September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Ocular Coherence Tomography Used to Support an Investigational New Drug Application for a C3 Complement Inhibitor Targeting Macular Degeneration.
Author Affiliations & Notes
  • Margaret E Collins
    Ophthalmology, Charles River, Reno, Nevada, United States
  • Jason S Slakter
    NYU Medical School, Great Neck, New York, United States
  • Robert Munger
    Animal Ophthalmology, Dallas, Texas, United States
  • Patty Wells
    Ophthalmology, Charles River, Reno, Nevada, United States
  • Collin Kolodziej
    Ophthalmology, Charles River, Reno, Nevada, United States
  • Pascal Deschatelets
    Potentia Pharmaceuticals, Inc, Crestwood, Kentucky, United States
  • Ray Stoll
    Stoll & Associates, Storrs Mansfield, Connecticut, United States
  • Footnotes
    Commercial Relationships   Margaret Collins, Charles River (E); Jason Slakter, NYU (E); Robert Munger, Animal Ophthalmology (E); Patty Wells, Charles River (E); Collin Kolodziej, Charles River (E); Pascal Deschatelets, Potentia Pharmaceuticals (E); Ray Stoll, Stoll & Associates (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4251. doi:
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    • Get Citation

      Margaret E Collins, Jason S Slakter, Robert Munger, Patty Wells, Collin Kolodziej, Pascal Deschatelets, Ray Stoll; Ocular Coherence Tomography Used to Support an Investigational New Drug Application for a C3 Complement Inhibitor Targeting Macular Degeneration.
      . Invest. Ophthalmol. Vis. Sci. 2016;57(12):4251.

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

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Abstract

Purpose : The objectives of this study were to determine the potential toxicity of APL-2 when administered by intravitreal injection every 4 weeks for 9 months to cynomolgus monkeys, to determine the toxicokinetic characteristics of APL-2, and to evaluate OCT as a non-invasive method of assessing the eyes.

Methods : APL-2, a peptide conjugate that inhibits complement C3, was assessed for 9 months following monthly intravitreal (IVT) injection (50 or 100 mL) to cynomolgus monkeys at dose levels of 3.1, 12.4, and 24.8 mg/eye. Vehicle (5% Dextrose, USP) and control article (unfunctionalized conjugate backbone) groups were included. Clinical signs, body weights, ophthalmology, electroretinography (ERG), tonometry, spectral domain optical coherence tomography (SD-OCT), clinical pathology, and bioanalysis parameters (serum bioanalysis, anti-drug antibody, CH50) were evaluated. At the interim time point, no necropsy occurred, but OCT was used to evaluate the eyes. At the end of the study, OCT and histology were used to evaluate the eyes.

Results : Procedure-related ocular findings included clinical signs of eye opacity and pupil dilation, ophthalmic findings of aqueous flare and cells, and vitreous haze, and decreased intraocular pressure. All findings were in one eye of a single 24.8 mg/eye/dose animal, except for pupil dilation (also noted in one vehicle-treated animal). Cells were noted in the anterior vitreous of control article and APL-2 animals.
Increases in serum exposure for the 12.4 mg/eye group were slightly less than dose proportional relative to the 3.1 mg/eye group, but were generally dose proportional in the 24.8 mg/eye group were relative to the 12.4 mg/eye group. No sex differences or antigenicity were detected for APL-2 or the conjugate backbone.

Conclusions : SD-OCT evaluation was used as the primary means of assessing the retina at the interim time point and demonstrated no test article-related retinal changes. Histological evaluation at the end of 9 months confirmed the OCT findings. The use of OCT was a pivotal component of an IND that was opened in November, 2014. On the basis of these findings, the Phase I clinical trials were initiated.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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