Hypercholesterolemia
Conditions
Interventions
Product Code: REGN727/SAR236553
Pharmaceutical Form: Solution for injection in pre-filled syringe
CAS Number: 1245916-14-6
Current Sponsor code: REGN727
Sponsors
Regeneron Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Man or woman between the ages of 18 and 70 years, inclusive - A history of molecularly confirmed PCSK9 GOFm - Plasma LDLc levels =70 mg/dL (x 0.0259 mmol/L) and considered to be not at goal by the investigator - Body mass index =18.0 and =40.0 kg/m2 at the screening visit (visit 1 [day -28 to 15]) - Systolic Blood Pressure =150 mm Hg and diastolic BP =95 mm Hg - Willing to refrain from the consumption of no more than 2 standard alcoholic drinks in any 24-hour period for the duration of the study. A standard alcoholic drink is the equivalent of 12 ounces beer, 5 ounces of wine, or 1.5 ounces of hard liquor - Willing to refrain from the consumption of alcohol for 24 hours before each study visit - Willing to maintain their usual stable diet and exercise regimen throughout the study - Willing and able to comply with clinic visits and study-related procedures - Provide signed informed consent 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 11 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: - Serum triglycerides >350 mg/dL (x 0.01129 mmol/L) measured after an 8 to 12 hour fast - History of heart failure (New York Heart Association Class II-IV) within the 12 months before the screening visit - History of myocardial infarction, acute coronary syndrome, unstable angina pectoris, stroke, peripheral vascular disease, transient ischemic attack, or cardiac revascularication within the 6 months before the screening visit - History of uncontrolled, clinically significant cardiac dysrhythmias or clinically significant recent changes in electrocardiogram 6 months before the screening visit - History of undergoing LDL apheresis within 3 months before the screening visit - Uncontrolled diabetes mellitus with hemoglobin A1C (HbA1c) >8.5% at the screening visit - Thyroid stimulating hormone (TSH) >1.5 x upper limit of normal at the screening visit - Alanine aminotransferase or aspartate aminotransferase >2 x upper limit of normal at the screening visit - Creatine phosphokinase >3 x upper limit of normal at the screening visit - Known sensitivity to monoclonal antibody therapeutics - Participation in a clinical research study evaluating an investigational drug within 30 days, or at least 5 half-lives of the investigational drug, before the screening visit, whichever is longer - Known to be positive for human immunodeficiency virus, hepatitis B virus, or hepatitus C virus - History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases - Pregnant or breast-feeding women - Sexually active man or woman of childbearing potential who is unwilling to practice adequate contraception during the study - Any medical or psychiatric condition which, in the opinion of the investigator, would place the patient at risk, interfere with patient’s participation in the study or interfere with the interpretation of the study results
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The incidence and severity of TEAEs in patients treated with REGN727 reported between the first dose and the end-of-study visit 2. Percent change in ApoB100 from day 1 (baseline) to day 15 for group A compared to group B 3. Percent change in non-HDL-C from day 1 (baseline) to day 15 for group A compared to group B 4. Percent change in total cholesterol from day 1 (baseline) to day 15 for group A compared to group B 5. Percent change in ApoB100/ApoA1 ratio from day 1 (baseline) to day 15 for group A compared to group B 6. Trough concentrations of total REGN727 following repeat SC dosing with REGN727 throughout the study 7. Immunogenicity of repeat SC dosing with REGN727 throughout the study ; Timepoint(s) of evaluation of this end point: Items 2, 3, 4, 5 in section E.5.2: 14 days Items 1, 6, 7 in section E.5.2: 55 days | — |
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: - The safety and tolerability of subcutaneously administered REGN727 - The effect of REGN727 on other serum lipids and apolipoproteins - The PK profile of REGN727 - The immunogenicity of REGN727 ;Primary end point(s): percent change in direct (ultracentrifuged) serum LDL C from day 1 (baseline) to day 15 for group A compared to group B. ;Timepoint(s) of evaluation of this end point: 14 days;Main Objective: To assess the effect of REGN727 on serum Low-density lipoprotein cholesterol in patients with autosomal domianant hypersholesterolemia and gain-of-function mutations in the PCSK9 gene. | — |
Countries
France, United States
Contacts
Public ContactDirection des opérations Cliniques
sanofi-aventis France
Outcome results
None listed