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Ophthalmology. 2016 Aug;123(8):1722-1730. doi: 10.1016/j.ophtha.2016.04.025. Epub 2016 May 26.

Enhanced Benefit in Diabetic Macular Edema from AKB-9778 Tie2 Activation Combined with Vascular Endothelial Growth Factor Suppression.

Author information

1
Johns Hopkins, Wilmer Eye Institute, Baltimore, Maryland. Electronic address: pcampo@jhmi.edu.
2
Sierra Eye Associates, Reno, Nevada.
3
Medical Center Ophthalmology Associates, San Antonio, Texas.
4
Retina Research Institute of Texas, Abilene, Texas.
5
Retina Vitreous Associates Medical Group, Beverly Hills, California.
6
Retinal Consultants of Arizona, Phoenix, Arizona; USC Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California.
7
Johns Hopkins, Wilmer Eye Institute, Baltimore, Maryland.
8
Aerpio Therapeutics, Cincinnati, Ohio.

Abstract

PURPOSE:

To assess the effect of AKB-9778 alone or in combination with ranibizumab in subjects with diabetic macular edema (DME).

DESIGN:

A phase IIa, randomized, placebo- and sham injection-controlled, double-masked clinical trial.

PARTICIPANTS:

Subjects (n = 144) with decreased vision from DME and central subfield thickness (CST) ≥325 μm measured by spectral-domain optical coherence tomography (SD OCT) enrolled at 36 sites.

METHODS:

Subjects were randomized to (1) AKB-9778 monotherapy: subcutaneous AKB-9778 15 mg twice per day (BID) + monthly sham intraocular injections; (2) combination therapy: subcutaneous AKB-9778 15 mg BID + monthly 0.3 mg ranibizumab; or (3) ranibizumab monotherapy: subcutaneous placebo injections BID + monthly 0.3 mg ranibizumab. Best-corrected visual acuity (BCVA) and CST were measured at baseline and every 4 weeks.

MAIN OUTCOME MEASURES:

Primary outcome measure was mean change from baseline CST at week 12. Other outcomes included BCVA, safety assessments, and Diabetic Retinopathy Severity Score (DRSS).

RESULTS:

At week 12, mean change from baseline CST was significantly greater in the combination group (-164.4±24.2 μm) compared with the ranibizumab monotherapy group (-110.4±17.2 μm; P = 0.008) and was 6.2±13.0 μm in the AKB-9778 monotherapy group. Mean CST at week 12 and percentage of eyes with resolved edema was 340.0±11.2 μm and 29.2%, respectively, in the combination group versus 392.1±17.1 μm and 17.0%, respectively, in the ranibizumab monotherapy group. Mean change from baseline BCVA (letters) was 6.3±1.3 in the combination group, 5.7±1.2 in the ranibizumab monotherapy group, and 1.5±1.2 in the AKB-9778 monotherapy group. The percentage of study eyes that gained ≥10 or ≥15 letters was 8.7% and 4.3%, respectively, in the AKB-9778 monotherapy group, 29.8% and 17.0%, respectively, in the ranibizumab monotherapy group, and 35.4% and 20.8%, respectively, in the combination group. Improvements in DRSS in study eyes were similar across groups, and the percentage of qualified fellow eyes with a ≥2-step change was 11.4% in all AKB-9778-treated subjects compared with 4.2% in the ranibizumab monotherapy group. AKB-9778 was well tolerated, with no clear by-treatment differences in adverse events.

CONCLUSIONS:

Activation of Tie2 by subcutaneous injections of AKB-9778 combined with suppression of vascular endothelial growth factor (VEGF) causes a significantly greater reduction in DME than that seen with suppression of VEGF alone.

PMID:
27236272
DOI:
10.1016/j.ophtha.2016.04.025
[Indexed for MEDLINE]

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