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NCT02503332: FILLY

Study of Pegcetacoplan (APL-2) Therapy in Patients With Geographic Atrophy

Completed Phase 2 Results posted Last updated 6 October 2020
What this trial tests

Phase 2 trial testing Pegcetacoplan in Geographic Atrophy in 246 participants. Completed in 17 January 2018.

Timeline
24 September 2015
Primary endpoint
14 July 2017
17 January 2018

Quick facts

Lead sponsorApellis Pharmaceuticals, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designsingle group
Maskingsingle
Primary purposetreatment
Enrollment246
Start date24 September 2015
Primary completion14 July 2017
Estimated completion17 January 2018
Sites46 locations across New Zealand, United States, Australia

Drugs / interventions tested

Conditions studied

Sponsor

Apellis Pharmaceuticals, Inc. — full company profile →

Who can join

50 and older, any sex, with Geographic Atrophy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Least Square (LS) Mean Change From Baseline in Square Root GA Lesion Size in the Study Eye at Month 12 Primary · Baseline (screening) and Month 12.

The square root GA lesion size (i.e. transformed area of GA) was measured by FAF photographs. Baseline was defined as the last available, non-missing observation prior to first study drug administration.

GroupValue95% CI
Pegcetacoplan Monthly0.26± 0.025
Pegcetacoplan EOM0.28± 0.026
Sham Pooled0.35± 0.025
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) in the Study Eye, Including by Severity Primary · From the time of first study drug administration (Day 1) up to Month 12 (Data cut-off date).

A TEAE was defined as any adverse event (AE) that commenced or worsened on or after time of first study drug administration up to 60 days beyond last dose of study drug. A treatment-related TEAE was defined as a TEAE with a relationship to study drug of possibly related or probably related or not reported. Severity of TEAEs were categorized as mild; moderate; severe; life-threatening or death related to TEAE, according to Common Terminology Criteria for AEs v4.03. A TEAE of special interest (TEAESI) was defined as a TEAE of scientific and medical concern specific to pegcetacoplan, whether seri

TEAEs
GroupValue95% CI
Pegcetacoplan Monthly65
Pegcetacoplan EOM47
Sham Pooled42
Treatment-related TEAEs
GroupValue95% CI
Pegcetacoplan Monthly21
Pegcetacoplan EOM11
Sham Pooled0
Serious TEAEs
GroupValue95% CI
Pegcetacoplan Monthly4
Pegcetacoplan EOM2
Sham Pooled1
TEAEs with mild intensity
GroupValue95% CI
Pegcetacoplan Monthly36
Pegcetacoplan EOM30
Sham Pooled28
TEAEs with moderate intensity
GroupValue95% CI
Pegcetacoplan Monthly23
Pegcetacoplan EOM14
Sham Pooled11
TEAEs with severe intensity
GroupValue95% CI
Pegcetacoplan Monthly6
Pegcetacoplan EOM3
Sham Pooled3
TEAEs with life-threatening intensity
GroupValue95% CI
Pegcetacoplan Monthly0
Pegcetacoplan EOM0
Sham Pooled0
Death related to TEAEs
GroupValue95% CI
Pegcetacoplan Monthly0
Pegcetacoplan EOM0
Sham Pooled0
LS Mean Change From Baseline in Untransformed GA Lesion Size in the Study Eye at Month 12 Secondary · Baseline (Day 1) and Month 12.

The untransformed area of GA was measured by FAF. Baseline is defined as the last available, non-missing observation prior to first study drug administration.

GroupValue95% CI
Pegcetacoplan Monthly1.49± 0.161
Pegcetacoplan EOM1.69± 0.168
Sham Pooled2.12± 0.161
LS Mean Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score of the Study Eye at Month 12 Secondary · Baseline (Day 1) and Month 12.

The 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.

GroupValue95% CI
Pegcetacoplan Monthly-3.31± 1.352
Pegcetacoplan EOM-5.78± 1.398
Sham Pooled-4.36± 1.364
LS Mean Change From Baseline in Low Luminance BCVA (LL-BCVA) Score in the Study Eye at Month 12 Secondary · Baseline (Day 1) and Month 12.

