Neovascular Age-Related Macular DegenerationPhase 1ASAP IINCT02461771

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

A Phase 1 study testing Pegcetacoplan in people with Neovascular Age-Related Macular Degeneration, run by Apellis Pharmaceuticals, Inc. at 4 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 50 years and older
Conditions the study is for: Neovascular Age-Related Macular Degeneration
What is being tested?: Pegcetacoplan
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 4 sitesin 2 countries
Study dates: 28 Jan 2015to 8 Mar 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 50 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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:
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
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

Who cannot join

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

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History of treatment for CNV:
Previous PDT treatment within 30 days prior to enrollment in the study
Previous extrafoveal or juxtafoveal thermal laser photocoagulation within 30 days prior to enrollment in the study
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

Trial locations and contacts

4 sites in 2 countries.

Country

City, postcode or hospital

4 sites in 2 countries

United States3 sites

United States, California
Beverly Hills, California, 90211
United States, Florida
Miami, Florida, 33136
United States, New Hampshire
Portsmouth, New Hampshire, 03801

Other trials in United States

Australia1 site

Australia, New South Wells
Parramatta, New South Wales, 2150

Other trials in Australia

About this study

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

Conditions: Neovascular Age-Related Macular Degeneration
Being tested: Pegcetacoplan
Keywords: AMD, Wet AMD, Neovascular AMD

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PegcetacoplanDrug
Also called APL-2
On treatment day, subjects will be administered a single 100 μL IVT injection of pegcetacoplan at the dose corresponding to their treatment assignment.

Study groups in NCT02461771
Study group	Role	What they receive
Pegcetacoplan Cohort 1	Experimental	4 mg of pegcetacoplan 100 μL IVT injection Receives: Drug: Pegcetacoplan
Pegcetacoplan Cohort 2	Experimental	10 mg of pegcetacoplan 100 μL IVT injection Receives: Drug: Pegcetacoplan
Pegcetacoplan Cohort 3	Experimental	20 mg of pegcetacoplan 100 μL IVT injection Receives: Drug: Pegcetacoplan

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Predose (screening), postdose Day 3 to Day 113
Maximum Observed Serum Concentration (Cmax)
The median Cmax is presented for each cohort.
Measured: Predose (screening), postdose Day 3 to Day 113
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.
Measured: 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.
Measured: Predose (screening), postdose Day 3 to Day 113

Secondary outcomes (3)

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.
Measured: 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).
Measured: 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.
Measured: Day 1 to Day 113

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Jan 20158 Mar 2016

First posted3 Jun 2015 (estimated)
Study start28 Jan 2015
Primary completion8 Mar 2016
Study completion8 Mar 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Neovascular Age-Related Macular DegenerationStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02461771
Sponsor's protocol ID: POT-CP043014
Acronym: ASAP II
Status last verified: Sep 2020
First submitted: 2 Jun 2015
Last updated: 6 Oct 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
A Study of 36-Week Refill Exchanges of Port Delivery System (PDS) With Ranibizumab in nAMD
Neovascular Age-related Macular Degeneration
Active, not recruitingObservational study
Real World Evidence in China: Faricimab Use in Diabetic Macular Edema, Retinal Vein Occlusion, and Neovascular Age-Related Macular Degeneration (The Farseeing Study)
Diabetic Macular Edema, Neovascular Age-related Macular Degeneration
Active, not recruitingPhase 1/2
Phase 1/2 Study of VOY-101 in Patients With Advanced Non-Neovascular Age-Related Macular Degeneration
Age-Related Macular Degeneration, Geographic Atrophy
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Tarcocimab Tedromer and Tabirafusp Tedromer Compared to Aflibercept in Participants With Neovascular (Wet) Age-related Macular Degeneration (wAMD) - DAYBREAK
Wet Age-related Macular Degeneration
Not yet recruitingPhase 2
A Study to Evaluate the Efficacy and Safety of VIS-101 in Participants With Neovascular Age-Related Macular Degeneration
Neovascular Age Related Macular Degeneration(nAMD)

All Neovascular Age-Related Macular Degeneration trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Assessment of Safety, Tolerability and Pharmacokinetics of Intravitreal APL-2 Therapy for Neovascular Age-Related Macular Degeneration (AMD)
ClinicalTrials.gov ID: NCT02461771
Acronym / sponsor ID: ASAP II / POT-CP043014
Conditions: Neovascular Age-Related Macular Degeneration
Keywords: AMD, Wet AMD, Neovascular AMD
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: Apellis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: 28 Jan 2015 (actual)
Primary completion: 8 Mar 2016 (actual)
Study completion: 8 Mar 2016 (actual)
First posted: 3 Jun 2015 (estimated)
Results: Posted 6 Oct 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Pegcetacoplan Cohort 1	Experimental	Drug: Pegcetacoplan4 mg of pegcetacoplan 100 μL IVT injection
Pegcetacoplan Cohort 2	Experimental	Drug: Pegcetacoplan10 mg of pegcetacoplan 100 μL IVT injection
Pegcetacoplan Cohort 3	Experimental	Drug: Pegcetacoplan20 mg of pegcetacoplan 100 μL IVT injection

