September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
A Proof of Concept Study of Intravitreal (IVT) LFG316 In Patients with Neovascular Age Realted Macular Degeneration (nAMD)
Author Affiliations & Notes
  • Ron P Gallemore
    Dept Cell Biology and Histology, Retina Macula Institute, Torrance, California, United States
  • Michael J Elman
    Elman Retina, Baltimore, Maryland, United States
  • Mark Milton
    Novartis, Mission Viejo, California, United States
  • Parisa Zamiri
    Novartis, Mission Viejo, California, United States
  • Cynthia L Grosskreutz
    Novartis, Mission Viejo, California, United States
  • Footnotes
    Commercial Relationships   Ron Gallemore, None; Michael Elman, Alcon (F), Allergan (F), Clearside (F), Genentecth (F), Jaeb Center (F), Merck (F), Notal Vision (I), Novartis (F), Ohr Pharmaceuticals (F), Tyrogenix (F); Mark Milton, None; Parisa Zamiri, None; Cynthia Grosskreutz, None
  • Footnotes
    Support  NCT01535950 FPFV
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4986. doi:
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      Ron P Gallemore, Michael J Elman, Mark Milton, Parisa Zamiri, Cynthia L Grosskreutz; A Proof of Concept Study of Intravitreal (IVT) LFG316 In Patients with Neovascular Age Realted Macular Degeneration (nAMD). Invest. Ophthalmol. Vis. Sci. 2016;57(12):4986.

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

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Abstract

Purpose : The risk of developing AMD is strongly associated with alleles in genes encoding proteins in the alternative complement pathway. LFG316 is a fully human antibody that inhibits Complment factor 5 (C5)’s ability to form C5 convertase. In a multicenter, randomized, sham-controlled, repeat-dose study, the safety, tolerability, and efficacy of IVT LFG316 were assessed in patients with nAMD.

Methods : 45 patients with active nAMD were randomized in a 2:1 ratio to receive either 3 monthly doses of 5 mg/50 μL LFG316 (n=30) or 3 monthly sham injections (n=15). They were followed for 113 days. The primary objective was to evaluate the rate at which patients required retreatment with an anti-VEGF therapy by day 85. The key secondary objectives were safety and changes in best corrected visual acuity (BCVA) and central retinal thickness (CRT). Assessments included clinical and laboratory evaluations, BCVA, intraocular pressure measurement, dilated biomicroscopy, fundus photography, fluorescein angiography, serum pharmacokinetics (total LFG316), pharmacodynamics (total C5), and immunogenicity.

Results : The majority of patients were Caucasian (96%) and female (68%). Monthly treatment with IVT LFG316 was safe and well tolerated. The rate of anti-VEGF retreatment (mean ± SD) was 0.10 ± 0.097 per week in the LFG316 treatment arm and 0.08 ± 0.078 per week in the sham treatment arm. The adjusted mean [95% CI] change in CRT was -27.6 [-113.0, 57.8] μm for the LFG316 treatment arm and -55.1 [-173.5, 63.3] μm for the sham treatment arm. The difference in change in CRT between the two treatment arms was not statistically significant (p= 0.7). After IVT administration very low levels of LFG316 (the highest observed concentration was 1.49 µg/mL) was detected in the majority of serum samples up to 14 days post dose and in approximately 40% of patients at 28 days post dose. The serum LFG316 concentrations were always much lower than serum C5 concentrations (~160 µg/mL), indicating that IVT doses did not systemically suppress complement activity. Anti-LFG316 antibodies were not detected in any patient.

Conclusions : Monthly IVT doses of 5 mg of LFG316 were well tolerated and safe. There were no statistically significant differences in the rate of anti-VEGF retreatment or in changes in BCVA or CRT between the two treatment groups.

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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