The LL-BCVA was measured by placing a 2.0-log-unit neutral density filter over the best correction and having the participant read the normally illuminated ETDRS chart. The score ranges from 0 to 100 letters, lower number indicating worse vision; a positive value of change from baseline indicates visual acuity gain and a negative value indicates visual acuity loss.

GroupValue95% CI
Pegcetacoplan Monthly-2.73± 1.145
Pegcetacoplan EOM-3.21± 1.184
Sham Pooled-0.55± 1.150
LS Mean Change From Baseline in Low Luminance VA (LL-VA) Deficit Score in the Study Eye at Month 12 Secondary · Baseline (Day 1) and Month 12.

The LL-VA deficit score is calculated as BCVA score minus LL-BCVA score. The LL-VA deficit score ranges from 0 to 100 letters, lower number indicating worse deficit.

GroupValue95% CI
Pegcetacoplan Monthly-0.76± 1.382
Pegcetacoplan EOM-2.40± 1.424
Sham Pooled-3.72± 1.385
LS Mean Change From Baseline in Distance of GA Lesion From the Fovea (Foveal Encroachment) in the Study Eye at Month 12 Secondary · Baseline (Day 1) and Month 12.

The foveal encroachment in the study eye was measured by FAF. Baseline is defined as the last available, non-missing observation prior to first study drug administration.

GroupValue95% CI
Pegcetacoplan Monthly-0.04± 0.011
Pegcetacoplan EOM-0.04± 0.012
Sham Pooled-0.06± 0.011
Number of Subjects With Any Macular Neovascularization (MNV) TEAEs in the Study Eye Secondary · From the time of first study drug administration (Day 1) up to Month 12 (Data cut-off date).

The number of subjects with any MNV TEAEs in the study eye was identified via clinical review of all ocular TEAEs.

GroupValue95% CI
Pegcetacoplan Monthly14
Pegcetacoplan EOM5
Sham Pooled1

Adverse events — posted to ClinicalTrials.gov

Time frame: TEAE data is reported from the time of first study drug administration (Day 1) up to Month 12 (Data cut-off date).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pegcetacoplan Monthly: Ocular Study Eye
Serious: 4/86 (5%)
Deaths: 0/86
Pegcetacoplan EOM: Ocular Study Eye
Serious: 2/79 (3%)
Deaths: 0/79
Sham Pooled: Ocular Study Eye
Serious: 1/81 (1%)
Deaths: 0/81
Pegcetacoplan Monthly: Ocular Fellow Eye
Serious: 0/86 (0%)
Deaths: 0/86
Pegcetacoplan EOM: Ocular Fellow Eye
Serious: 0/79 (0%)
Deaths: 0/79
Sham Pooled: Ocular Fellow Eye
Serious: 1/81 (1%)
Deaths: 0/81
Pegcetacoplan Monthly: Non-ocular
Serious: 12/86 (14%)
Deaths: 0/86
Pegcetacoplan EOM: Non-ocular
Serious: 23/79 (29%)
Deaths: 2/79
Sham Pooled: Non-ocular
Serious: 16/81 (20%)
Deaths: 2/81

Serious adverse events (74 terms)

ReactionSystemPegcetacoplan Monthly: Ocu…Pegcetacoplan EOM: Ocular …Sham Pooled: Ocular Study …Pegcetacoplan Monthly: Ocu…Pegcetacoplan EOM: Ocular …Sham Pooled: Ocular Fellow…Pegcetacoplan Monthly: Non…Pegcetacoplan EOM: Non-ocu…Sham Pooled: Non-ocular
Cardiac failure congestiveCardiac disorders
FallInjury, poisoning and procedural complications
EndophthalmitisInfections and infestations
Atrial fibrillationCardiac disorders
Multiple organ dysfunction syndromeGeneral disorders
PneumoniaInfections and infestations
Intraocular pressure increasedInvestigations
Retinal detachmentEye disorders
Dry age-related macular degenerationEye disorders
Acute myocardial infarctionCardiac disorders
Angina unstableCardiac disorders
Cardiac failure acuteCardiac disorders
Coronary artery diseaseCardiac disorders
Coronary artery occlusionCardiac disorders
Coronary artery stenosisCardiac disorders
Mitral valve calcificationCardiac disorders
Myocardial infarctionCardiac disorders
Sinus node dysfunctionCardiac disorders
Supraventricular tachyarrhythmiaCardiac disorders
DiarrhoeaGastrointestinal disorders
GastritisGastrointestinal disorders
Inguinal herniaGastrointestinal disorders
Oesophageal obstructionGastrointestinal disorders
Peptic ulcerGastrointestinal disorders
Rectal haemorrhageGastrointestinal disorders
Other adverse events (15 terms — click to expand)

