Treatment of diabetic macular edema with a designed ankyrin repeat protein that binds vascular endothelial growth factor

A phase I/II study

Peter A Campochiaro, Roomasa Channa, Brian B. Berger, Jeffrey S. Heier, David M. Brown, Ulrike Fiedler, Julia Hepp, Michael T. Stumpp

Research output: Contribution to journalArticle

Abstract

Purpose: To evaluate the safety and bioactivity of MP0112, a designed ankyrin repeat protein (DARPin) that specifically binds vascular endothelial growth factor (VEGF) in patients with diabetic macular edema (DME). DARPins are a novel class of proteins selected for specific, high-affinity binding to a target protein. Design: Phase I/II, open-label, multicenter dose-escalation trial. Methods: After a single intravitreal injection of MP0112, the main outcomes were safety assessments, aqueous MP0112 levels, change in best-corrected visual acuity (BCVA), and foveal thickness measured by optical coherence tomography. Six cohorts were planned, but only 3 were enrolled (0.04, 0.15, 0.4 mg), because a maximally tolerated dose of 1.0 mg was identified in a parallel age-related macular degeneration trial. Results: Median aqueous concentration of MP0112 was 555 nM 1 week and >10 nM in 3 of 4 patients 12 weeks post injection of 0.4 mg. Median BCVA improvement at week 12 was 4, 6, and 10 letters in cohorts 1, 2, and 3. Ocular inflammation was observed in 11 patients (61%) and was severe in 1. High-resolution chromatography separated proinflammatory impurities from MP0112, resulting in a new formulation. Conclusions: A single intraocular injection of 0.4 mg MP0112 resulted in levels above the half-maximal inhibitory concentration and neutralization of VEGF in aqueous humor for 8-12 weeks. Despite inflammation in several patients, there was prolonged edema reduction and improvement in vision in several patients. The source of the inflammation was eliminated from a new preparation that is being tested in an ongoing clinical trial.

Original languageEnglish (US)
JournalAmerican Journal of Ophthalmology
Volume155
Issue number4
DOIs
StatePublished - Apr 2013

Fingerprint

Ankyrin Repeat
Macular Edema
Vascular Endothelial Growth Factor A
Proteins
Inflammation
Visual Acuity
Therapeutics
Intraocular Injections
Safety
Intravitreal Injections
Maximum Tolerated Dose
Aqueous Humor
Optical Coherence Tomography
Macular Degeneration
MP0112
Chromatography
Edema
Clinical Trials
Injections

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Treatment of diabetic macular edema with a designed ankyrin repeat protein that binds vascular endothelial growth factor : A phase I/II study. / Campochiaro, Peter A; Channa, Roomasa; Berger, Brian B.; Heier, Jeffrey S.; Brown, David M.; Fiedler, Ulrike; Hepp, Julia; Stumpp, Michael T.

In: American Journal of Ophthalmology, Vol. 155, No. 4, 04.2013.

Research output: Contribution to journalArticle

Campochiaro, Peter A ; Channa, Roomasa ; Berger, Brian B. ; Heier, Jeffrey S. ; Brown, David M. ; Fiedler, Ulrike ; Hepp, Julia ; Stumpp, Michael T. / Treatment of diabetic macular edema with a designed ankyrin repeat protein that binds vascular endothelial growth factor : A phase I/II study. In: American Journal of Ophthalmology. 2013 ; Vol. 155, No. 4.
@article{a0ec8d0c7e8a4401a37314e3c5b1cd47,
title = "Treatment of diabetic macular edema with a designed ankyrin repeat protein that binds vascular endothelial growth factor: A phase I/II study",
abstract = "Purpose: To evaluate the safety and bioactivity of MP0112, a designed ankyrin repeat protein (DARPin) that specifically binds vascular endothelial growth factor (VEGF) in patients with diabetic macular edema (DME). DARPins are a novel class of proteins selected for specific, high-affinity binding to a target protein. Design: Phase I/II, open-label, multicenter dose-escalation trial. Methods: After a single intravitreal injection of MP0112, the main outcomes were safety assessments, aqueous MP0112 levels, change in best-corrected visual acuity (BCVA), and foveal thickness measured by optical coherence tomography. Six cohorts were planned, but only 3 were enrolled (0.04, 0.15, 0.4 mg), because a maximally tolerated dose of 1.0 mg was identified in a parallel age-related macular degeneration trial. Results: Median aqueous concentration of MP0112 was 555 nM 1 week and >10 nM in 3 of 4 patients 12 weeks post injection of 0.4 mg. Median BCVA improvement at week 12 was 4, 6, and 10 letters in cohorts 1, 2, and 3. Ocular inflammation was observed in 11 patients (61{\%}) and was severe in 1. High-resolution chromatography separated proinflammatory impurities from MP0112, resulting in a new formulation. Conclusions: A single intraocular injection of 0.4 mg MP0112 resulted in levels above the half-maximal inhibitory concentration and neutralization of VEGF in aqueous humor for 8-12 weeks. Despite inflammation in several patients, there was prolonged edema reduction and improvement in vision in several patients. The source of the inflammation was eliminated from a new preparation that is being tested in an ongoing clinical trial.",
author = "Campochiaro, {Peter A} and Roomasa Channa and Berger, {Brian B.} and Heier, {Jeffrey S.} and Brown, {David M.} and Ulrike Fiedler and Julia Hepp and Stumpp, {Michael T.}",
year = "2013",
month = "4",
doi = "10.1016/j.ajo.2012.09.032",
language = "English (US)",
volume = "155",
journal = "American Journal of Ophthalmology",
issn = "0002-9394",
publisher = "Elsevier USA",
number = "4",

