Results of an Interim Analysis of a Phase 2, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of ZGN-1061 in Patients with Obesity and Type 2 Diabetes

Abstract

ZGN-1061 (1061) is a methionine aminopeptidase 2 (MetAP2) inhibitor being developed to improve glycemic control in type 2 diabetes. This clinical trial investigated the effect of 12 weeks of subcutaneous (SC) 1061 (0.05, 0.3, 0.9 mg or placebo) administered every 3 days on A1C, safety, and tolerability. Stable noninsulin diabetes therapy was permitted. The study included 129 patients; an interim analysis was conducted on a subset of patients at week 8. Baseline characteristics of the interim ITT population (N=57): 54% male, 77% white, (mean±SD) age 54±8 years, A1C 8.7±1.0%, BMI 37.2±6.4 kg/m2. At week 8, the LS mean±SE change in A1C for placebo was 0.2±0.1% (N=13) vs. -0.4±0.2% with 0.9 mg 1061 (N=13, LS mean±SE difference -0.6±0.2%, p<0.02). In patients with week 12 measurements, the change in A1C was 0.4±0.2 (N=12) vs. -0.5±0.2 (N=8, difference -0.9±0.3, p<0.01). There were trends for weight loss and improved fasting plasma glucose with 0.9 mg 1061 vs. placebo as well as improvements in biomarkers, including hsCRP (week 8 -2.1±2.2 mg/L vs. 1.0±2.1, ns), adiponectin (1.0±0.3 ug/mL vs. -0.1±0.3, p<0.05), leptin (-6.9±1.9 ng/mL vs. 2.1±1.7, p<0.05), FGF-21 (0.026±0.014 ng/mL vs. 0.000±0.013; ns), and postprandial glucose AUC (p<0.01). Improvements in efficacy measures with the lower doses of 1061 were variable. There were no serious or severe adverse events (AEs) and no subjects withdrew due to an AE. The most common AE (1061>placebo) was upper respiratory tract infection. The 1061 pharmacokinetic profile indicated that exposure was within target levels for efficacy and safety and there were no changes in thrombosis markers (e.g., D-dimer). In this interim analysis, 1061 produced improvements in glycemic control and metabolic biomarkers consistent with MetAP2 inhibition. 1061 was also well tolerated with no safety signals in all doses tested. Week 12 results from the full analysis dataset will be presented. Disclosure T. Kim: Employee; Self; Zafgen. D. Zhuang: Employee; Self; Zafgen. T.E. Hughes: Board Member; Self; Zafgen. Employee; Self; Zafgen. Stock/Shareholder; Self; Zafgen. D.D. Kim: Employee; Self; Zafgen. K. Taylor: Employee; Self; Zafgen.