Safety and Efficacy of CVI-LM001 in Patients With Hypercholesterolemia

Study Overview
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Brief Summary
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The purpose of this study is to determine if CVI-LM001 is effective and safe versus placebo in drug-naive subjects with elevated LDL cholesterol. There will be 4 groups receiving 100mg, 200mg, 300 mg and placebo treatment for 12 weeks respectively.

Detailed Description
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This study is a phase II study in subjects with elevated LDL cholesterol. As designed, the study will start with a 4-week, single-blind, placebo run-in period based on diet and exercise interventions for screening eligible subjects. After run-in, eligibility is confirmed with required laboratory tests at Day -1 prior to randomization. The eligible subjects are randomly assigned to CVI-LM001 100 mg, 200 mg, 300mg QD group or placebo QD group with ratio 1:1:1:1 to receive a 12-week double-blind treatment. After 12-week treatment, all investigational compound and placebo should be discontinued, followed by 4 week for safety evaluation.

Official Title
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A Randomized, Double-Blind, Parallel Group, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of CVI-LM001 in Patients With Hypercholesterolemia

Conditions
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Hyperlipidemia

Intervention / Treatment
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* Drug: 100 mg
* Drug: 200 mg
* Drug: 300 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 1. Aged 18-70 years, inclusive 2. Men and nonpregnant, nonlactating women 3. Hypercholesterolemic subjects with LDL-C level between 3.36mmol/L 4.88mmol/L at screening, inclusive Exclusion Criteria: 1. Fasting TG ≥3.99 mmol/L before randomization 2. History of significant cardiovascular , renal, pulmonary and liver diseases 3. History of diabetes 4. ALT or AST>1.5XULN at screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100 mg<br> | Drug: 100 mg<br>* One 100 mg pill and two placebo pills (QD) will be orally administered for 12 weeks<br>|
| Experimental: 200 mg<br> | Drug: 200 mg<br>* Two 100 mg pills and one placebo pill (QD) will be orally administered for 12 weeks<br>|
| Experimental: 300 mg<br> | Drug: 300 mg<br>* Three 100 mg pills (QD) will be orally administered for 12 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Three placebo pills (QD) will be orally administered for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C) | The percent change of LDL-C from baseline by comparing CVI-LM001 arms with placebo after 12 weeks of treatment | 12 weeks | 
| From Baseline to Week 12 in Number of Participants with Treatment-Emergent Adverse Events | Comparison treatment-emergent adverse events of LM001 arms with placebo arm after 12 weeks of treatment | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | The percent change of Non-HDL-C from baseline by comparing CVI-LM001 arms with placebo after 12 weeks of treatment | 12 weeks | 
| Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | The percent change of TC from baseline by comparing CVI-LM001 arms with placebo after 12 weeks of treatment | 12 weeks | 
| Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB) | The percent change of ApoB from baseline by comparing CVI-LM001 arms with placebo after 12 weeks of treatment | 12 weeks | 
| Percent Change From Baseline to Week 12 in Triglyceride (TG) | The percent change of TG from baseline by comparing CVI-LM001 arms with placebo after 12 weeks of treatment | 12 weeks | 
| Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) | The percent change of hsCRP from baseline by comparing CVI-LM001 arms with placebo after 12 weeks of treatment | 12 weeks | 
| Percent Change From Baseline to Week 12 in Lipoprotein（ a）(Lp(a)) | The percent change of Lp(a) from baseline by comparing CVI-LM001 arms with placebo after 12 weeks of treatment | 12 weeks | 
| Percent Change From Baseline to Week 12 in Proprotein Convertase Subtilisin/Kexin Type 9(PCSK9) | The percent change of PCSK9 from baseline by comparing CVI-LM001 arms with placebo after 12 weeks of treatment | 12 weeks | 
| Percent Change From Baseline to Week 12 in Apolipoprotein A1 (Apo A1) | The percent change of Apo A1 from baseline by comparing CVI-LM001 arms with placebo after 12 weeks of treatment | 12 weeks |