Who may qualify

Ages: 50 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

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)

Key exclusion criteria (12 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PegcetacoplanAlso: APL-2On treatment day, subjects will be administered a single 100 μL IVT injection of pegcetacoplan at the dose corresponding to their treatment assignment.	Drug	Pegcetacoplan Cohort 1, Pegcetacoplan Cohort 2, Pegcetacoplan Cohort 3

Primary outcome

Number of Subjects Who Experienced Ocular and Systemic Adverse Events (AEs), Including by Severity
Time frame: 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)
Time frame: 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])
Time frame: 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.
Median Dose Normalized AUC(0-t)
Time frame: 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)
Time frame: Predose (screening), postdose Day 3 to Day 113
The median Cmax is presented for each cohort.
Median Dose Normalized Cmax
Time frame: 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.
Median Time to the Maximum Measured Serum Concentration (Tmax)
Time frame: 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.

3 secondary outcomes

Median Change From Baseline in Visual Acuity for the Study Eye
Time frame: 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
Time frame: Day 1 to Day 113
Median Change From Baseline in Macular Cube Volume in the Study Eye
Time frame: Day 1 to Day 113

Results and safety

Results posted to the registry on 6 Oct 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1	3	3
Cohort 2	3	3
Cohort 3	7	7

Primary outcome: Number of Subjects Who Experienced Ocular and Systemic Adverse Events (AEs), Including by Severity

Time frame: Day 1 to Day 113. Count of participants. Unit: Participants

Measure	Cohort 1 n = 3	Cohort 2 n = 3	Cohort 3 n = 7
All TEAEs	2	2	4
Ocular TEAEs	1	1	2
Treatment-related AEs	0	0	2
Serious AEs	0	0	0
TEAEs leading to discontinuation	0	0	0

Population analysed: The safety set included all subjects who received any amount of study drug.

Primary outcome: Number of Dose Limiting Toxicities (DLTs)

Time frame: Day 1 to Day 15. Number. Unit: Number of DLTs

Measure	Cohort 1 n = 3	Cohort 2 n = 3	Cohort 3 n = 7
Value	0	0	0

Population analysed: The safety set included all subjects who received any amount of study drug.

Primary outcome: Median Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-t])

Time frame: Predose (screening), postdose Day 3 to Day 113. Median (Full Range). Unit: micrograms*day/milliliter (μg*day/mL)

Measure	Cohort 1 n = 3	Cohort 2 n = 3	Cohort 3 n = 7
Value	11.89 (11.49 to 13.90)	29.95 (24.27 to 53.59)	69.53 (55.06 to 86.92)

Population analysed: 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).

Primary outcome: Median Dose Normalized AUC(0-t)

Time frame: Predose (screening), postdose Day 3 to Day 113. Median (Full Range). Unit: (μg*day/mL)/respective mg dose

Measure	Cohort 1 n = 3	Cohort 2 n = 3	Cohort 3 n = 7
Value	2.97 (2.87 to 3.47)	3.00 (2.43 to 5.36)	3.48 (2.75 to 4.35)

Population analysed: 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).

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: TEAEs were collected from Day 1 up to the final study visit at Day 113 (approximately 16 weeks).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Cohort 2	0 of 3 (0%)	2 of 3 (66.7%)	0 of 3
Cohort 3	0 of 7 (0%)	4 of 7 (57.1%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Neovascular Age-Related Macular Degeneration

RecruitingPhase 3
A Study of 36-Week Refill Exchanges of Port Delivery System (PDS) With Ranibizumab in nAMD
Neovascular Age-related Macular Degeneration
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Real World Evidence in China: Faricimab Use in Diabetic Macular Edema, Retinal Vein Occlusion, and Neovascular Age-Related Macular Degeneration (The Farseeing Study)
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Federico Grossi, MD PhD study director

Apellis Pharmaceuticals, Inc.

4 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pegcetacoplan in people with Neovascular Age-Related Macular Degeneration, run by Apellis Pharmaceuticals, Inc. at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects Who Experienced Ocular and Systemic Adverse Events (AEs), Including by Severity (time frame: Day 1 to Day 113). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02461771.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2020.