ReactionSystemPegcetacoplan Monthly: Ocu…Pegcetacoplan EOM: Ocular …Sham Pooled: Ocular Study …Pegcetacoplan Monthly: Ocu…Pegcetacoplan EOM: Ocular …Sham Pooled: Ocular Fellow…Pegcetacoplan Monthly: Non…Pegcetacoplan EOM: Non-ocu…Sham Pooled: Non-ocular
Vitreous floatersEye disorders
Conjunctival haemorrhageEye disorders
Eye painEye disorders
Neovascular age-related macular degenerationEye disorders
Visual impairmentEye disorders
Urinary tract infectionInfections and infestations
Intraocular pressure increasedInvestigations
Viral upper respiratory tract infectionInfections and infestations
FallInjury, poisoning and procedural complications
HypertensionVascular disorders
Vitreous detachmentEye disorders
Dry eyeEye disorders
NauseaGastrointestinal disorders
SinusitisInfections and infestations
Visual acuity reducedEye disorders

Most-reported serious reactions: Cardiac failure congestive, Fall, Endophthalmitis, Atrial fibrillation, Multiple organ dysfunction syndrome, Pneumonia, Intraocular pressure increased, Retinal detachment.

Data from ClinicalTrials.gov NCT02503332 adverse events section.

Sponsor's own description

The primary objectives of the study are to assess the safety, tolerability and evidence of activity of multiple intravitreal (IVT) injections of pegcetacoplan in subjects with Geographic Atrophy associated with Age-Related Macular Degeneration (AMD).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. New insights into the immune functions of complement.
    Reis ES, Mastellos DC, Hajishengallis G, Lambris JD. · · 2019 · cited 357× · PMID 31048789 · DOI 10.1038/s41577-019-0168-x
  2. The renaissance of complement therapeutics.
    Ricklin D, Mastellos DC, Reis ES, Lambris JD. · · 2018 · cited 305× · PMID 29199277 · DOI 10.1038/nrneph.2017.156
  3. THE PATHOPHYSIOLOGY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION AND THE COMPLEMENT PATHWAY AS A THERAPEUTIC TARGET.
    Boyer DS, Schmidt-Erfurth U, van Lookeren Campagne M, Henry EC, et al · · 2017 · cited 181× · PMID 27902638 · DOI 10.1097/iae.0000000000001392
  4. Treatments for dry age-related macular degeneration: therapeutic avenues, clinical trials and future directions.
    Cabral de Guimaraes TA, Daich Varela M, Georgiou M, Michaelides M. · · 2022 · cited 135× · PMID 33741584 · DOI 10.1136/bjophthalmol-2020-318452
  5. CLINICAL ENDPOINTS FOR THE STUDY OF GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.
    Sadda SR, Chakravarthy U, Birch DG, Staurenghi G, et al · · 2016 · cited 114× · PMID 27652913 · DOI 10.1097/iae.0000000000001283
  6. Modulation of three key innate immune pathways for the most common retinal degenerative diseases.
    Akhtar-Schäfer I, Wang L, Krohne TU, Xu H, et al · · 2018 · cited 100× · PMID 30224384 · DOI 10.15252/emmm.201708259
  7. The Challenges and Promise of Complement Therapeutics for Ocular Diseases.
    Park DH, Connor KM, Lambris JD. · · 2019 · cited 87× · PMID 31156618 · DOI 10.3389/fimmu.2019.01007
  8. New milestones ahead in complement-targeted therapy.
    Ricklin D, Lambris JD. · · 2016 · cited 73× · PMID 27321574 · DOI 10.1016/j.smim.2016.06.001

Verify or expand the search:

Other trials of Pegcetacoplan

Trials testing the same drug.

Other recruiting trials for Geographic Atrophy

Currently open trials in the same condition.

Other Apellis Pharmaceuticals, Inc. trials

Trials by the same sponsor.

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