The Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of HEC88473 in Healthy Subjects

Study Overview
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Brief Summary
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A Phase 1, double blind, placebo controlled, single and multiple ascending dose, safety, tolerability, pharmacokinetic, and pharmacodynamic study of HEC88473 in healthy subjects

Detailed Description
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This is the first time HEC88473 will be administered to humans. The aim of this study is to obtain safety, tolerability, PK, PD, and immunogenicity data of HEC88473 SC administration as single and multiple ascending doses in healthy subjects.

Official Title
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A Phase 1, Double Blind, Placebo Controlled, Single and Multiple Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of HEC88473 in Healthy Subjects

Conditions
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Non-alcoholic Steatohepatitis

Intervention / Treatment
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* Drug: HEC88473 injection
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, of any race, between 18 and 60 years of age, inclusive, at screening. Body weight ≥ 50 kg, and body mass index between 18.0 and 40.0 kg/m2, inclusive, at screening. In good health, determined by no clinically significant findings from medical history, physical examination, 12 lead ECG, vital signs measurements, and clinical laboratory evaluations at screening as assessed by the investigator (or designee). Able to comprehend and willing to sign an ICF and to abide by the study restrictions. Exclusion Criteria: Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee). History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator (or designee). History of alcoholism or drug/chemical abuse within 2 years prior to the first dosing. Alcohol consumption of > 21 units per week for males and > 14 units per week for females. One unit of alcohol equals 12 oz (360 mL) beer, 1½ oz (45 mL) liquor, or 5 oz (150 mL) wine. Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at screening and/or check-in. Immunization with a live attenuated vaccine or coronavirus vaccination within 1 month prior to the first dosing or planned vaccination during the course of the study. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half-lives (if known), whichever is longer, prior to the first dosing. Use or intend to use any prescription medications/products other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives within 14 days prior to first dosing, unless deemed acceptable by the investigator (or designee).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose of 0.5 mg HEC88473<br>Healthy subjects, receiving a single dose of 0.5 mg HEC88473 (N=6) or placebo(N=2) after meal. | Drug: HEC88473 injection<br>* HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection in the abdomen<br>|
| Experimental: Single dose of 1.7 mg HEC88473<br>Healthy subjects, receiving a single dose of 1.7 mg HEC88473 (N=6) or placebo(N=2) after meal. | Drug: HEC88473 injection<br>* HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection in the abdomen<br>|
| Experimental: Single dose of 5.1 mg HEC88473<br>Healthy subjects, receiving a single dose of 5.1 mg HEC88473 (N=6) or placebo(N=2) after meal. | Drug: HEC88473 injection<br>* HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection in the abdomen<br>|
| Experimental: Single dose of 10.2 mg HEC88473<br>Healthy subjects, receiving a single dose of 10.2 mg HEC88473 (N=6) or placebo(N=2) after meal. | Drug: HEC88473 injection<br>* HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection in the abdomen<br>|
| Experimental: Single dose of 17.0 mg HEC88473<br>Healthy subjects, receiving a single dose of 17.0 mg HEC88473 (N=6) or placebo(N=2) after meal. | Drug: HEC88473 injection<br>* HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection in the abdomen<br>|
| Experimental: Single dose of 25.5 mg HEC88473<br>Healthy subjects, receiving a single dose of 25.5 mg HEC88473 (N=6) or placebo(N=2) after meal. | Drug: HEC88473 injection<br>* HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection in the abdomen<br>|
| Experimental: Single dose of 34.0 mg HEC88473<br>Healthy subjects, receiving a single dose of 34.0 mg HEC88473 (N=6) or placebo(N=2) after meal. | Drug: HEC88473 injection<br>* HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection in the abdomen<br>|
| Experimental: Single dose of 44.2 mg HEC88473<br>Healthy subjects, receiving a single dose of 44.2 mg HEC88473 (N=6) or placebo(N=2) after meal. | Drug: HEC88473 injection<br>* HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection in the abdomen<br>|
| Experimental: Multiple doses of 1.7 mg HEC88473<br>Healthy subjects, receiving a weekly dose of 1.7 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. | Drug: HEC88473 injection<br>* HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection in the abdomen<br>|
| Experimental: Multiple doses of 5.1 mg HEC88473<br>Healthy subjects, receiving a weekly dose of 5.1 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. | Drug: HEC88473 injection<br>* HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection in the abdomen<br>|
| Experimental: Multiple doses of 10.2 mg HEC88473<br>Healthy subjects, receiving a weekly dose of 10.2 mg HEC88473 (N=10) or placebo (N=2) for 5 consecutive weeks after meal. | Drug: HEC88473 injection<br>* HEC88473 will be provided as a 17 mg/mL solution and will be administered by subcutaneous injection in the abdomen<br>Drug: Placebo<br>* Placebo will be administered by subcutaneous injection in the abdomen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) after a single dose of HEC88473 |  | Baseline to day 15 | 
| Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) after multiple dose of HEC88473 |  | Baseline to day 43 | 
| Cmax | Maximum observed plasma concentration of HEC88473 | Predose and postdose 4, 8, 10, 12, 14, 24, 48, 72, 96, 168, 216, and 336 hours | 
| AUC | Area under the plasma concentration-time curve (AUC) | Predose and postdose 4, 8, 10, 12, 14, 24, 48, 72, 96, 168, 216, and 336 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OGTT | Oral glucose tolerance test | Predose and postdose 2, 4 hours | 
| Assessment of the incidence of anti drug antibodies (ADA) developed against HEC88473 after dosing |  | Baseline to day 43 |