Phosphorylcholine PC-mAb Effects in Subjects With Elevated Lipoprotein a

Study Overview
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Brief Summary
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Inflammation and abnormal amount of lipids in the blood are key factors for the development and progression of atherosclerosis (thickening of the artery wall) and cardiovascular disease. Lipoprotein (a) is a pro-inflammatory plasma lipoprotein that is believed to be a risk factor for cardiovascular diseases. Vascular inflammation generates a range of effects, including endothelial dysfunction and migration of white blood cells into the vessel wall, which results in increased risk of cardiovascular events. This study is designed to assess the effects of multiple monthly intravenous infusions with the fully human antibody called PC-mAb, in subjects with elevated lipoprotein (a).

Official Title
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Double-blind, Randomised, Placebo-controlled, Multicentre, Phase IIa Study to Investigate the Effect of PC-mAb on Arterial Inflammation in Subjects With Elevated Lipoprotein a

Conditions
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Arterial Inflammation, Cardiovascular Diseases

Intervention / Treatment
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* Drug: PC-mAb
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Major inclusion criterion: Lp(a) above 50 mg/dL at screening Major exclusion criteria: Medical history of myocardial infarction (MI) or stroke within 12 months of screening Ongoing or paroxysmal atrial fibrillation Clinically overt heart failure Hypertension defined as ≥180/100 mmHg Diabetes mellitus Systemic autoimmune diseases requiring treatment Cancer, excluding basal cell carcinoma, within the last five years

Ages Eligible for Study
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Minimum Age: 50 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PC-mAb<br>Phosphorylcholine human monoclonal antibody, i.v. infusions | Drug: PC-mAb<br>* Monthly treatment for 3 months (4 administrations)<br>|
| Placebo Comparator: Placebo<br>Placebo to PC-mAb, i.v. infusions | Drug: Placebo<br>* Monthly treatment for 3 months (4 administrations)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monocyte function | Change in transendothelial migration (TEM) in monocytes isolated from treated subjects | From baseline (Day 1) to visit 11 (Day 85) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Arterial inflammation | Change in tissue to background ratio (TBRmax) in common carotid arteries by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) | From baseline (Day 1) to visit 11 (Day 85) | 
| Arterial stiffness | Change in pulse wave velocity (PWV) (m/sec) | From baseline (Day 1) to visit 11 (Day 85) | 
| Adverse events (AEs)/serious AEs (SAEs) | Incidence of AEs/SAEs | From baseline (Day 1) to visit 11 (Day 85) | 
| Vital signs, height | in cm | At screening (Day -63 to -1) | 
| Vital signs, body weight | in kg | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | 
| Vital signs, blood pressure | in mmHg | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | 
| Vital signs, hear rate | in bpm | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | 
| Vital signs, body temperature | in °C | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | 
| Physical examination including review of all organ systems | Any abnormalities will be recorded | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | 
| Electrocardiogram (ECG), PR (PQ) | 12-lead ECG; PR (PQ) interval (in msec) will be measured and reported descriptively; any abnormalities will be recorded | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | 
| ECG, QRS | 12-lead ECG; QRS interval (in msec) will be measured and reported descriptively; any abnormalities will be recorded | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | 
| ECG, QT | 12-lead ECG; QT interval (in msec) will be measured and reported descriptively; any abnormalities will be recorded | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | 
| ECG, QTcF | 12-lead ECG; QTcF interval (in msec) will be measured and reported descriptively; any abnormalities will be recorded | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phosphorylcholine human monoclonal antibody, Lipoprotein a