title: A phase 1 study of KH902, a vascular endothelial growth factor receptor decoy, for exudative age-related macular degeneration.
abstract: OBJECTIVE
  To determine the safety, tolerability, and bioactivity of KH902, a fully human fusion protein containing key domains from vascular endothelial growth factor receptors 1 and 2 with human immunoglobulin Fc.
  
  
  METHODS
  Prospective, single-center, open-label, dose-escalating, interventional case series.
  
  
  METHODS
  Twenty-eight patients with choroidal neovascularization (CNV) resulting from exudative age-related macular degeneration (AMD) with lesion size of 12 disc areas or less and best-corrected visual acuity (VA) of 55 letters or worse.
  
  
  METHODS
  A single intravitreal injection of KH902 at 1 of 6 escalating doses if no dose-limiting toxicity (DLT) occurred through postinjection day 14 of the previous dose level. Follow-up examinations were performed on postinjection days 1, 3, 5, 7, 14, 28, and 42. The primary end point was at 42 days, and patients were monitored for an additional 6 weeks (12 weeks total).
  
  
  METHODS
  The primary safety measures were changes from baseline in VA, intraocular pressure (IOP), intraocular inflammation, and production of anti-KH902 antibody. Dose-limiting toxicity was defined as intraocular inflammation, elevated IOP, significantly reduced vision, or retinal hemorrhage within 42 days after injection. Bioactivity measures included mean change from baseline in VA, central retinal thickness, and total macular volume on optical coherence tomography and CNV changes on fluorescein angiography.
  
  
  RESULTS
  All patients completed the study with no DLT and no serious or drug-related adverse events. Ocular adverse events were mild to moderate in severity, including transient IOP elevation and injection-site subconjunctival hemorrhage after KH902 injections. No serum anti-KH902 antibodies were detected. On day 42 after injection, the mean change in VA from baseline was +19.6 letters with no subjects losing 1 letter or more and 57% of patients gaining 15 letters or more from baseline. The mean change in center point thickness from baseline was -77.2 μm and the mean decrease in CNV area was 12.6%.
  
  
  CONCLUSIONS
  No safety concerns were detected after a single, intravitreal injection of KH902 up to 3.0 mg in this phase 1 study. Bioactivity of KH902 was suggested with improvements in VA, reduction in central retinal thickness, and a decrease in CVN area in patients with CNV resulting from exudative AMD, indicating that further study is warranted.
authors.affiliation: Department of Ophthalmology, West China Hospital, Chengdu, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Junjun
authors.initials: J
authors.lastname: Zhang
authors.forename: Mi
authors.initials: M
authors.lastname: Yan
authors.forename: Delun
authors.initials: D
authors.lastname: Luo
authors.forename: Wenjin
authors.initials: W
authors.lastname: Zhu
authors.forename: Peter K
authors.initials: PK
authors.lastname: Kaiser
authors.forename: De-Chao
authors.initials: DC
authors.lastname: Yu
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D006801:Humans; D007429:Intraocular Pressure; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D020714:Maximum Tolerated Dose; D011379:Prognosis; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; C527363:KH902 fusion protein