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Am J Ophthalmol. 2014 Oct;158(4):724-732.e2. doi: 10.1016/j.ajo.2014.05.037. Epub 2014 Jun 5.

Treatment of exudative age-related macular degeneration with a designed ankyrin repeat protein that binds vascular endothelial growth factor: a phase I/II study.

Author information

1
Department of Ophthalmology, Hôpital Intercommunal de Créteil, Créteil, France.
2
Centre d'ophtalmologie Monticelli-Paradis, Marseille, France.
3
Centre Ophtalmologique Rabelais, Lyon, France.
4
Eye Clinic of University Hospital Brno, Masaryk University Brno, Brno, Czech Republic.
5
Bern Photographic Reading Center, Inselspital, Bern University Hospital, Bern, Switzerland.
6
Department of Ophthalmology, Inselspital, Bern University Hospital, Bern, Switzerland.
7
Service d'Ophtalmologie des Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Université Louis-Pasteur, Strasbourg, France.
8
Molecular Partners, Zurich-Schlieren, Switzerland.
9
Department of Ophthalmology, Inselspital, Bern University Hospital, Bern, Switzerland. Electronic address: Sebastian.Wolf@insel.ch.

Abstract

PURPOSE:

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).

DESIGN:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01086761.

PMID:
24907435
DOI:
10.1016/j.ajo.2014.05.037
[Indexed for MEDLINE]
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