least 3 anti-VEGF treatments over the 26-week period prior to screening (Screening Visit)
Evidence that the macular fluid has responded to anti-VEGF in the past based on OCT in the opinion of PI
At screening, evidence of subretinal fluid and retinal cystic changes
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)
OCTs of sufficient quality to allow for the assessment of the central macular fluid can be obtained
Female subjects must be:
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
Willing and able to give informed consent
Exclusion Criteria:
Choroidal neovascularization associated with other ocular diseases such as pathologic myopia, ocular histoplasmosis or posterior uveitis, etc
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
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
Decreased vision due to significant media opacity such as corneal disease or cataract, or opacity precluding photography of the retina
Cataract surgery within three months of enrollment
Presence of any hemorrhage
History of treatment for CNV:
Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization
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
Hypersensitivity to fluorescein
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| Name | Affiliation | Role |
|---|---|---|
| Federico Grossi, MD PhD | Apellis Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| United States, California | Beverly Hills | California | 90211 | United States | ||
| United States, Florida |
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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | 4 milligrams (mg) pegcetacoplan: Subjects received a single intravitreal (IVT) injection of pegcetacoplan (100 microliters [μL] of 40 mg per milliliter [mg/mL]) on Day 1. |
| FG001 | Cohort 2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Median Dose Normalized Cmax |
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. |
| Predose (screening), postdose Day 3 to Day 113 |
| Median Time to the Maximum Measured Serum Concentration (Tmax) | 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. | Predose (screening), postdose Day 3 to Day 113 |
| Day 1 to Day 113 |
| Median Change From Baseline in Central Retinal Thickness, Central Retinal Lesion Thickness and Central Subfield Thickness in the Study Eye | Central retinal thickness, central retinal lesion thickness and central subfield thickness were determined using Spectral Domain Optical Coherence Tomography (SD-OCT). | Day 1 to Day 113 |
| Median Change From Baseline in Macular Cube Volume in the Study Eye | Macular cube volume was determined using SD-OCT. | Day 1 to Day 113 |
| Miami |
| Florida |
| 33136 |
| United States |
| United States, New Hampshire | Portsmouth | New Hampshire | 03801 | United States |
| Australia, New South Wells | Parramatta | New South Wales | 2150 | Australia |
10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1.
| FG002 | Cohort 3 | 20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1. |
| COMPLETED | Completed acute safety observation period (up to Day 15) and follow-up visits up to Day 113. |
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| NOT COMPLETED |
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The safety set included all subjects who received any amount of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | 4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1. |
| BG001 | Cohort 2 | 10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1. |
| BG002 | Cohort 3 | 20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants | No |
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| Race/Ethnicity, Customized | Count of Participants | Participants | No |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Subjects Who Experienced Ocular and Systemic Adverse Events (AEs), Including by Severity | Safety was assessed throughout the study. A TEAE was defined as any AE that started on/after the IVT injection of pegcetacoplan. | The safety set included all subjects who received any amount of study drug. | Posted | Count of Participants | Participants | No | Day 1 to Day 113 |
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| Primary | Number of Dose Limiting Toxicities (DLTs) | 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. | The safety set included all subjects who received any amount of study drug. | Posted | Number | Number of DLTs | Day 1 to Day 15 |
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| Primary | Median Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-t]) | 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. | The pharmacokinetic (PK) set included all subjects in the safety set who had at least one postdose PK sample drawn with a measurable serum concentration of the study drug (even if the concentration was < lower limit of quantification). | Posted | Median | Full Range | micrograms*day/milliliter (μg*day/mL) | Predose (screening), postdose Day 3 to Day 113 |
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| Primary | Median Dose Normalized AUC(0-t) | 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. | The PK set included all subjects in the safety set who had at least one postdose PK sample drawn with a measurable serum concentration of the study drug (even if the concentration was < lower limit of quantification). | Posted | Median | Full Range | (μg*day/mL)/respective mg dose | Predose (screening), postdose Day 3 to Day 113 |
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| Primary | Maximum Observed Serum Concentration (Cmax) | The median Cmax is presented for each cohort. | The PK set included all subjects in the safety set who had at least one postdose PK sample drawn with a measurable serum concentration of the study drug (even if the concentration was < lower limit of quantification). | Posted | Median | Full Range | μg/mL | Predose (screening), postdose Day 3 to Day 113 |
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| Primary | Median Dose Normalized Cmax | 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. | The PK set included all subjects in the safety set who had at least one postdose PK sample drawn with a measurable serum concentration of the study drug (even if the concentration was < lower limit of quantification). | Posted | Median | Full Range | (μg/mL)/respective mg dose | Predose (screening), postdose Day 3 to Day 113 |
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| Primary | Median Time to the Maximum Measured Serum Concentration (Tmax) | 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. | The PK set included all subjects in the safety set who had at least one postdose PK sample drawn with a measurable serum concentration of the study drug (even if the concentration was < lower limit of quantification). | Posted | Median | Full Range | day | Predose (screening), postdose Day 3 to Day 113 |
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| Secondary | Median Change From Baseline in Visual Acuity for the Study Eye | 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. | The efficacy set included all subjects who received any amount of the study drug. | Posted | Median | Full Range | letters read correctly | Day 1 to Day 113 |
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| Secondary | Median Change From Baseline in Central Retinal Thickness, Central Retinal Lesion Thickness and Central Subfield Thickness in the Study Eye | Central retinal thickness, central retinal lesion thickness and central subfield thickness were determined using Spectral Domain Optical Coherence Tomography (SD-OCT). | The safety set included all subjects who received any amount of study drug. | Posted | Median | Full Range | micrometers | Day 1 to Day 113 |
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| Secondary | Median Change From Baseline in Macular Cube Volume in the Study Eye | Macular cube volume was determined using SD-OCT. | The safety set included all subjects who received any amount of study drug. | Posted | Median | Full Range | mm^3 | Day 1 to Day 113 |
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TEAEs were collected from Day 1 up to the final study visit at Day 113 (approximately 16 weeks).
The safety set included all subjects who received any amount of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 | 4 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 40 mg/mL) on Day 1. | 0 | 3 | 0 | 3 | 2 | 3 |
| EG001 | Cohort 2 | 10 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 100 mg/mL) on Day 1. | 0 | 3 | 0 | 3 | 2 | 3 |
| EG002 | Cohort 3 | 20 mg pegcetacoplan: Subjects received a single IVT injection of pegcetacoplan (100 μL of 200 mg/mL) on Day 1. | 0 | 7 | 0 | 7 | 4 | 7 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eye pain | Eye disorders | MedDRA 17.0 | Systematic Assessment |
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| Foreign body sensation in eyes | Eye disorders | MedDRA 17.0 | Systematic Assessment |
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| Retinal haemorrhage | Eye disorders | MedDRA 17.0 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 17.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 17.0 | Systematic Assessment |
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| Hordeolum | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
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| Albuminuria | Renal and urinary disorders | MedDRA 17.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Apellis Clinical Trial Information Line | Apellis Pharmaceuticals, Inc | 1-833-284-6361 | clinicaltrials@apellis.com |
| ID | Term |
|---|---|
| C000716074 | pegcetacoplan |
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| Male |
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| Hispanic or Latino |
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| Non-Hispanic or Latino |
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| Treatment-related AEs |
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| TEAEs leading to discontinuation |
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