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A PHASE IA DOSE-ESCALATION STUDY OF THE ANTI-FACTOR D MONOCLONAL ANTIBODY FRAGMENT FCFD4514S IN PATIENTS WITH GEOGRAPHIC ATROPHY

Do, Diana V. MD*; Pieramici, Dante J. MD; van Lookeren Campagne, Menno PhD; Beres, Tatiana BS; Friesenhahn, Michel MA; Zhang, Yi PhD; Strauss, Erich C. MD; for the Phase Ia Investigators

doi: 10.1097/IAE.0b013e3182979ddd
Original Study

Purpose: 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.

Conclusion: 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.

At doses ranging from 0.1 mg to 10 mg in a single ascending dose Phase Ia study, intravitreal administration of a novel antigen-binding fragment from a humanized monoclonal antibody, FCFD4514S (anti-factor D), was considered to be safe and well tolerated in patients with geographic atrophy secondary to age-related macular degeneration.

*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.

Reprint requests: Diana V. Do, MD, Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198; e-mail: diana.do@unmc.edu

Investigators are listed online at http://journals.lww.com/retinajournal/pages/default.aspx.

D. V. Do has received research funding from Genentech, Inc. and Regeneron and served on an ISTA Pharmaceuticals advisory board. D. J. Pieramici is a consultant for Genentech, Inc, Alimera, and QLT and has received honoraria from Genentech, Inc. M. van Lookeren Campagne, T. Beres, M. Friesenhahn, Y. Zhang, and E. C. Strauss are employees of Genentech, Inc, with Roche stock/stock options.

Supported by Genentech, Inc. Support for third-party editorial assistance for this article, provided by Envision Scientific Solutions, was provided by Genentech, Inc.

© 2014 by Ophthalmic Communications Society, Inc.