The PK/PD Study of A Single Subcutaneous Injection of SHR-1209 in Healthy Subjects

Study Overview
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Brief Summary
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This is a Single Center, Randomized, Double-blind, Dose Escalation, Placebo Parallel Controlled PhaseⅠClinical study to Evaluate the Safety, Tolerability and Pharmacokinetics, Pharmacodynamics with A Single Subcutaneous Injection of SHR-1209 in Healthy Subjects. The primary objective of this study is to investigate the safety and tolerability of a range of subcutaneous SHR-1209 in healthy subjects. Secondary objectives are to determine the pharmacokinetics (PK) and pharmacodynamics(PD) profile of SHR-1209 in healthy subjects including assessment of immunogenicity.

Detailed Description
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32 adult healthy subjects with 4 dose groups will be enrolled in the study, including two subjects in the lowest dose group, all of whom received the SHR-1209 without placebo control. The other three groups have 10 subjects in each group, 8 administered SHR-1209 and 2 administered placebo. The primary endpoint is the Safety and Tolerability : adverse events, vital signs, physical examination, laboratory examination, 12 lead electrocardiogram, injection site reactions, etc.

Official Title
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Pharmacokinetics, Pharmacodynamics, Safety and Tolerability Study Following A Single Subcutaneous Injection of SHR-1209 in Healthy Subjects

Conditions
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Hypercholesteremia

Intervention / Treatment
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* Drug: SHR-1209
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 and ≤45 years old; The body mass index (BMI) should be 19 or greater and < 28kg/m2, the male weigh ≥50.0kg and <90.0kg, and the female weigh ≥45.0kg and <90.0kg; Serum LDL-C concentration≥2.0mmol/L and < 4.1mmol/L; Fasting triglycerides < 2.3 mmol/L; The comprehensive physical examination is eligible or slightly abnormal but the researchers determine no clinical implication. Signed informed consent. Exclusion Criteria: Subjects determined by the researchers have diseases that affect drug absorption, distribution, metabolism and excretion or low compliance; A clinical history of drug allergy or a history of atopic allergic diseases (asthma, urticaria, eczema dermatitis) or a known allergy to experimental or similar experimental drugs; Serum creatinine exceeded the upper limit of normal value (ULN) during screening; Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or gamma pancreatic acyl transferase (GGT), more than 2 x ULN, or total bilirubin more than 1.5 x ULN during screening; Human immunodeficiency virus antibody (HIV-ab), syphilis serological examination, hepatitis b virus surface antigen (HBsAg), hepatitis c virus antibody (HCV-ab) were positive; Subjects with previous malignant tumor diseases; 3 months prior to screening involved in any drug or medical device clinical subjects, or within 5 half-life of drugs (test drug half-life more than 3 months) before screening. etc

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>A single subcutaneous injection of SHR-1209 dose 1 versus placebo | Drug: SHR-1209<br>* Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous<br>Drug: Placebo<br>* Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous<br>|
| Experimental: Cohort 2<br>A single subcutaneous injection of SHR-1209 dose 2 versus placebo | Drug: SHR-1209<br>* Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous<br>Drug: Placebo<br>* Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous<br>|
| Experimental: Cohort 3<br>A single subcutaneous injection of SHR-1209 dose 3 versus placebo | Drug: SHR-1209<br>* Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous<br>Drug: Placebo<br>* Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous<br>|
| Experimental: Cohort 4<br>A single subcutaneous injection of SHR-1209 dose 4 versus placebo | Drug: SHR-1209<br>* Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous<br>Drug: Placebo<br>* Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events |  | Pre-dose to 150 days after dose administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of PK parameter-time to maximum concentration (Tmax) |  | Pre-dose to 150 days after dose administration | 
| Assessment of PK parameter-maximum concentration (Cmax) |  | Pre-dose to 150 days after dose administration | 
| Assessment of PK parameter-area under curve (AUC) |  | Pre-dose to 150 days after dose administration | 
| Assessment of PD parameter-change in Low-Density Lipoprotein Cholesterol (LDL-C) from baseline |  | Pre-dose to 150 days after dose administration | 
| Assessment of PD parameter-change in Total Cholesterol (T-C) from baseline |  | Pre-dose to 150 days after dose administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SHR-1209 Phase 1