Phase 2 Study of HEC88473 Injection in Subjects With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This is a multicenter, randomized, parallel, placebo- and active comparator-controlled phase 2 trial to evaluate the efficacy, safety, pharmacokinetics and immunogenicity in subjects with T2DM. Patients treated with diet and exercise alone, or in combination with stable metformin monotherapy (≥1500 mg/day or maximum tolerated dose ≥1000 mg/ day.), will be enrolled. Approximately 225 participants will be randomized. The study includes four stages: screening period (up to 2 weeks), lead-in period (2 weeks), treatment period (12 weeks) and safety follow-up period (3 weeks after treatment).

Official Title
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A Phase 2, Multicenter, Randomised, Paralleled, Placebo-controlled (Double-blind) and Active Drug-controlled (Open) Study to Investigate Efficacy and Safety of HEC88473 Injection in Subjects With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: HEC88473, Placebo, Dulaglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients 18 to 75 years of age, inclusive. Have T2DM for at least 3 months before screening based on the disease diagnostic criteria (WHO 1999). Have an HbA1c value of ≥7.5% and ≤10.5%, fasting blood-glucose ≤13.9 mmoL/L, at screening and visit 3. Exclusion Criteria: Have type 1 diabetes mellitus. Have had ≥1 episode of severe hypoglycemia within 6 months before screening, or history of recurrent hypoglycemia (history of hypoglycemia more than 3 times in 3 months). Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (ALT) level >2.5 times the upper limit of the reference range at screening. Have a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2) at screening. Have serum calcitonin ≥20 ng/L at screening. Fasted triglycerides > 5.7 mmol/L at screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HEC88473 dose1<br>T2DM subjects, receiving a weekly dose of HEC88473 dose1 | Drug: HEC88473, Placebo, Dulaglutide<br>* T2DM subjects, receiving a weekly dose of HEC88473, placebo or dulaglutide.<br>|
| Experimental: HEC88473 dose2<br>T2DM subjects, receiving a weekly dose of HEC88473 dose2 | Drug: HEC88473, Placebo, Dulaglutide<br>* T2DM subjects, receiving a weekly dose of HEC88473, placebo or dulaglutide.<br>|
| Experimental: HEC88473 dose3<br>T2DM subjects, receiving a weekly dose of HEC88473 dose3 | Drug: HEC88473, Placebo, Dulaglutide<br>* T2DM subjects, receiving a weekly dose of HEC88473, placebo or dulaglutide.<br>|
| Placebo Comparator: Placebo<br>T2DM subjects, receiving a weekly dose of placebo | Drug: HEC88473, Placebo, Dulaglutide<br>* T2DM subjects, receiving a weekly dose of HEC88473, placebo or dulaglutide.<br>|
| Active Comparator: Dulaglutide<br>T2DM subjects, receiving a weekly dose of dulaglutide | Drug: HEC88473, Placebo, Dulaglutide<br>* T2DM subjects, receiving a weekly dose of HEC88473, placebo or dulaglutide.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of HbA1c at week 12 | HbA1c | Baseline to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline of weight at week 12 | weight | Baseline to week 12 | 
| Change from baseline of fasting blood-glucose at week 12 | fasting blood-glucose | Baseline to week 12 | 
| Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline to week 15 |