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

Phase 1

Completed

• Conditions: Hypercholesteremia
• Interventions: Drug: SHR-1209; Drug: Placebo

• Registration Number: NCT03634436
• Lead Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2018-08-06
• Study First Submitted QC: 2018-08-14
• Study First Posted: 2018-08-16
• Study Start: 2018-08-30
• Primary Completion: 2019-05-28
• Study Completion: 2019-05-28
• Status Verified: 2019-09
• Last Update Submitted: 2022-08-02
• Last Update Posted: 2022-08-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

1. Age ≥18 and ≤45 years old;
2. 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;
3. Serum LDL-C concentration≥2.0mmol/L and < 4.1mmol/L;
4. Fasting triglycerides < 2.3 mmol/L;
5. The comprehensive physical examination is eligible or slightly abnormal but the researchers determine no clinical implication.
6. Signed informed consent.

Exclusion Criteria

1. Subjects determined by the researchers have diseases that affect drug absorption, distribution, metabolism and excretion or low compliance;
2. 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;
3. Serum creatinine exceeded the upper limit of normal value (ULN) during screening;
4. 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;
5. Human immunodeficiency virus antibody (HIV-ab), syphilis serological examination, hepatitis b virus surface antigen (HBsAg), hepatitis c virus antibody (HCV-ab) were positive;
6. Subjects with previous malignant tumor diseases;
7. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1	Placebo	A single subcutaneous injection of SHR-1209 dose 1 versus placebo
Cohort 3	Placebo	A single subcutaneous injection of SHR-1209 dose 3 versus placebo
Cohort 2	Placebo	A single subcutaneous injection of SHR-1209 dose 2 versus placebo
Cohort 3	SHR-1209	A single subcutaneous injection of SHR-1209 dose 3 versus placebo
Cohort 4	Placebo	A single subcutaneous injection of SHR-1209 dose 4 versus placebo
Cohort 2	SHR-1209	A single subcutaneous injection of SHR-1209 dose 2 versus placebo
Cohort 1	SHR-1209	A single subcutaneous injection of SHR-1209 dose 1 versus placebo
Cohort 4	SHR-1209	A single subcutaneous injection of SHR-1209 dose 4 versus placebo

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events	Pre-dose to 150 days after dose administration

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

FuWai Hospital , Chinese Academy of Medical Sciences; 🇨🇳 Beijing, Beijing, China