Overview

This study is a multicenter, randomized, double-blind (with open-label dose levels and active comparator), parallel-group, placebo- and active-controlled Phase 2 clinical trial aimed at evaluating the efficacy, safety, immunogenicity, and pharmacokinetic (PK) characteristics of HDM1005 in subjects with Type 2 Diabetes Mellitus (T2DM) who have inadequate glycemic control after diet/exercise or metformin therapy.

A total of 216 subjects will be enrolled. All subjects will be stratified by baseline HbA1c levels (≤8.5% or >8.5%) and prior metformin use, then randomized 1:1:1:1:1:1 to: Group 1 (HDM1005 0.5 mg), Group 2 (HDM1005 1.0 mg), Group 3 (HDM1005 2.0 mg), Group 4 (HDM1005 3.0 mg), Group 5 (Placebo), and Group 6 (open-lable dulaglutide 1.5 mg, active comparator), with 36 subjects in each treatment group. Within each dose cohort (0.5/1.0/2.0/3.0mg), there will be ~45 total subjects (36 HDM1005 + 9 placebo). The 1.0mg, 2.0mg, and 3.0mg cohorts will implement dose titration.

The study consists of: 2-week screening, 20-week treatment, and 4-week safety follow-up. The end-of-study visit will be conducted 28 days after the last administration cycle.

Eligibility

Inclusion Criteria:

• Confirmed as Type 2 Diabetes Mellitus (T2DM) for at least 24 weeks;
• Hemoglobin A1c (HbA1c) ≥7.5% and ≤10.5%
• Body Mass Index (BMI within the range of 22.5 ~ 40.0 kg/m2

Exclusion Criteria:

• Other types of diabetes besides T2DM
• Acute complications of diabetes (such as diabetic ketoacidosis, diabetic lactic acidosis, or hyperosmolar non-ketotic coma) occurred within 24 weeks prior to signing the Informed Consent Form (ICF)
• History of a level 3 hypoglycemic episode or a history of asymptomatic hyp oglycemic episodes within 24 weeks prior to signing the ICF
• History or family history of medullary thyroid carcinoma (MTC), thyroid C-cell hyperplasia, or multiple endocrine neoplasia type 2 (MEN2)
• History of acute or chronic pancreatitis; or presence of risk factors for pancreatitis; or history of symptomatic gallbladder disease within 24 weeks prior to signing the ICF
• Investigator determines that the subject has a condition or disease affecting gastric emptying or gastrointestinal nutrient absorption, such as weight-loss surgery or other gastric resections, irritable bowel syndrome, dyspepsia, or gastroparesis
• Use of antidiabetic medications within 12 weeks prior to signing the ICF
• Hemoglobin (Hb) <100 g/L (female) or <110 g/L (male)
• FPG ≥13.9 mmol/L
• Aspartate aminotransferase (AST) >2.5× upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >2.5× ULN
• Total bilirubin >1.5× ULN
• Fasting triglyceride (TG) >5.6 mmol/L (500 mg/dL)