Clinical trial NCT03944109: The Safety, Tolerability and Efficacy of Multiple Subcutaneous Injections of SHR-1209 in Subjects With Hyperlipidemia
Official title: The Safety, Tolerability and Efficacy of Multiple Subcutaneous Injections of SHR-1209 in Subjects With Hyperlipidemia - A PhaseⅠb/Ⅱ Randomized, Double-Blind, Placebo-Controlled Clinical Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hyperlipidemia
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-05-09
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, placebo- controlled phaseⅠb/Ⅱclinical study. Totally 108 subjects are planned to enrolled with 36 subjects in three low-dose groups (group 1, group 2 and group 3) and 72 subjects in three high-dose groups (group 4, group 5, and group 6).12 subjects with hyperlipidemia who received statin stable treatment for more than 28 days are enrolled in each low-dose group, randomly given SHR-1209 or placebo treatment at a ratio of 5:1. 24 subjects with hyperlipidemia who received statin stable treatment for more than 28 days are enrolled in each high-dose group, randomly given SHR-1209 or placebo treatment at a ratio of 5:1. The primary objective of this study is to evaluate the safety, tolerability, and efficacy of multiple subcutaneous injections of SHR-1209 in hyperlipidemia subjects treated with stabilized dose of statin. Groups detail as follows:

1. SHR-1209 dose 1 /placebo frequence 1
2. SHR-1209 dose 2 /placebo frequence 2
3. SHR-1209 dose 3 /placebo frequence 3
4. SHR-1209 dose 4 /placebo frequence 1
5. SHR-1209 dose 5 /placebo frequence 2
6. SHR-1209 dose 6 /placebo frequence 3


Eligibility criteria: Inclusion Criteria:

1. Age ≥18 and ≤65 years old;
2. Subjects who are receiving statin therapy at the time of screening or who are eligible for statin therapy can randomized to receive a stable dose of statin therapy for more than 28 days and are willing to maintain stable statin therapy in this study;
3. Low-density lipoprotein cholesterol (LDL-C) level ≥2.6mmol/L of subjects who receiving statin and/or other lipid-lowering therapy at the time of screening, or LDL-C≥ 3.4mmol/L of subjects who didn't receive any-lowering therapy at the time of screening, and LDL-C still ≥2.6mmol/L before randomization;
4. Fasting triglycerides ≤4.5 mmol/L;
5. Body mass index (BMI) ≥18 and ≤ 35 kg/m2;
6. Signed informed consent.

Exclusion Criteria:

1. 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;
2. Diagnosis of homozygous familial hypercholesterolemia;
3. New York heart association (NYHA) defined Ⅱ - Ⅳ history of heart failure;
4. History of acute coronary syndrome (e.g. myocardial infarction, hospitalization for unstable angina), or percutaneous coronary intervention, or coronary artery bypass graft, or history of cerebrovascular disease, within 12 months prior to screening;
5. Uncontrolled severe arrhythmias that are not controlled by drugs or other therapy within 12 months prior to enrollment;
6. Uncontrolled hypertension (systolic blood pressure ≥ 160 and/or diastolic blood pressure ≥ 100 mmHg);
7. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or gamma pancreatic acyl transferase (GGT), more than 2.5x ULN;
8. Subjects with previous malignant tumor diseases. etc.

Primary outcomes:
measure: Primary efficacy end point:Percent change from baseline to end of the dosing interval in LDL-C.
timeFrame: Baseline to day 113 for group1,2,4,5 or day 169 for group 3,6
measure: Primary safety end point:Number of subjects with adverse events.
timeFrame: Baseline to day 169 for group 1,3,4,6 or day 141 for group 2,5
Secondary outcomes:
measure: Absolute change from baseline to end of the dosing interval in LDL-C.
timeFrame: Baseline to day 113 for group1,2,4,5 or day 169 for group 3,6
measure: Percent change from baseline to day 85 in LDL-C.
timeFrame: Baseline to day 85 for all 6 groups
measure: Absolute change from baseline to day 85 in LDL-C.
timeFrame: Baseline to day 85 for all 6 groups
measure: Percent change in PCSK9.
timeFrame: Baseline to day 169 for group 1,3,4,6 or day 141 for group 2,5
measure: Absolute change in PCSK9.
timeFrame: Baseline to day 169 for group 1,3,4,6 or day 141 for group 2,5
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital ,The Second Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
Study officials:
References:
citation: Xu M, Zhu X, Wu J, Zhang Y, Zhao D, Wang X, Ding Y, Cao Y, Li C, Hu W, Sheng J, Luo Z, Zheng Z, Hu J, Liu J, Zhou X, Shen A, Ding X, Zhang Y, Zhao Y, Li Y, Zhong S, An S, Zou J, Yan L. PCSK9 inhibitor recaticimab for hypercholesterolemia on stable statin dose: a randomized, double-blind, placebo-controlled phase 1b/2 study. BMC Med. 2022 Jan 18;20(1):13. doi: 10.1186/s12916-021-02208-w.