Arterial Inflammation, Cardiovascular Diseases
Conditions
Keywords
Phosphorylcholine human monoclonal antibody, Lipoprotein a
Brief summary
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).
Interventions
DRUGPC-mAb
Monthly treatment for 3 months (4 administrations)
DRUGPlacebo
Monthly treatment for 3 months (4 administrations)
Sponsors
Athera Biotechnologies AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Monocyte function | From baseline (Day 1) to visit 11 (Day 85) | Change in transendothelial migration (TEM) in monocytes isolated from treated subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Arterial stiffness | From baseline (Day 1) to visit 11 (Day 85) | Change in pulse wave velocity (PWV) (m/sec) |
| Adverse events (AEs)/serious AEs (SAEs) | From baseline (Day 1) to visit 11 (Day 85) | Incidence of AEs/SAEs |
| Vital signs, height | At screening (Day -63 to -1) | in cm |
| Vital signs, body weight | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | in kg |
| Vital signs, blood pressure | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | in mmHg |
| Vital signs, hear rate | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | in bpm |
| Arterial inflammation | From baseline (Day 1) to visit 11 (Day 85) | Change in tissue to background ratio (TBRmax) in common carotid arteries by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) |
| Physical examination including review of all organ systems | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | Any abnormalities will be recorded |
| Electrocardiogram (ECG), PR (PQ) | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | 12-lead ECG; PR (PQ) interval (in msec) will be measured and reported descriptively; any abnormalities will be recorded |
| ECG, QRS | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | 12-lead ECG; QRS interval (in msec) will be measured and reported descriptively; any abnormalities will be recorded |
| ECG, QT | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | 12-lead ECG; QT interval (in msec) will be measured and reported descriptively; any abnormalities will be recorded |
| ECG, QTcF | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | 12-lead ECG; QTcF interval (in msec) will be measured and reported descriptively; any abnormalities will be recorded |
| Vital signs, body temperature | At screening (Day -63 to -1), Day 1, Day 28, Day 56, Day 84 and end of study (Day 143) | in °C |
Countries
Netherlands, Sweden
Outcome results
None listed