A First In Human Study to Assess CiVi007 in Subjects With an Elevated LDL-Cholesterol Level

Study Overview
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Brief Summary
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The primary objective of the study is to assess pharmacokinetics, dynamics, safety and tolerability of CiVi007 following single and multiple subcutaneous doses in subjects, including those on statin therapy

Official Title
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A Placebo-controlled, Single Blind, Randomised, Phase I, First In Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered CiVi007 in Subjects With an Elevated LDL C Level

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Drug: CiVi007
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Males or females, of any race, with fasting LDL C >2.6 mmol/L (100 mg/dL) and fasting serum triglycerides <4.52 mmol/L (400 mg/dL) haematology and clinical chemistry without clinically significant abnormal values Normal renal and hepatic function Women must not be pregnant, lactating or of child bearing potential Men must be willing to use appropriate contraception during the study Able to comprehend and willing to sign an ICF and to abide by the study restrictions. Key Exclusion Criteria: Any uncontrolled or serious disease, or any medical or surgical condition History or presence of coronary heart disease, peripheral artery disease, or cerebrovascular disease Uncontrolled hypertension Insulin dependent diabetes mellitus Secondary dyslipidemia History of renal or hepatic diseases, acquired immune deficiency syndrome, positive human immunodeficiency virus test and/or history of viral hepatitis B or C History of cancer within 5 years History of high alcohol consumption or positive alcohol breath test or urinary test for drugs of abuse Participation in another clinical study within 3 months prior to screening or participation in another study Use of treatment (e.g. antibody) towards PCSK9 History of multiple drug allergies or intolerance to subcutaneous injection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: Adaptive design allowing modifications in single and multidose arms
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A1<br>CiVi007 dose 1 | Drug: CiVi007<br>* cholesterol lowering drug<br>|
| Experimental: Cohort A2<br>CiVi007 dose 2 | Drug: CiVi007<br>* cholesterol lowering drug<br>|
| Experimental: Cohort A3<br>CiVi007 dose 3 | Drug: CiVi007<br>* cholesterol lowering drug<br>|
| Experimental: Cohort A4<br>CiVi007 dose 4 | Drug: CiVi007<br>* cholesterol lowering drug<br>|
| Experimental: Cohort A5<br>CiVi007 dose 5 | Drug: CiVi007<br>* cholesterol lowering drug<br>|
| Placebo Comparator: Combined placebo group<br>group response from placebo subsets of dosing cohorts | Other: Placebo<br>* matching placebo to CiVi007<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL Cholesterol | % LDL-C reduction | Maximum post dose within 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) of CiVi007 | Pharmacokinetic Outcome Measure | 8 weeks | 
| PCSK9 level | maximal % reduction in the level of circulating PCSK9 | Maximum post dose within 8 weeks |