Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Subcutaneous Injections of HRS9531 in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The main purpose of this study is to assess the safety and tolerability of multiple subcutaneous injections of HRS9531 in patients with type 2 diabetes mellitus who have suboptimal glycaemic control after conventional lifestyle or metformin intervention.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo- and Positive-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Subcutaneous Injections of HRS9531 in Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: HRS9531
* Drug: Placebo
* Drug: Dulaglutide Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and infertility females, 18-65 years of age, inclusive, on the date of signing informed consent. Diagnosed with type 2 diabetes mellitus (T2DM) for at least 6 months. Treated with conventional lifestyle intervention alone or stable treatment with metformin (≥1000 mg/day) at least 8 weeks prior to screening. 7.0% ≤ HbA1c ≤10.5% at screening. Exclusion Criteria: History or presence of vital organ primary diseases, including but not limited to neuropsychiatric, cardiovascular, digestive, respiratory, urinary, endocrine, blood, immune and other diseases, judged by researchers to be unsuitable for this study. Diagnosed or suspected with type 1 diabetes mellitus, special types of diabetes or secondary diabetes. Have a history of acute complications of diabetes (diabetic ketoacidosis, lactic acidosis, hyperglycaemic hyperosmolar state, etc.) or episode of severe hypoglycaemic events within 12 months prior to screening. Have a presence of proliferative diabetic retinopathy, diabetic macular edema, or nonproliferative diabetic retinopathy requiring treatment during the trial; Participants in clinical trials of any drug or medical device in the 3 months prior to screening. Breast-feeding women. The investigator considers that the subject has any other factors that would make it inappropriate to participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Interventional Model Description: HRS9531 injection compared with placebo and open positive-controlled group
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Participants receive low dose level of HRS9531 or matched placebo administrated by multiple subcutaneous injection | Drug: HRS9531<br>* Administrated SC<br>Drug: Placebo<br>* Administrated SC<br>|
| Experimental: Group B<br>Participants receive medium dose level of HRS9531 or matched placebo administrated by multiple subcutaneous injection | Drug: HRS9531<br>* Administrated SC<br>Drug: Placebo<br>* Administrated SC<br>|
| Experimental: Group C<br>Participants receive high dose level of HRS9531 or matched placebo administrated by multiple subcutaneous injection | Drug: HRS9531<br>* Administrated SC<br>Drug: Placebo<br>* Administrated SC<br>|
| Active Comparator: Group D<br>Participants receive Dulaglutide 1.5 mg by multiple subcutaneous injection | Drug: Dulaglutide Injection<br>* Administrated SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (Safety and Tolerability) | A summary of adverse events, including serious adverse events (SAEs) and Hypoglycemic Events | Screening period up to Day 62 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration Versus Time Curve (AUC) of HRS9531 |  | Start of Treatment up to Day 62 | 
| Maximum Concentration (Cmax) of HRS9531 |  | Start of Treatment up to Day 62 | 
| Change from Baseline in Fasting Blood Glucose (FBG) |  | Baseline up to Day 62 | 
| Change from Baseline in Hemoglobin A1c (HbA1c) |  | Baseline up to Day 29 | 
| Change from Baseline in Weight |  | Baseline up to Day 62 | 
| Immunogenicity: anti-HRS9531 antibody |  | Start of Treatment up to Day 62 |