Arterial inflammation in subjects with elevated lipoprotein a (Lp[a]) MedDRA version: 20.0 Level: LLT Classification code 10051615 Term: Atherosclerotic cardiovascular disease System Organ Class: 100000022953
Conditions
Interventions
Product Name: 3G10
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: 3G10
Current Sponsor code: 3G10
Other descriptive name: 3G10
Concentration unit: mg/ml milligram(s)/millilitre
Concen
Sponsors
Athera Biotechnologies AB
Eligibility
Sex/Gender
All
Inclusion criteria
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 4. Weight of at least 63 kg and maximum 125 kg at screening (dose = 2-4 mg/kg body weight) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
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 Visit 3 and Visit 4 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 8. Ongoing treatment with statins or PCSK9 inhibitor Except when: • Statin is prescribed for primary prevention and Lp(a) >50 mg/dl and LDLc >100 mg/dL (2.5 mmol/L) • Statin and/or PCSK9, or other lipid lowering medication, are prescribed for secondary prevention, and Lp(a) >50 mg/dL 9. Systemic autoimmune diseases requiring treatment 10. Cancer, excluding basal cell carcinoma, within the last five years 11. Medical PET, SPECT, abdominal or thoracic CT examination during the previous 12 months’ time period 12. Conditions contraindicating MRI such as, but not limited to, claustrophobia, having a history of brain or heart surgery and pacemaker implantation, permanent make-up, past or present occupation as metalworker or welder. Having metallic implants that cannot be declared safe under the employed MRI scanning conditions, or which will significantly degrade MRI scan quality. 13. Positive HIV or hepatitis test 14. Clinically significant abnormal findings in haematology or clinical chemistry at screening or any value = 3 times the upper limit of normal haematology or clinical chemistry at screening 15. The subject is unable to understand the written and verbal instructions 16. Pregnant or breast feeding women. A negative urine pregnancy test must be demonstrated in females at screening. The females must be of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or post-menopausal defined as 12 month of amenorrhea (in questionable cases a blood sample with simultaneous determination of follicle stimulating hormone 25 150 IE/L and estradiol 450 mL during 3 months prior to screening 21. Subjects who have planned any scheduled invasive treatment/surgical procedure during the whole study 22. Investigator considers subject unlikely to comply with study procedures, restrictions and requirements 23. History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions, or severe allergic responses. 24. Recent (<1 month prior to screening) or current treatment with medications that may have a si
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the effects of four 250 mg 3G10 once monthly intravenous injections on monocyte function ex vivo. ;Secondary Objective: Primary objective The primary objective is to assess the effects of four 250 mg 3G10 once monthly intravenous injections on monocyte function ex vivo. Secondary objectives To assess functional effects of 3G10 on arterial inflammation in vivo To assess 3G10 effects on arterial stiffness To assess the safety and tolerability of 3G10 Exploratory objectives To assess the effects of 3G10 on heart function and LFR in a subgroup of the study population To study the pharmacodynamics of 3G10 by scavenger receptor and adhesion molecule expression on circulating monocytes and other circulating biomarkers To study the pharmacokinetics of 3G10 To further assess 3G10 effects on arterial stiffness over time To further assess functional effects of 3G10 on arterial inflammation in vivo To study the change in plasma protein patterns ;Primary end point(s): Change in TEM in monocytes isolated from treated subjects from baseline to visit 11;Timepoint(s) of evaluation of this end point: Baseline to visit 11 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints Change in 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 endpoints Safety and tolerability: AEs/SAEs, vital signs, physical examination, ECG and laboratory assessments including haematology, clinical chemistry and immunogenicity Exploratory endpoints Change from baseline in cardiac variables and LFR variables, as assessed by MRI, in a subgroup of the study population IgM anti-PC level, other circulating biomarkers, monocyte adhesion markers and scavenger receptors assessed by fluorescence-activated cell sorting (FACS) over time Pharmacokinetics: 3G10 serum levels Arterial stiffness variables, assessed by Sphygmocor Xcel TBRmean (carotid and aorta), TBRgluc (carotid and aorta) and TBRmax (aorta) assessed by 18F-FDG PET/CT Change in protein pattern from baseline to Visit 11 as assessed by proteomics measurements ;Timepoint(s) of evaluation of this end point: Secondary efficacy endpoints are evaluated from baseline to Visit 11 Safety endpoints: Adverse events (AE) will be assessed from administration of study drug until end of study visit. ECG will be assessed at screening and pre-dose as well as post dose at dosing visits. Vital signs and physical examination will be assessed during all visits to the clinic. Safety blood samples will be assessed at all visit to the clinic. Immunogenicity will be assessed pre-dose at each dosing visit dosing and at the end of study visit. Exploratory endpoints will be presented showing observed values and changes from baseline at each available visit/assessment | — |
Countries
Netherlands, Sweden
Contacts
Public ContactCEO
Athera Biotechnologies AB
Outcome results
None listed