CClinicalTrials.gg
TerminatedNCT03465709Updated Sep 16, 2020Results posted

Pegcetacoplan (APL-2) in Neovascular AMD

A Phase 1/2 interventional study of Pegcetacoplan in Neovascular Age-related Macular Degeneration, sponsored by Apellis Pharmaceuticals, Inc.. Terminated at 4 sites in United States. Open to participants aged 60 Years and older. Per ClinicalTrials.gov, last updated 2020-09-16.

Sponsored by Apellis Pharmaceuticals, Inc. · Phase 1/2, Interventional, and Treatment

Why this study was terminated
Apellis concluded that sufficient data were collected to meet the study objectives.
Phase
Phase 1/2
Study type
Interventional
Enrollment
17
Allocation
Not applicable
Ages
60 Years and older
Sex
All
01

Study summary

Safety Assessment of Pegcetacoplan in Patients with Neovascular AMD

02

Conditions studied

  • Neovascular Age-related Macular Degeneration
03

Who can participate

Ages eligible
60 Years and older
Sexes eligible
All
Accepts 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

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
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
17 participants (actual)

Study arms

  • Experimental
    Pegcetacoplan Study Drug

    Drug: Pegcetacoplan

Interventions

  • DrugPegcetacoplan

    Study Drug

    Also known as: APL-2

05

What researchers measure

Primary outcomes

  1. 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).

Secondary outcomes

  1. 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).

  2. 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).

06

Results

Posted Sep 16, 2020
Limitations and caveats
Exposure was shorter than expected as some subjects experienced intraocular inflammation in the study eye due to an identified impurity. The sponsor terminated the study early as sufficient data were collected to meet study objectives.

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.

Participant flow — Overall Study
Milestone15 mg Pegcetacoplan
Started17
Completed0
Not completed17
Withdrew: Study/site terminated by sponsor14
Withdrew: Withdrawal by subject3

Outcome measures

PrimaryNumber 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).
Reported as:
Count of participants · Participants
Number of Subjects Experiencing Ocular and Systemic Treatment-Emergent Adverse Events (TEAEs) Including by Maximum Severity
Participants15 mg Pegcetacoplan
Any TEAEs15
Ocular study eye TEAE14
Nonocular TEAE7
TEAE at least possibly related to study drug5
TEAE at least possibly related to injection8
Serious TEAEs4
TEAEs leading to study drug discontinuation1
TEAEs leading to death0
Maximum severity: mild6
Maximum severity: moderate6
Maximum severity: severe3
Maximum severity: life-threatening0
SecondaryMean 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).
Reported as:
Mean · micrometers
Mean Change From Baseline in SD-OCT Central Subfield Thickness (CST) up to 12 Months
micrometers15 mg Pegcetacoplan
Day 3012.9 ± 39.06
Day 6016.1 ± 66.99
Day 9015.1 ± 57.44
Day 12031.6 ± 68.33
Day 15034.8 ± 90.50
Day 18048.3 ± 92.21
Day 21018.5 ± 66.06
Day 24034.1 ± 66.35
Day 27049.2 ± 58.76
Day 30022.2 ± 73.29
Day 330-0.7 ± 57.17
Day 360-10.5 ± 48.67
SecondaryNumber 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).
Reported as:
Count of participants · Participants
Number of Subjects With Clinically Significant Change From Baseline in Physical Examination Findings, Vital Signs and Laboratory Parameters
Participants15 mg Pegcetacoplan
Physical examination findings2
Vital signs0
Laboratory parameters0

Adverse events

Collected over Day 1 up to end of study (up to 1 year).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
15 mg Pegcetacoplan: Ocular Study Eye0/17 (0%)3/17 (17.6%)13/17 (76.5%)
15 mg Pegcetacoplan: Ocular Fellow Eye0/17 (0%)0/17 (0%)3/17 (17.6%)
15 mg Pecgectacoplan: Non-ocular0/17 (0%)1/17 (5.9%)6/17 (35.3%)
Most frequent serious events
Most frequent serious events
Event15 mg Pegcetacoplan: Ocular Study Eye15 mg Pegcetacoplan: Ocular Fellow Eye15 mg Pecgectacoplan: Non-ocular
UveitisEye disorders2/170/170/17
Non-infectious endophthalmitisEye disorders1/170/170/17
HaemoptysisRespiratory, thoracic and mediastinal disorders0/170/171/17
Most frequent other events
Showing 10 of 30
Most frequent other events
Event15 mg Pegcetacoplan: Ocular Study Eye15 mg Pegcetacoplan: Ocular Fellow Eye15 mg Pecgectacoplan: Non-ocular
Intraocular pressure increasedInvestigations5/170/170/17
Conjunctival haemorrhageEye disorders3/170/170/17
UveitisEye disorders2/170/170/17
Vision blurredEye disorders2/170/170/17
Ocular hypertensionEye disorders2/170/170/17
PhotopsiaEye disorders2/170/170/17
Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/170/172/17
Eye painEye disorders1/170/170/17
Posterior capsule opacificationEye disorders1/170/170/17
Visual acuity reducedEye disorders1/170/170/17

Baseline characteristics

The safety set included all subjects who received at least 1 dose of pegcetacoplan.

Age, Continuous
Age, Continuous(years)15 mg Pegcetacoplan
Mean77.2 ± 8.76
Sex: Female, Male
Sex: Female, Male(Participants)15 mg Pegcetacoplan
Female7
Male10
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)15 mg Pegcetacoplan
Hispanic or Latino0
Not Hispanic or Latino17
Unknown or Not Reported0
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)15 mg Pegcetacoplan
White16
Native Hawaiian or Other Pacific Islander1
07

Study locations

4 sites
  • Apellis Clinical Site
    Beverly Hills, California 90211, United States
  • Apellis Clinical Site
    Hagerstown, Maryland 21740, United States
  • Apellis Clinical Site
    Cleveland, Ohio 44122, United States
  • Apellis Clinical Site
    Houston, Texas 77030, United States
08

References and documents

Study documents

  • Study protocol · Aug 3, 2018
  • Statistical analysis plan · Jul 3, 2019

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03465709
Lead sponsor
Apellis Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
Mar 14, 2018
Start date
Feb 14, 2018
Primary completion
Apr 5, 2019
Completion
Apr 5, 2019
Results posted
Sep 16, 2020
Last update
Sep 16, 2020

Study contacts

Federico Grossi, MD, PhD
study director · Apellis Pharmaceuticals, Inc.

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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