Efficacy and Safety of SHR-1209 Combined With Lipid-lowering Agents in Patients With Hypercholesterolemia

• ClinicalTrials.gov Identifier: NCT04885218
• Recruitment Status: Completed
• First Posted: May 13, 2021
• Last Update Posted: January 31, 2024
• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Information provided by (Responsible Party): Jiangsu HengRui Medicine Co., Ltd.

Study Description

Brief Summary:

To evaluate the efficacy, safety, pharmacokinetics and immunogenicity of SHR-1209 subcutaneous administration in patients with non-familial hypercholesterolemia and mixed hyperlipidemia after lipid-lowering therapy

Condition or disease	Intervention/treatment	Phase
Non-familial Hypercholesterolemia; Mixed Hyperlipidemia	Drug: SHR-1209 ;placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 692 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: SHR-1209 combined with lipid-lowering agents
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicentre, Randomized, Double-blind, Placebo-controlled, Phase III Study to Evaluate the Efficacy and Safety of SHR-1209 Combined With Lipid-lowering Agents in the Stable Treatment of Patients With Non-familial Hypercholesterolemia and Mixed Hyperlipidemia .
• Actual Study Start Date: July 30, 2021
• Actual Primary Completion Date: May 23, 2023
• Actual Study Completion Date: May 23, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1：SHR-1209 / placebo	Drug: SHR-1209 ;placebo; SHR-1209 and placebo 150 mg subcutaneous injection once every 4 weeks for 48 weeks
Experimental: Cohort 2：SHR-1209 /placebo	Drug: SHR-1209 ;placebo; SHR-1209 and placebo 300 mg subcutaneous injection once every 8 weeks for 48 weeks
Experimental: Cohort 3：SHR-1209 / placebo	Drug: SHR-1209 ;placebo; SHR-1209 and placebo 450 mg subcutaneous injection once every 12 weeks for 48 weeks

Outcome Measures

Primary Outcome Measures :

1. Percentage change in LDL-C relative to baseline [ Time Frame: at 24 weeks of treatment ]

Secondary Outcome Measures :

1. The value of change in LDL-C relative to baseline [ Time Frame: at 24 weeks of treatment ]
2. Percentage change in LDL-C relative to baseline [ Time Frame: at 48 weeks of treatment; ]
3. The value of change in LDL-C relative to baseline , [ Time Frame: at 48 weeks of treatment; ]
4. Percentage change in non-HDL-C relative to baseline [ Time Frame: at 24 weeks of treatment; ]
5. Percentage change in non-HDL-C relative to baseline [ Time Frame: at 48 weeks of treatment; ]
6. Percentage change in ApoB relative to baseline [ Time Frame: at 24 weeks of treatment; ]
7. Percentage change in ApoB relative to baseline [ Time Frame: at 48 weeks of treatment; ]
8. Percentage change in TC/HDL-C relative to baseline [ Time Frame: at 24 weeks of treatment; ]
9. Percentage change in TC/HDL-C relative to baseline, [ Time Frame: at 48 weeks of treatment ]
10. Percentage change in ApoB/ApoA1 relative to baseline, [ Time Frame: at 24 weeks of treatment; ]
11. Percentage change in ApoB/ApoA1 relative to baseline, [ Time Frame: at 48 weeks of treatment; ]
12. Percentage change in LP (a) relative to baseline, [ Time Frame: at 24 weeks of treatment; ]
13. Percentage change in LP (a) relative to baseline, [ Time Frame: at 48 weeks of treatment; ]
14. Percentage change in TG relative to baseline [ Time Frame: at 24 weeks of treatment ]
15. Percentage change in TG relative to baseline [ Time Frame: at 48 weeks of treatment; ]
16. Percentage of patients who achieved LDL-C goal according to presence of ASCVD at baseline, [ Time Frame: at 48 weeks of treatment; ]
17. Percentage of patients who achieved LDL-C goal according to presence of ASCVD at baseline, [ Time Frame: at 48 weeks of treatment. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥18 and ≤80 on the date of signing the informed consent, male or female;
2. The report of LDL-C should be higher than the ideal lipid-lowering target according to ASCVD history;
3. Fasting triglycerides less than equal to 5.6 mmol/L；
4. Understand the study procedures and methods, volunteer to participate in the study, and sign the informed consent.

Exclusion Criteria:

1. Have the following diseases or treatment history : (1) Have known allergic reaction to experimental drugs, or have severe allergic reaction to other antibody drugs;(2) previous diagnosis of familial hypercholesterolemia according to Simon Broome Criteria;(3) cardiac function as defined by the New York Heart Association (NYHA) grade III-IV at screening or randomization or latest detected LVEF<30%;(4) CVD events within 3 months; (5) uncontrolled hypertension; (6) prior exposure to recaticimab or other PCSK9 inhibitors; (7) inadequate organ functions.
2. Any of the laboratory indicators met the following criteria at screening or at randomization :(1) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) exceeding 3 times the upper limit of normal (ULN), or total bilirubin exceeding 2 times the upper limit of normal (ULN);(2) Creatine kinase (CK) exceeds 3 times the upper limit of normal value (ULN);
3. General conditions :(1) the investigator judged that subcutaneous injection was not appropriate;(2) Fertile female subjects who did not use contraception within 4 weeks before screening; Or male or female subjects who do not agree to use high-efficiency contraceptives during the trial and for 24 weeks after the last dosing;(3) Women who are pregnant or lactating.
4. The Investigator determines that the subjects have poor compliance or have any factors that may prevent them from participating in the study, including, but not limited to, the study placing the subjects at unacceptable risk or possibly interfering with the study results.

Contacts and Locations

Locations

China, Beijing

Beijing Anzhen hospital

Beijing, Beijing, China, 100029

Sponsors and Collaborators

Jiangsu HengRui Medicine Co., Ltd.

More Information

• Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04885218
• Other Study ID Numbers: SHR-1209-302
• First Posted: May 13, 2021
• Last Update Posted: January 31, 2024
• Last Verified: January 2024

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hyperlipidemia, Familial Combined; Hyperlipoproteinemia Type V; Lipidoses; Hypercholesterolemia; Hyperlipidemias; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Hypertriglyceridemia