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出境医 / 临床实验 / The Safety, Tolerability and Efficacy of Multiple Subcutaneous Injections of SHR-1209 in Subjects With Hyperlipidemia

The Safety, Tolerability and Efficacy of Multiple Subcutaneous Injections of SHR-1209 in Subjects With Hyperlipidemia

Study Description
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

Condition or disease Intervention/treatment Phase
Hyperlipidemia Drug: SHR-1209 Drug: Placebo Phase 1 Phase 2

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : June 20, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : October 2020
Arms and Interventions
Arm Intervention/treatment
Experimental: SHR-1209
Participants received one of 6 dose levels of SHR-1209 administered as multiple subcutaneous doses.
Drug: SHR-1209

Pharmaceutical form: lyophilized formulation

Route of administration: subcutaneous


Placebo Comparator: Placebo
Participants received matching placebo dose regimens by subcutaneous injection.
Drug: Placebo

Pharmaceutical form: lyophilized formulation

Route of administration: subcutaneous


Outcome Measures
Primary Outcome Measures :
  1. Primary efficacy end point:Percent change from baseline to end of the dosing interval in LDL-C. [ Time Frame: Baseline to day 113 for group1,2,4,5 or day 169 for group 3,6 ]
  2. Primary safety end point:Number of subjects with adverse events. [ Time Frame: Baseline to day 169 for group 1,3,4,6 or day 141 for group 2,5 ]

Secondary Outcome Measures :
  1. Absolute change from baseline to end of the dosing interval in LDL-C. [ Time Frame: Baseline to day 113 for group1,2,4,5 or day 169 for group 3,6 ]
  2. Percent change from baseline to day 85 in LDL-C. [ Time Frame: Baseline to day 85 for all 6 groups ]
  3. Absolute change from baseline to day 85 in LDL-C. [ Time Frame: Baseline to day 85 for all 6 groups ]
  4. Percent change in PCSK9. [ Time Frame: Baseline to day 169 for group 1,3,4,6 or day 141 for group 2,5 ]
  5. Absolute change in PCSK9. [ Time Frame: Baseline to day 169 for group 1,3,4,6 or day 141 for group 2,5 ]

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Robert Zhu +86-02161623696 zhubo@hrglobe.cn

Locations
Layout table for location information
China, Guangdong
Sun Yat-Sen Memorial Hospital ,The Second Affiliated Hospital of Sun Yat-Sen University Recruiting
Guangzhou, Guangdong, China
Contact: li Yan         
Sponsors and Collaborators
Jiangsu HengRui Medicine Co., Ltd.
Tracking Information
First Submitted Date  ICMJE May 4, 2019
First Posted Date  ICMJE May 9, 2019
Last Update Posted Date August 12, 2019
Actual Study Start Date  ICMJE June 20, 2019
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2019)
  • Primary efficacy end point:Percent change from baseline to end of the dosing interval in LDL-C. [ Time Frame: Baseline to day 113 for group1,2,4,5 or day 169 for group 3,6 ]
  • Primary safety end point:Number of subjects with adverse events. [ Time Frame: Baseline to day 169 for group 1,3,4,6 or day 141 for group 2,5 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2019)
  • Absolute change from baseline to end of the dosing interval in LDL-C. [ Time Frame: Baseline to day 113 for group1,2,4,5 or day 169 for group 3,6 ]
  • Percent change from baseline to day 85 in LDL-C. [ Time Frame: Baseline to day 85 for all 6 groups ]
  • Absolute change from baseline to day 85 in LDL-C. [ Time Frame: Baseline to day 85 for all 6 groups ]
  • Percent change in PCSK9. [ Time Frame: Baseline to day 169 for group 1,3,4,6 or day 141 for group 2,5 ]
  • Absolute change in PCSK9. [ Time Frame: Baseline to day 169 for group 1,3,4,6 or day 141 for group 2,5 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Safety, Tolerability and Efficacy of Multiple Subcutaneous Injections of SHR-1209 in Subjects With Hyperlipidemia
Official Title  ICMJE 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
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hyperlipidemia
Intervention  ICMJE
  • Drug: SHR-1209

    Pharmaceutical form: lyophilized formulation

    Route of administration: subcutaneous

  • Drug: Placebo

    Pharmaceutical form: lyophilized formulation

    Route of administration: subcutaneous

Study Arms  ICMJE
  • Experimental: SHR-1209
    Participants received one of 6 dose levels of SHR-1209 administered as multiple subcutaneous doses.
    Intervention: Drug: SHR-1209
  • Placebo Comparator: Placebo
    Participants received matching placebo dose regimens by subcutaneous injection.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 8, 2019)
108
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03944109
Other Study ID Numbers  ICMJE SHR-1209-102
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jiangsu HengRui Medicine Co., Ltd.
Study Sponsor  ICMJE Jiangsu HengRui Medicine Co., Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Jiangsu HengRui Medicine Co., Ltd.
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP