A phase ia dose-escalation study of the anti-factor D monoclonal antibody fragment FCFD4514S in patients with geographic atrophy

Diana V. Do, Dante J. Pieramici, Menno Van Lookeren Campagne, Tatiana Beres, Michel Friesenhahn, Yi Zhang, Erich C. Strauss

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)313-320
Number of pages8
JournalRetina
Volume34
Issue number2
DOIs
StatePublished - Feb 2014

Fingerprint

Geographic Atrophy
Complement Factor D
Immunoglobulin Fragments
Maximum Tolerated Dose
Monoclonal Antibodies
Visual Acuity
Serum
Safety
Antibodies, Monoclonal, Humanized
Intraocular Pressure
Antibody Formation
Half-Life
Pharmacokinetics
Antigens
Pharmaceutical Preparations
RHO(D) antibody

Keywords

  • Alternative complement pathway
  • AMD
  • Anti-factor D
  • FCFD4514S
  • Geographic atrophy

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Do, D. V., Pieramici, D. J., Van Lookeren Campagne, M., Beres, T., Friesenhahn, M., Zhang, Y., & Strauss, E. C. (2014). A phase ia dose-escalation study of the anti-factor D monoclonal antibody fragment FCFD4514S in patients with geographic atrophy. Retina, 34(2), 313-320. https://doi.org/10.1097/IAE.0b013e3182979ddd

A phase ia dose-escalation study of the anti-factor D monoclonal antibody fragment FCFD4514S in patients with geographic atrophy. / Do, Diana V.; Pieramici, Dante J.; Van Lookeren Campagne, Menno; Beres, Tatiana; Friesenhahn, Michel; Zhang, Yi; Strauss, Erich C.

In: Retina, Vol. 34, No. 2, 02.2014, p. 313-320.

Research output: Contribution to journalArticle

Do, DV, Pieramici, DJ, Van Lookeren Campagne, M, Beres, T, Friesenhahn, M, Zhang, Y & Strauss, EC 2014, 'A phase ia dose-escalation study of the anti-factor D monoclonal antibody fragment FCFD4514S in patients with geographic atrophy', Retina, vol. 34, no. 2, pp. 313-320. https://doi.org/10.1097/IAE.0b013e3182979ddd
Do, Diana V. ; Pieramici, Dante J. ; Van Lookeren Campagne, Menno ; Beres, Tatiana ; Friesenhahn, Michel ; Zhang, Yi ; Strauss, Erich C. / A phase ia dose-escalation study of the anti-factor D monoclonal antibody fragment FCFD4514S in patients with geographic atrophy. In: Retina. 2014 ; Vol. 34, No. 2. pp. 313-320.
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AU - Beres, Tatiana

AU - Friesenhahn, Michel

AU - Zhang, Yi

AU - Strauss, Erich C.

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N2 - 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.

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