1. The primary objective is to assess the effects of four 250 mg PC-mAB (also referred to as "3G10") once monthly intravenous injections on monocyte function ex vivo. The secondary objectives are to:1. assess the functional effects of 3G10…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Change in TEM in monocytes isolated from treated subjects from baseline to
visit 11
Secondary outcome
• Change in tissue to background ratio (TBRmax) in common carotid arteries by
fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG
PET/CT) from baseline to Visit 11
• Change in PWV (m/sec) assessed by Sphygmocor Xcel from baseline to Visit 11
• Safety and tolerability: number of AEs/SAEs, vital signs, physical
examination, ECG and Laboratory assessments including haematology, clinical
chemistry and immunogenicity.
Background summary
Inflammation and dyslipidaemia are key factors for the development and
progression of atherosclerosis and cardiovascular disease (CVD).
Atherosclerotic lesions are characterised by the presence of activated immune
cells, which produce pro-inflammatory cytokines, including interleukin-12
(IL-12), IL-18, interferon-gamma and tumour-necrosis factor (TNF) in the
lesions. Low density lipoprotein (LDL) plays a major role for these
inflammatory reactions in the arterial wall, accelerates the atherogenic
process and is a major determinant of plaque instability and increased
thrombogenicity. Another pro-inflammatory plasma lipoprotein is lipoprotein (a)
(Lp[a]), composed of apolipoprotein (a) bound to apolipoprotein B-100 of
LDL-like particles, where several studies show strong, independent and likely
causal relationship of increased plasma levels to risk of CVD. 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. There are currently no drugs available
on the market that are specifically tartgeting vascular inflammation, which is
the target of the compound used in this study.
Study objective
1. The primary objective is to assess the effects of four 250 mg PC-mAB (also
referred to as "3G10") once monthly intravenous injections on monocyte function
ex vivo.
The secondary objectives are to:
1. assess the functional effects of 3G10 on arterial inflammation in vivo
2. assess the effects of 3G10 on arterial stiffness
3. assess the safety and tolerability of 3G10
Study design
This is a Phase IIa, prospective, double-blind, randomised, placebo-controlled
multicentre study investigating the effects of treatment with PC-mAb (3G10)
for four monthly intravenous injections/infusions.
Intervention
Subjects will be allocated to receive either 250 mg 3G10 or matching placebo,
which are both referred to as IMP.
Each subject will receive monthly intravenous injections for four months.
Study burden and risks
Awaiting the outcome of the study, individual patients might not gain direct
"health" benefit from this study.
The results are expected to provide insight into the relation beween Lp(a) and
changes in the inflammatory activity in the atherosclerotic arteries. The
burden and the risk of participating in this study are estimated to be
intermediate. The study requires a maximum of 9 visits to the site and 4 phone
consultations. The exposure to radiation related to the PET/CT is 9.4 mSv for
the 2 PET/CT scans in this study. Maximum blooddraw in the study is below 450
ml (including clinical laboratory assesments.
Subjects should be in fasting state for 2 visits and should withhold from the
use of caffeine, alcohol, energydrinks and nicotine before PET/CT visit.
2 MRI examinations will be performed in a subgroup of the population
(optional).
PWV (PulseWaveVelocity) analysis will be performed 6x.
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Listed location countries
Age
Inclusion criteria
1. Provision of a signed written informed consent
2. Lp(a) above 50 mg/dL at screening
3. Male or female, >= 50 years of age at screening
Exclusion criteria
1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the result or the subject*s ability to participate in the study
2. Illness (including common colds) for the last 4 weeks before screening
3. Medical history of myocardial infarction (MI) or stroke within 12 months of screening
4. Ongoing or paroxysmal atrial fibrillation
5. Clinically overt heart failure
6. Hypertension defined as >=180/100 mmHg
7. Diabetes mellitus
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-002106-13-NL |
| CCMO | NL62199.018.17 |