Hypercholesterolemia MedDRA version: 19.0 Level: LLT Classification code 10020604 Term: Hypercholesterolemia System Organ Class: 100000004861
Conditions
Interventions
Product Name: ALN-PCSSC
Product Code: ALN-PCSSC
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ALN-60212
Current Spons
Sponsors
The Medicines Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects = 18 years of age . 2.History of ASCVD or ASCVD-risk equivalents (symptomatic atherosclerosis, Type 2 diabetes, familial hypercholesterolemia, including subjects whose 10-year risk of a cardiovascular [CV] event assessed by Framingham Risk Score * or equivalent has a target LDL-C of 30 mL/min by estimated glomerular filtration rate (eGFR) using standardized local clinical methodology. 6. Subjects on statins should be receiving the maximally tolerated dose (investigator’s discretion). 7. Subjects on lipid-lowering therapies (such as statins and/or ezetimibe) should be on a stable dose for =30 days before screening with no planned medication or dose change during study participation. 8. Willing and able to give written and informed consent before initiation of any study-related procedures and willing to comply with all required study procedures. *By Framingham Risk Score > 20% 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 240 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 240
Exclusion criteria
Exclusion criteria: 1. Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study, and/or put the subject at significant risk (according to investigator’s [or delegate] judgment) if he/she participates in the clinical study. 2. An underlying known disease, or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate) might interfere with interpretation of the clinical study results 3. New York Heart Failure Association (NYHA) class II, III or IV heart failure or last known left ventricular ejection fraction 180 mmHg or diastolic blood pressure >110 mmHg prior to randomization despite anti-hypertensive therapy. 8. Poorly controlled Type II diabetes, ie, glycated hemoglobin A1c (HbA1c) >10.0% prior to randomization. 9. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained alanine aminotransferase (ALT), aspartate aminotransferase (AST), elevation > 2x the upper limit of normal (ULN), or total bilirubin elevation > 1.5x ULN at screening confirmed by a repeat measurement at least one week apart. 10. Serious comorbid disease in which the life expectancy of the subject is shorter than the duration of the trial (eg, acute systemic infection, cancer, or other serious illnesses). This includes all cancers with the exception of treated basal-cell carcinoma occurring >5 years before screening. 11. Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least two methods of contraception (oral contraceptives, barrier methods, approved contraceptive implant, long- term injectable contraception, intrauterine device or tubal ligation)**. Women who are >2 years postmenopausal defined as =1 year since last menstrual period AND if < 55 years old with a negative pregnancy test within 24 hours of randomization or surgically sterile are exempt from this exclusion. 12. Males who are unwilling to use an acceptable method of birth control during the entire study period (ie, condom with spermicide). 13. Known history of alcohol and/or drug abuse within the last 5 years. 14. Treatment with other investigational medicinal products or devices within 30 days or five half lives, whichever is longer. 15. Use of other investigational medicinal products or devices during the course of the study. 16. Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to: a. Inappropriate for this study, including subjects who are unable to communicate or to cooperate with the investigator. b. Unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study (including subjects whose cooperation is doubtful due to drug abuse or alcohol dependency).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Primary Endpoint: Percentage change in LDL-C from baseline to Day 180. ;Timepoint(s) of evaluation of this end point: Included in previous section.;Main Objective: To evaluate the effect of ALN-PCSSC treatment on LDL-C levels at Day 180.; Secondary Objective: To evaluate the effect of ALN-PCSSC on the following: • LDL-C levels at Day 90 •LDL-C levels at other time points •PCSK9 levels over time •Other lipids, lipoproteins, apolipoproteins •The proportion of subjects achieving different global lipid guidelines •Individual responsiveness to different doses •Duration of lipid-lowering effect of different doses •The safety and tolerability profile of ALN-PCSSC | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: • Percentage change in LDL-C from baseline to Day 90 • Percentage change in LDL-C from baseline to Days 14, 30, 60, 104, 120, 150, and 210 • Proportion of subjects in each group with LDL-C greater than 80% of the baseline value at Day 180 and Day 210 • Duration of time on treatment for subjects to return to 80% of baseline or greater LDL-C or PCSK9 protein • Individual responsiveness defined as the number of subjects reaching on treatment LDL-C levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL at Days 90, 120, and 180 • Proportion of subjects in each group with greater or equal to 50% LDL-C reduction from baseline at Days 90, 120, and 180 • Percentage change in PCSK9 levels from baseline to Days 14, 30, 60, 104, 120, 150, 180 and 210 • Percentage change in other lipids, lipoproteins, apolipoproteins from baseline at each subsequent visit to Day 210 • Proportion Proportion of subjects in each group with greater or equal to 50% LDL-C reduction from baseline at Days 90, 120, and 180 ;Timepoint(s) of evaluation of this end point: Included in previous section. | — |
Countries
Canada, Germany, Netherlands, United Kingdom, United States
Contacts
Public ContactGlobal Health Science Center
The Medicines Company
Outcome results
None listed