title: A phase ia dose-escalation study of the anti-factor D monoclonal antibody fragment FCFD4514S in patients with geographic atrophy.
abstract: OBJECTIVE
  Multicenter, open-label, single-dose, dose-escalation Phase Ia study to determine the safety, tolerability, maximum tolerated dose, and immunogenicity of FCFD4514S, an antigen-binding fragment from a humanized monoclonal antibody directed against complement factor D, in patients with geographic atrophy.
  
  
  METHODS
  Eighteen patients with geographic atrophy (lesion size: ≥ 0.75 disk areas; best-corrected visual acuity: 20/125-20/400 Snellen equivalent) were sequentially enrolled and received 1 of 6 escalating doses of intravitreal FCFD4514S subject to dose-limiting toxicity criteria. Follow-up assessments (clinical examination, best-corrected visual acuity, intraocular pressure) were conducted at postadministration Days 1, 3, 7, 14, 30, 60, and 90. Serum pharmacokinetics, immunogenicity, and complement activity were also evaluated.
  
  
  RESULTS
  All patients completed the study with no reported FCFD4514S-related dose-limiting toxicities or ocular or systemic adverse events. The maximum tolerated dose for this study was 10 mg, the highest dose tested. No antitherapeutic antibody response or adverse effects on systemic complement activity were observed. Time to maximum serum concentration was 1 day to 3 days postdosing; serum terminal half-life was 5.9 days.
  
  
  CONCLUSIONS
  Single-dose intravitreal FCFD4514S administrations were safe and well tolerated and not associated with any study drug-related ocular or systemic adverse events. These data support a multidose safety and tolerability assessment of FCFD4514S in geographic atrophy.
authors.affiliation: *Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; †California Retina Consultants and Research Foundation, Santa Barbara, California; and ‡Genentech, Inc, South San Francisco, California.
authors.forename: Diana V
authors.initials: DV
authors.lastname: Do
authors.forename: Dante J
authors.initials: DJ
authors.lastname: Pieramici
authors.forename: Menno
authors.initials: M
authors.lastname: van Lookeren Campagne
authors.forename: Tatiana
authors.initials: T
authors.lastname: Beres
authors.forename: Michel
authors.initials: M
authors.lastname: Friesenhahn
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Erich C
authors.initials: EC
authors.lastname: Strauss
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011416:Complement Factor D / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D057092:Geographic Atrophy / Q000378:metabolism* / Q000628:therapy; D006207:Half-Life; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007429:Intraocular Pressure / Q000502:physiology; D058449:Intravitreal Injections; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D014792:Visual Acuity / Q000502:physiology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; C041323:immunoglobulin Facb fragment; D011416:Complement Factor D