GENETICALLY DEFINED FAMILIAL PRIMARY HYPOALPHALIPOPROTEINEMIA (FPHA mutation in ApoA1 and/or ABCA1 gene) MedDRA version: 19.1 Level: LLT Classification code 10019185 Term: HDL cholesterol decreased System Organ Class: 100000004848
Conditions
Sponsors
CERENIS THERAPEUTICS SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients, aged 18 and above. 2. Female patients who are not either surgically sterile (e.g., tubal ligation or removal of ovaries or uterus) or post-menopausal (no spontaneous menstrual periods for at least one year) must agree to use one of the following forms of contraception from screening until 90 days after the completion of the study medication: (1) systemic hormonal treatment (2) an IUD which was implanted at least 2 months prior to screening or (3) "double-barrier" contraception (condom, diaphragm and spermicide are each considered a barrier), or (4) agree to remain sexually abstinent during the entire study period (when contraception is not acceptable for cultural or religious beliefs) 3. Sign written informed consent after the scope and nature of the investigation have been explained to them before screening evaluations and willing to comply with the study restrictions 4. Are fluent in the language of the investigator, study staff (including raters), and the informed consent 5. Diagnosis of genetically confirmed HDL-c deficiency due to defects in genes coding for e.g. ABCA1 and/or ApoA-1 6. IF the subject is on lipid-lowering therapy or NEEDS to be treated with lipid-lowering therapy then the subject must be on a stable dose at least 6 weeks prior to the baseline procedures. 7. Background symptomatic or asymptomatic cardiovascular disease should be present as such: - For symptomatic cardiovascular disease: i) history of cardio or cerebrovascular events, ii) diagnosed coronary artery disease (CAD), iii) diagnosed carotid or peripheral stenosis, iv) previous myocardial revascularisation - percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG). - For asymptomatic cardiovascular disease: patients with subclinical atherosclerosis diagnosed using imaging method such as i)vDoppler ultrasound, ii)vB-mode ultrasonography – measurement of carotid intima media thickness, iii)vintravascular ultrasonography, iv) Computed Tomography, v) Magnetic Resonance Imaging 8. ApoA-1 = 110 mg/dL 9. HDL-cholesterol = 35 mg/dL or 0.9 mmol/L 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 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: EXCLUSION CRITERIA Patients meeting any one of the following criteria are not eligible for the study: 1. Patient with LCAT mutation will be excluded 2. Patient who experienced a cardiovascular event within 6 months prior to the onset of screening 3. Patient who experienced stroke or other cerebrovascular event within 1 year prior to the onset of screening 4. Patients with triglycerides level above 500 mg/dL 5. The patient has evidence of clinically significant, uncontrolled or unstable cardiovascular, renal, hepatic (incl. AST or ALT at or above 3x ULN, or bilirubin at or above 2x ULN), gastrointestinal, hematologic, immunological, neurological, endocrine, metabolic or pulmonary disease (as determined by medical history, clinical laboratory or ECG results, or physical examination) or any other medical disorder that would increase the risk associated with taking study medication or would confound the interpretation of study results. 6. Patients with a body mass index (BMI) 40 kg/m2 7. Patients with severe anemia defined as hemoglobin level below or equal to 10 g/dL 8. Any clinically significant abnormal laboratory data, vital signs, physical examination at screening or baseline, which in the opinion of the investigator, would interfere with safety assessments 9. Clinically significant ECG abnormality at screening, including sinus bradycardia (resting heart rate 10% 16. Unexplained creatine phosphokinase level > 3 times the ULN 17. History of malignancy during the 3 years prior to screening, with the exception of basal cell carcinoma of the skin 18. Current alcohol or drug abuse or history thereof within 5 years prior to screening 19. Contraindication to MRI scanning such as imbedded metal (e.g., schrapnel), implanted metal objects (e.g., pacemaker), claustrophobia. 20. Participated in any investigational study or taken an investigational drug within 30 days (or 5 times the half-life of the investigational drug, whatever is longer) 21. Ever received CER-001 within 6 months from the onset of screening 22. Medically non-compliant in the management of their disease in the investigator’s opinion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of 24 weeks treatment with CER-001 on carotid Mean Vessel Wall Area (MVWA) as compared to placebo using 3T magnetic resonance imaging (3T-MRI); To evaluate the safety and tolerability of CER-001 administered for 24 weeks ;Secondary Objective: To evaluate the effect of 8 weeks and 48 weeks treatment with CER-001 on MVWA as compared to placebo using 3T-MRI; To evaluate the effect of 8 weeks, 24 weeks and 48 weeks treatment with CER-001 on femoral artery as compared to placebo using 3T-MRI; To evaluate the effect of 24 weeks treatment with CER-001 in the target (plaque) to background (blood) ratio (TBR) from an index vessel (either right carotid, left carotid) based on the standardized 18FDG uptake measured with PET/CT; To evaluate safety and tolerability of CER-001 administered for 48 weeks Other objectives: To evaluate safety and tolerability of 72 week treatment with CER-001. To evaluate the effect of 72 week treatment with CER-001 on MVWA using 3T-MRI; To evaluate the effect of 72 week treatment with CER-001 on femoral artery using 3T-MRI;;Primary end point(s): PRIMARY EFFICACY PARAMETER: The primary efficacy parameter of this study will be the change from baseline after 24 weeks treatment with CER-001 on carotid Mean Vessel Wall Area (MVWA) as compared to placebo using 3T-MRI when administered to patients with genetically defined FPHA. ;Timepoint(s) of evaluation of this end point: After 24 weeks treatment with CER-001 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): SECONDARY EFFICACY PARAMETERS: • Change from baseline after 8 week and 48 week treatment with CER-001 on MVWA as compared to placebo using 3T-MRI when administered to patients with genetically defined FPHA. • Change from baseline after 8, 24 and 48 week treatment with CER-001 on femoral artery as compared to placebo using 3T-MRI when administered to patients with genetically defined FPHA. • Change from baseline at 24 weeks in the TBR from an index vessel (either right carotid or left carotid) based on the standardized 18FDG uptake measured with PET/CT in patients with genetically defined FPHA. SECONDARY SAFETY PARAMETERS: • Incidence and severity of AEs from routine monitoring. • Incidence of abnormalities and changes from baseline in clinical laboratory parameters from testing of blood and urine, including anti-ApoA-1 antibody. • Incidence of cardiovascular events. OTHER EFFICACY PARAMETERS: • Change from baseline after 72 week treatment with CER-001 on carotid Mean Vessel Wall Area (MVWA) using 3T-MRI when administered to patients with genetically defined FPHA • Change from baseline after 72 week treatment with CER-001 on femoral artery using 3T-MRI when administered to patients with genetically defined FPHA;Timepoint(s) of evaluation of this end point: After 8, 24, 48 and 72 week treatment with CER-001 | — |
Countries
Belgium, Canada, France, Israel, Italy, Netherlands, United States
Contacts
Public ContactMs. D. Ekkel
Clinical Trial Service B.V.
Outcome results
None listed