ZGN-1061 is a second-generation methionine aminopeptidase 2 (MetAP2) inhibitor in development for treatment of T2D. This clinical trial evaluated ZGN-1061 (0.05, 0.3, 0.9, or 1.8 mg) vs. placebo (PBO) administered SC every 3 days for 12 weeks on change from baseline in A1C in individuals with T2D at multiple sites in Australia/New Zealand. Stable noninsulin diabetes therapy was permitted. Baseline (ITT population N=175): 52% female, 77% white, (mean±SD) age 54±8 y, A1C 8.6±1.1%, BMI 37±7 kg/m2, T2D duration 8±6 y. Interim analysis results (0.05, 0.3, 0.9 mg ZGN-1061) were presented previously. Here, we report additional results with 0.9 and 1.8 mg ZGN-1061. The LS mean±SE A1C change for PBO was 0.2±0.1% (N=42) vs. -0.4±0.1% (N=44) and -0.9±0.2% (N=23) for 0.9 and 1.8 mg ZGN-1061, respectively. The LS mean±SE difference vs. PBO was -0.6±0.2% and 1.1±0.2% for 0.9 mg (p=0.0003) and 1.8 mg (p<0.0001). The LS mean±SE weight change for PBO was -0.6±0.3 kg vs. -1.4±0.3 kg (p=ns) and -2.8±0.5 kg (p<0.001) for 0.9 and 1.8 mg ZGN-1061. Dose-dependent fasting and postprandial glucose reductions were observed for ZGN-1061 (p<0.05 vs. PBO); β-cell function and insulin sensitivity were improved with 1.8 mg ZGN-1061 (p<0.05 vs. PBO). ZGN-1061 also improved triglycerides, hsCRP, adiponectin, and leptin (p<0.05 vs. PBO). Across all ZGN-1061 treatment groups, adverse events (AEs) were primarily mild/moderate without any notable trends. The completion rate was 93% (163/175). Three subjects in ZGN-1061 groups withdrew due to AEs (sensory disturbance, 0.05 mg; upper abdominal pain, 0.9 mg; injection site urticaria, 1.8 mg). There were no reports of venous thrombosis or changes in thrombosis markers indicative of a thrombosis event. ZGN-1061 (1.8 mg) demonstrated statistically significant and clinically meaningful efficacy; the largest reductions in A1C and weight were observed at 12 weeks with no evidence of a waning effect and no notable safety signals.

Disclosure

T. Kim: Employee; Spouse/Partner; Celgene Corporation. Employee; Self; Zafgen, Inc. D. Zhuang: Employee; Self; Zafgen, Inc. T.L. Haugen: Employee; Self; Zafgen, Inc. D.D. Kim: Employee; Self; Zafgen, Inc. K. Taylor: Employee; Self; Zafgen, Inc.

© 2019 by the American Diabetes Association.
2019
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.