title: Treatment of exudative age-related macular degeneration with a designed ankyrin repeat protein that binds vascular endothelial growth factor: a phase I/II study.
abstract: OBJECTIVE
  To evaluate the safety, tolerability and bioactivity of ascending doses of MP0112, a designed ankyrin repeat protein (DARPin) that binds with high affinity to vascular endothelial growth factor-A (VEGF-A), in treatment-naive patients with exudative age-related macular degeneration (AMD).
  
  
  METHODS
  Phase I/II, open-label, multicenter, dose-escalation study.
  
  
  METHODS
  Patients were to receive a single intravitreal injection of MP0112 at doses ranging from 0.04 to 3.6 mg and be monitored for 16 weeks for safety, efficacy, pharmacokinetics, and dose response.
  
  
  RESULTS
  Altogether, 32 patients received a single injection of MP0112. The maximum tolerated dose was 1.0 mg because of a case of endophthalmitis in the 2.0 mg cohort. Drug-related adverse events were reported by 13 (41%) of 32 patients; they included ocular inflammation in 11 patients (7 mild, 4 moderate in severity). Visual acuity scores were stable or improved compared with baseline for ≥4 weeks following injection; both retinal thickness and fluorescein angiography leakage decreased in a dose-dependent manner. Rescue therapy was administered to 20 (91%) of 22 patients who received 0.04-0.4 mg MP0112 compared with 4 of 10 (40%) patients who received 1.0 or 2.0 mg. Of patients in the higher-dose cohorts who did not require rescue treatment, 83% (5/6) maintained reductions in central retinal thickness through week 16.
  
  
  CONCLUSIONS
  A single injection of 1.0 or 2.0 mg MP0112 resulted in mean decreases in retinal thickness and leakage area despite ocular inflammation. Larger-scale studies are warranted to confirm these observations.
authors.affiliation: Department of Ophthalmology, Hôpital Intercommunal de Créteil, Créteil, France.
authors.forename: Eric H
authors.initials: EH
authors.lastname: Souied
authors.affiliation: Centre d'ophtalmologie Monticelli-Paradis, Marseille, France.
authors.forename: François
authors.initials: F
authors.lastname: Devin
authors.affiliation: Centre Ophtalmologique Rabelais, Lyon, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Mauget-Faÿsse
authors.affiliation: Eye Clinic of University Hospital Brno, Masaryk University Brno, Brno, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Kolář
authors.affiliation: Bern Photographic Reading Center, Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: Ute
authors.initials: U
authors.lastname: Wolf-Schnurrbusch
authors.affiliation: Department of Ophthalmology, Inselspital, Bern University Hospital, Bern, Switzerland.
authors.forename: Carsten
authors.initials: C
authors.lastname: Framme
authors.affiliation: Service d'Ophtalmologie des Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Université Louis-Pasteur, Strasbourg, France.
authors.forename: David
authors.initials: D
authors.lastname: Gaucher
authors.affiliation: Department of Ophthalmology, Hôpital Intercommunal de Créteil, Créteil, France.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Querques
authors.affiliation: Molecular Partners, Zurich-Schlieren, Switzerland.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Stumpp
authors.affiliation: Department of Ophthalmology, Inselspital, Bern University Hospital, Bern, Switzerland. Electronic address: Sebastian.Wolf@insel.ch.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wolf
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017089:Ankyrin Repeat; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D020714:Maximum Tolerated Dose; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics; D011485:Protein Binding; D014018:Tissue Distribution; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014792:Visual Acuity / Q000502:physiology; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000378:metabolism
chemical_list: C581258:MP0112; D010455:Peptides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A