Clinical trial NCT03634436: The PK/PD Study of A Single Subcutaneous Injection of SHR-1209 in Healthy Subjects
Official title: Pharmacokinetics, Pharmacodynamics, Safety and Tolerability Study Following A Single Subcutaneous Injection of SHR-1209 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypercholesteremia
Keywords: SHR-1209 Phase 1
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-08-16
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: Pre-dose to 150 days after dose administration
Secondary outcomes:
measure: Assessment of PK parameter-time to maximum concentration (Tmax)
timeFrame: Pre-dose to 150 days after dose administration
measure: Assessment of PK parameter-maximum concentration (Cmax)
timeFrame: Pre-dose to 150 days after dose administration
measure: Assessment of PK parameter-area under curve (AUC)
timeFrame: Pre-dose to 150 days after dose administration
measure: Assessment of PD parameter-change in Low-Density Lipoprotein Cholesterol (LDL-C) from baseline
timeFrame: Pre-dose to 150 days after dose administration
measure: Assessment of PD parameter-change in Total Cholesterol (T-C) from baseline
timeFrame: Pre-dose to 150 days after dose administration
Other outcomes:
Locations:
city: Beijing
country: China
facility: FuWai Hospital , Chinese Academy of Medical Sciences
state: Beijing
Study officials:
References: