945-P: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Cohort Study to Evaluate the Efficacy and Safety of 12 Once-Weekly Subcutaneous Doses of PB-119 to Patients with Type 2 Diabetes Mellitus as Monotherapy

Abstract

Background: PB119 (polyethylene glycol exenatide) which is a novel once-weekly subcutaneous GLP-1RA, has good pharmacokinetic properties. As a GLP-1RA, it shows a good safety profile and provides solid glycemic control while doesn’t need dose titration. We aimed to assess the efficacy and safety of PB119 monotherapy in Chinese patients with T2DM. Methods: In this phase 2 study, we randomly assigned 251 patients (1:1:1:1) to receive 3 doses of PB119 (75ug, 150ug, 200ug) or dose-matched placebo using permuted-block randomization, with a block size of 12 and without stratification. Eligible patients were men or women (aged 18-70 years) with T2DM who had a BMI of 18.5-35.0 kg/m², were on a diet and exercise regimen and untreated at least 3 months prior to screening. The study started with a 4-week placebo run-in period followed by a 12-week treatment period. The primary endpoint was the change in HbA1c from baseline to week 12, which was assessed in all patients who received at least 1 dose of study drug and had both baseline and at least 1 post-baseline HbA1c value. Safety was assessed in all patients who received at least 1 dose of study drug. ClinicalTrials.gov NCT03520972. Findings: At the end of week 12, the least squares mean change in HbA1c from baseline was -0.39% (95% CI -0.60 to -0.19) in the placebo group, -1.11% (-1.32 to -0.91) in the 75ug group, -1.57% (-1.78 to -1.37) in the 150ug group and -1.41% (-1.61 to -1.20) in the 200ug group. Compared with the placebo group, the change in HbA1c between baseline and week 12 was significant in all PB119 (p<0.001) groups. Significant reductions in TC and TG were observed in 150ug and 200ug groups (P<0.05), while the reductions in body weight and LDL-C were significant in 200ug group (P<0.05). There were no reports of drug-related serious adverse events or severe hypoglycemia. Disclosure M. Xu: None.