A Study of PCSK9 Inhibitor AK102 in Healthy Subjects

Study Overview
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Brief Summary
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This is a first-in-human,randomized, double-blind, placebo-controlled, single dose escalation, phase 1 study to evaluate the safety, tolerability, PK/PD and immunogenicity of AK102 administered subcutaneously in healthy subjects. Subjects will be randomized into 4 planned single dose escalation cohorts or placebo cohort.

Official Title
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A First-in-Human,Randomized, Double-Blind, Placebo-Controlled, Single Dose Escalation,Phase 1 Study to Evaluate the Safety,Tolerability, Pharmacokinetics and Pharmacodynamics of AK102 in Healthy Subjects

Conditions
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Hypercholesterolaemia

Intervention / Treatment
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* Drug: AK102
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent. No clinically significant abnormalities judged by the principal investigator based on the medical history, physical examination, electrocardiogram and routine laboratory evaluations. Low-density lipoprotein cholesterol (LDL-C) level of 70-190 mg/dL (inclusive). Body mass index (BMI) ≥18 and ≤ 28 kg/m^2 , body weight >= 50 kg for male or >= 45 kg for female. Exclusion Criteria: Triglyceride concentration >400 mg/dL (4.5 mmol/L). History of hypersensitivity reactions to any substance of the investigation drug or other monoclonal antibodies. Drug or alcohol abuse within 6 months prior to dosing. Blood pressure >140 mmHg (systolic) or > 90 mmHg (diastolic)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK102 75mg<br>AK102 75mg | Drug: AK102<br>* AK102 single dose administered subcutaneously<br>|
| Experimental: AK102 150mg<br>AK102 150mg | Drug: AK102<br>* AK102 single dose administered subcutaneously<br>|
| Experimental: AK102 300mg<br>AK102 300mg | Drug: AK102<br>* AK102 single dose administered subcutaneously<br>|
| Experimental: AK102 500mg<br>AK102 500mg | Drug: AK102<br>* AK102 single dose administered subcutaneously<br>|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Placebo<br>* Placebo single dose administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent AE | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. | From single dose of AK102 through 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic characteristics of AK102 | Serum concentrations of AK102 at different timepoints before and after AK102 single dose. | over 12 weeks | 
| Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) | Low-Density Lipoprotein Cholesterol (LDL-C) blood concentrations before and after AK102 single dose. | At different time points from baseline through 12 weeks | 
| Percent Change From Baseline in PCSK9 | PCSK9 blood concentrations before and after AK102 single dose. | At different time points from baseline through 12 weeks | 
| Number of subjects who develop detectable anti-drug antibodies (ADAs) | The immunogenicity of AK102 will be assessed by summarizing the number of subjects who develop detectable ADAs. | At different time points from baseline through 12 weeks |