}

TY - JOUR

T1 - Treatment of diabetic macular edema with a designed ankyrin repeat protein that binds vascular endothelial growth factor

T2 - A phase I/II study

AU - Campochiaro, Peter A

AU - Channa, Roomasa

AU - Berger, Brian B.

AU - Heier, Jeffrey S.

AU - Brown, David M.

AU - Fiedler, Ulrike

AU - Hepp, Julia

AU - Stumpp, Michael T.

PY - 2013/4

Y1 - 2013/4

N2 - Purpose: To evaluate the safety and bioactivity of MP0112, a designed ankyrin repeat protein (DARPin) that specifically binds vascular endothelial growth factor (VEGF) in patients with diabetic macular edema (DME). DARPins are a novel class of proteins selected for specific, high-affinity binding to a target protein. Design: Phase I/II, open-label, multicenter dose-escalation trial. Methods: After a single intravitreal injection of MP0112, the main outcomes were safety assessments, aqueous MP0112 levels, change in best-corrected visual acuity (BCVA), and foveal thickness measured by optical coherence tomography. Six cohorts were planned, but only 3 were enrolled (0.04, 0.15, 0.4 mg), because a maximally tolerated dose of 1.0 mg was identified in a parallel age-related macular degeneration trial. Results: Median aqueous concentration of MP0112 was 555 nM 1 week and >10 nM in 3 of 4 patients 12 weeks post injection of 0.4 mg. Median BCVA improvement at week 12 was 4, 6, and 10 letters in cohorts 1, 2, and 3. Ocular inflammation was observed in 11 patients (61%) and was severe in 1. High-resolution chromatography separated proinflammatory impurities from MP0112, resulting in a new formulation. Conclusions: A single intraocular injection of 0.4 mg MP0112 resulted in levels above the half-maximal inhibitory concentration and neutralization of VEGF in aqueous humor for 8-12 weeks. Despite inflammation in several patients, there was prolonged edema reduction and improvement in vision in several patients. The source of the inflammation was eliminated from a new preparation that is being tested in an ongoing clinical trial.

AB - Purpose: To evaluate the safety and bioactivity of MP0112, a designed ankyrin repeat protein (DARPin) that specifically binds vascular endothelial growth factor (VEGF) in patients with diabetic macular edema (DME). DARPins are a novel class of proteins selected for specific, high-affinity binding to a target protein. Design: Phase I/II, open-label, multicenter dose-escalation trial. Methods: After a single intravitreal injection of MP0112, the main outcomes were safety assessments, aqueous MP0112 levels, change in best-corrected visual acuity (BCVA), and foveal thickness measured by optical coherence tomography. Six cohorts were planned, but only 3 were enrolled (0.04, 0.15, 0.4 mg), because a maximally tolerated dose of 1.0 mg was identified in a parallel age-related macular degeneration trial. Results: Median aqueous concentration of MP0112 was 555 nM 1 week and >10 nM in 3 of 4 patients 12 weeks post injection of 0.4 mg. Median BCVA improvement at week 12 was 4, 6, and 10 letters in cohorts 1, 2, and 3. Ocular inflammation was observed in 11 patients (61%) and was severe in 1. High-resolution chromatography separated proinflammatory impurities from MP0112, resulting in a new formulation. Conclusions: A single intraocular injection of 0.4 mg MP0112 resulted in levels above the half-maximal inhibitory concentration and neutralization of VEGF in aqueous humor for 8-12 weeks. Despite inflammation in several patients, there was prolonged edema reduction and improvement in vision in several patients. The source of the inflammation was eliminated from a new preparation that is being tested in an ongoing clinical trial.

UR - http://www.scopus.com/inward/record.url?scp=84875242688&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875242688&partnerID=8YFLogxK

U2 - 10.1016/j.ajo.2012.09.032

DO - 10.1016/j.ajo.2012.09.032

M3 - Article

VL - 155

JO - American Journal of Ophthalmology

JF - American Journal of Ophthalmology

SN - 0002-9394

IS - 4

ER -