A Study of HS-20094 in T2DM Participants

Study Overview
=================
Brief Summary
-----------------
This is a randomized, placebo and active-control, multiple-dose, phase IIa trial. Patients were randomly assigned to receive HS-20094 (12 patients), placebo (3 patients), or active control drug Semaglutide injection (3 patients) in a 4:1:1 ratio to each of four dose cohorts of 5 mg, 10 mg, 15 mg, and 20 mg. HS-20094 and placebo were administered in a double-blind design by subcutaneous injection once a week for a total of four times, and the dose was gradually increased weekly (2.5-2.5-5-5 mg, 5-510-10 mg, 5-10-15-15 mg, 5-10-15-20 mg). The active control drug semaglutide was administered by open-label, titrated subcutaneous injection once a week for a total of four times, and the dose was increased gradually every week until 1.0 mg (0.25-0.5-0.5-1.0 mg). The primary study objective was to 1) Evaluate the safety and tolerability of multiple subcutaneous injections of HS-20094 in subjects with type 2 diabetes mellitus (T2DM) with or without overweight or obesity;2) Evaluate the pharmacokinetics, pharmacodynamics and immunogenicity of multiple subcutaneous injections of HS-20094.

Official Title
-----------------
A Multiple-dose, Randomized, Double-blind, Placebo and Positive Controlled Phase IIa Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HS-20094 in Subjects With Type 2 Diabetes.

Conditions
-----------------
Type 2 Diabetes

Intervention / Treatment
-----------------
* Drug: HS-20094 5mg
* Drug: HS-20094 10mg
* Drug: HS-20094 15mg
* Drug: HS-20094 20mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects,20-65 years of age at the time of signing informed consent. Type 2 diabetes mellitus diagnosed for at least 3 months before the screening visit. Treated with conventional lifestyle intervention and stable treatment with metformin ( ≥ 1000 mg/day) at least 3 months prior to screening HbA1c 7.5-10%(both inclusive)at screening visit. Exclusion Criteria: A history of type 1 diabetes, specific diabetes, or secondary diabetes. Presence of-clinically significant lab or ECG results that may affect the evaluation of the efficacy or safety of the study drug at screening visit. Acute or chronic pancreatitis at any time before screening, or serum lipase/amylase above the upper limit of normal at screening. A history of grade 2 hypoglycemia(blood glucose 3.0 mmol/L)or grade 3 hypoglycemia(hypoglycemia with a serious event of consciousness and/or physical alteration requiring assistance from another person for recovery)within 6 months before screening. Diabetid ketoacidosis or hyperosmolar coma or lactic acidosis requiring hospitalization occurred within 6 months before screening. Severe infection such as diabetic foot infection, pneumonia, or sepsis within 30 days before screening. Uncontrollable hypertension. History of acute cardiovascular and cerebrovascular diseases within 6 months prior to screening. Any organ-system malignancies developed within 5 years except for cured local basal cell carcinoma of the skin and carcinoma in situ of the cervix. Pregnant or lactating woman. In the investigator's judgment, there were circumstances that affected subject safety or otherwise interfered with the evaluation of results.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HS-20094 5mg<br>Drug: HS-20094 Administrated by subcutaneous injection Drug: Placebo Administrated by subcutaneous injection Drug: Semaglutide Administrated by subcutaneous injection | Drug: HS-20094 5mg<br>* Administrated by subcutaneous injection<br>* Other names: HS-20094 injection 5mg;|
| Experimental: HS-20094 10mg<br>Drug: HS-20094 Administrated by subcutaneous injection Drug: Placebo Administrated by subcutaneous injection Drug: Semaglutide Administrated by subcutaneous injection | Drug: HS-20094 10mg<br>* Administrated by subcutaneous injection<br>* Other names: HS-20094 injection 10mg;|
| Experimental: HS-20094 15mg<br>Drug: HS-20094 Administrated by subcutaneous injection Drug: Placebo Administrated by subcutaneous injection Drug: Semaglutide Administrated by subcutaneous injection | Drug: HS-20094 15mg<br>* Administrated by subcutaneous injection<br>* Other names: HS-20094 injection 15mg;|
| Experimental: HS-20094 20mg<br>Drug: HS-20094 Administrated by subcutaneous injection Drug: Placebo Administrated by subcutaneous injection Drug: Semaglutide Administrated by subcutaneous injection | Drug: HS-20094 20mg<br>* Administrated by subcutaneous injection<br>* Other names: HS-20094 injection 20mg;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse event (AE), serious adverse event (SAE), AE leading to study discontinuation, AE severity and relation with study drug | A summary of AEs and SAEs, AE leading to study discontinuation, AE severity and relation with study drug will be reported in the reported adverse events module | From Baseline to Day 57. | 
| The number of participants with changes of laboratory tests blood routine, urine routine, blood biochemistry, coagulation function |  | From Baseline to Day 57 | 
| The changes ECG examination assessed by PR, R-R, QRS and QTcF | 12-lead electrocardiogram (ECG) parameters | From Baseline to Day 57 | 
| The changes in Blood pressure | Vital signs | From Baseline to Day 57 | 
| Pulse rate | Vital signs | From Baseline to Day 57 | 
| Respiratory rate | Vital signs | From Baseline to Day 57 | 
| Temperature | Vital signs | From Baseline to Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Cmax of HS-20094 | PK: Cmax of HS-20094 | Baseline to Day 57 | 
| Pharmacokinetics (PK): Tmax of HS-20094 | PK: Tmax of HS-20094 | Baseline to Day 57 | 
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of HS-20094 | PK: AUC of HS-20094 | Baseline to Day 57 | 
| Pharmacodynamics (PD): HbA1c | PD: change of HbA1c | Baseline to Day 29 |