Treatment of Exudative Age-Related Macular Degeneration with a
Designed Ankyrin Repeat Protein that Binds Vascular Endothelial
Growth Factor: a Phase I/II Study

J 2014

Treatment of Exudative Age-Related Macular Degeneration with a Designed Ankyrin Repeat Protein that Binds Vascular Endothelial Growth Factor: a Phase I/II Study

SOUIED, Eric; Francois DEVIN; Martine MAUGET-FAYSSE; Petr KOLÁŘ; Ute WOLF-SCHNURRBUSCH et al.

Základní údaje

Originální název

Treatment of Exudative Age-Related Macular Degeneration with a Designed Ankyrin Repeat Protein that Binds Vascular Endothelial Growth Factor: a Phase I/II Study

Název česky

Léčba exsudativní věkem podmíněné degenerace designed ankyrin repeat proteinem, který váže vaskulární endoteliální růstový faktor: fáze I/II

Autoři

SOUIED, Eric; Francois DEVIN; Martine MAUGET-FAYSSE; Petr KOLÁŘ; Ute WOLF-SCHNURRBUSCH; Carsten FRAMME; David GAUCHER; Giuseppe QUERQUES; Michael STUMPP a Sebastian WOLF

Vydání

American journal of ophthalmology, New York, Elsevier Science Inc. 2014, 0002-9394

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

plné znění článku

Impakt faktor

Impact factor: 3.871

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/14:00078076

Organizační jednotka

Lékařská fakulta

Klíčová slova česky

Ranibizumab; Léčba; Darpiny Opora; Oko; Epidemiologie

Klíčová slova anglicky

Ranibizumab; Therapy; Darpins; Anchor; Eye; Epidemiology

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 21. 1. 2015 16:19, Soňa Böhmová

Anotace

V originále

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. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Přiložené soubory

PIIS0002939414003262.pdf

Citovat

SOUIED, Eric; Francois DEVIN; Martine MAUGET-FAYSSE; Petr KOLÁŘ; Ute WOLF-SCHNURRBUSCH; Carsten FRAMME; David GAUCHER; Giuseppe QUERQUES; Michael STUMPP a Sebastian WOLF. Treatment of Exudative Age-Related Macular Degeneration with a Designed Ankyrin Repeat Protein that Binds Vascular Endothelial Growth Factor: a Phase I/II Study. American journal of ophthalmology. New York: Elsevier Science Inc., 2014, roč. 158, č. 4, s. 724-732. ISSN 0002-9394. Dostupné z: https://doi.org/10.1016/j.ajo.2014.05.037.

@article{1215279,
   author = {Souied, Eric and Devin, Francois and MaugetandFaysse, Martine and Kolář, Petr and WolfandSchnurrbusch, Ute and Framme, Carsten and Gaucher, David and Querques, Giuseppe and Stumpp, Michael and Wolf, Sebastian},
   article_location = {New York},
   article_number = {4},
   doi = {https://doi.org/10.1016/j.ajo.2014.05.037},
   keywords = {Ranibizumab; Therapy; Darpins; Anchor; Eye; Epidemiology},
   language = {eng},
   issn = {0002-9394},
   journal = {American journal of ophthalmology},
   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},
   url = {http://dx.doi.org/10.1016/j.ajo.2014.05.037},
   volume = {158},
   year = {2014}
}

TY  - JOUR
ID  - 1215279
AU  - Souied, Eric - Devin, Francois - Mauget-Faysse, Martine - Kolář, Petr - Wolf-Schnurrbusch, Ute - Framme, Carsten - Gaucher, David - Querques, Giuseppe - Stumpp, Michael - Wolf, Sebastian
PY  - 2014
TI  - Treatment of Exudative Age-Related Macular Degeneration with a Designed Ankyrin Repeat Protein that Binds Vascular Endothelial Growth Factor: a Phase I/II Study
JF  - American journal of ophthalmology
VL  - 158
IS  - 4
SP  - 724-732
EP  - 724-732
PB  - Elsevier Science Inc.
SN  - 00029394
KW  - Ranibizumab
KW  - Therapy
KW  - Darpins
KW  - Anchor
KW  - Eye
KW  - Epidemiology
UR  - http://dx.doi.org/10.1016/j.ajo.2014.05.037
N2  - 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. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
ER  -

SOUIED, Eric; Francois DEVIN; Martine MAUGET-FAYSSE; Petr KOLÁŘ; Ute WOLF-SCHNURRBUSCH; Carsten FRAMME; David GAUCHER; Giuseppe QUERQUES; Michael STUMPP a Sebastian WOLF. Treatment of Exudative Age-Related Macular Degeneration with a Designed Ankyrin Repeat Protein that Binds Vascular Endothelial Growth Factor: a Phase I/II Study. \textit{American journal of ophthalmology}. New York: Elsevier Science Inc., 2014, roč.~158, č.~4, s.~724-732. ISSN~0002-9394. Dostupné z: https://doi.org/10.1016/j.ajo.2014.05.037.

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