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

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

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.

Study Overview

• Status: Completed
• Conditions: Hypercholesteremia
• Intervention / Treatment: Drug: SHR-1209; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • FuWai Hospital , Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1; A single subcutaneous injection of SHR-1209 dose 1 versus placebo	Drug: SHR-1209; Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous; Drug: Placebo; Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous
EXPERIMENTAL: Cohort 2; A single subcutaneous injection of SHR-1209 dose 2 versus placebo	Drug: SHR-1209; Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous; Drug: Placebo; Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous
EXPERIMENTAL: Cohort 3; A single subcutaneous injection of SHR-1209 dose 3 versus placebo	Drug: SHR-1209; Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous; Drug: Placebo; Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous
EXPERIMENTAL: Cohort 4; A single subcutaneous injection of SHR-1209 dose 4 versus placebo	Drug: SHR-1209; Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous; Drug: Placebo; Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 30, 2018
• Primary Completion (ACTUAL): May 28, 2019
• Study Completion (ACTUAL): May 28, 2019

Study Registration Dates

• First Submitted: August 6, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (ACTUAL): August 16, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: SHR-1209 Phase 1
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia
• Other Study ID Numbers: SHR-1209-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No