June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
A Phase 1b Multi-Center, Open Label, Single-Arm Safety Study of Intravitreal Pegcetacoplan Supporting the Phase 3 DERBY and OAKS Studies for Geographic Atrophy: A Solution to “Tarmac Delay"
Author Affiliations & Notes
  • Nathan Steinle
    Ophthalmology, Retina Associates of Kentucky, Kentucky, United States
  • jeffrey heier
    Ophthalmology, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Rishi P Singh
    Ophthalmology, Cleveland Clinic, Cleveland, Ohio, United States
  • David S Boyer
    Ophthalmology, Retina-Vitreous Associates Medical Group, Los Angeles, California, United States
  • Eleonora M Lad
    Ophthalmology, Duke University Department of Ophthalmology, Durham, North Carolina, United States
  • Ravi Metlapally
    Apellis Pharmaceuticals Inc, Crestwood, Kentucky, United States
  • Ramiro Ribiero
    Apellis Pharmaceuticals Inc, Crestwood, Kentucky, United States
  • Charles Clifton Wykoff
    Ophthalmology, Houston Methodist, Houston, Texas, United States
  • Chris Holmes
    Apellis Pharmaceuticals Inc, Crestwood, Kentucky, United States
  • Footnotes
    Commercial Relationships   Nathan Steinle, Alimera (S), Alimera Sciences (C), Apellis (C), Genentech (C), Genentech (S), Notal Vision (S), Novartis (C), Novartis (S), Opthea (C), Regeneron (C), Regeneron (S), Regeneron (I), Regenxbio (C), Vortex Surgical (C), Vortex Surgical (I), Zeiss (C); jeffrey heier, 4DMT (C), Adverum (C), Aerie (C), Aerpio (C), Aideyra (C), Allegro (C), Apellis (C), Asclepix (C), Aviceda (C), Bayer (C), Galimedix (C), Genetech (C), Graybug (C), Gyroscope (C), Hemera (C), Iveric (C), Janssen R&D (C), Kanghong (C), Kodiak (C), NGM (C), Novartis (C), Regeneron (C), Regenxbio (C), Stealth (C); Rishi Singh, Aerie (F), Alcon (C), Apellis (C), Apellis (F), Bausch + Lomb (C), Genentech (C), Graybug (F), Novartis (C), Regeneron (C), Zeiss (C); David Boyer, Acucela (C), Adverum (C), Aerie (C), Aerpio (C), Alcon (C), Alkahest (C), Allegro (C), Allegro (I), Allergan (C), Amydis (C), Annexon Biosciences (C), Apellis (C), AsclepiX (C), Bausch and Lomb (C), Bayer (C), Beohringer-Ingelheim (C), Biogen Inc (C), BioMotiv (C), Cell Care (C), Chengdu Kanghong Biotechnology Co (C), Clearside Biomedical (C), Daiichi Sanko Co (C), DigiSight (I), Eyepoint (C), Genentech (C); Eleonora Lad, Apellis (C), Galimedix (C), Gemini Therapeutics (C), Novartis (F), Retrotope (C), Roche (F), Roche (C); Ravi Metlapally, Apellis (E), Biogen (E); Ramiro Ribiero, Apellis (E); Charles Wykoff, Acucela (C), Adverum (C), Aerpio (C), Alimera Sciences (C), Allegro (C), Allergan (C), Alnylam (C), Apellis (C), Arctic Vision (C), Bausch + Lomb (C), Bayer (C), Chengdu Kanghong Biotech (C), Clearside Biomedical (C), Corcept Therapeutics (C), DORC (C), EyePoint Pharmaceuticals (C), Genentech (C), Gyroscope (C), Iveric Bio (C), Kodiak Sciences (C), Merck (C), NGM Biopharmaceticals (C), Notal Vision (C), Novartis (C), ONL Therapeutics (C); Chris Holmes, Apellis (E)
  • Footnotes
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Investigative Ophthalmology & Visual Science June 2021, Vol.62, 278. doi:
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      Nathan Steinle, jeffrey heier, Rishi P Singh, David S Boyer, Eleonora M Lad, Ravi Metlapally, Ramiro Ribiero, Charles Clifton Wykoff, Chris Holmes; A Phase 1b Multi-Center, Open Label, Single-Arm Safety Study of Intravitreal Pegcetacoplan Supporting the Phase 3 DERBY and OAKS Studies for Geographic Atrophy: A Solution to “Tarmac Delay". Invest. Ophthalmol. Vis. Sci. 2021;62(8):278.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Describe the origin and interim results of a phase 1b safety study, APL2-103, supporting two large phase 3 studies of intravitreal pegcetacoplan for geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Methods : In December 2018, the phase 3 DERBY and OAKS studies of intravitreal pegcetacoplan for GA were voluntarily paused due to transient intraocular inflammation (IOI, n=4) after dosing with a new formulation developed for phase 3 trials. An investigation to determine the exact cause was conducted. Quality review of the manufacturing process revealed an impurity in the active pharmaceutical ingredient introduced during scale up. Additional manufacturing steps to eliminate the impurity were implemented, and the resulting product was tested in several animal studies. APL2-103, a 24-month phase 1b, open-label, single-arm safety study of monthly pegcetacoplan was initiated in GA subjects with low vision (Snellen 20/200 to 20/800) before further dosing in phase 3 trials.

Results : All four patients with IOI in the phase 3 studies recovered fully (mean BCVA before: 47.5 letters [range 38-67] and after: 45.5 letters [29-68]). Phase 3 studies were re-initiated in March 2019 after a drug product lot without the impurity revealed no signs of investigator-assessed IOI in 10 subjects who completed a 7-day follow-up evaluation in APL2-103 across 4 clinical sites. APL2-103 continues supporting drug product lot evaluation before use in DERBY/OAKS. Safety findings in APL2-103 after phase 3 re-initiation were consistent with all previous and ongoing intravitreal pegcetacoplan programs. In APL2-103, one patient developed new-onset exudation, and no cases of IOI were observed with the phase 3 formulation. An exploratory interim efficacy analysis of APL2-103 in bilateral GA patients with 12 (n=9) and 18 (n=7) months of follow up revealed that the GA growth rate in pegcetacoplan-treated eyes was slower than untreated fellow eyes by 31% at month 12 and 52% at month 18.

Conclusions : The likely root cause of intraocular inflammation was identified and eliminated. These findings highlight the value of ensuring safety following manufacturing or formulation changes. APL2-103 continues to support the fully enrolled phase 3 studies, with an acceptable safety profile.

This is a 2021 ARVO Annual Meeting abstract.

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