Hypercholesterolemia MedDRA version: 20.1 Level: LLT Classification code 10020604 Term: Hypercholesterolemia System Organ Class: 100000004861
Conditions
Interventions
Product Name: Inclisiran for Injection
Product Code: Inclisiran for Injection
Pharmaceutical Form: Solution for injection
INN or Proposed INN: INCLISIRAN
CAS Number: 1639324-58-5
Current Sponsor code:
Sponsors
The Medicines Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects may be included in the study if they meet all of the following criteria: 1. Male or female subjects =18 years of age. 2. History of HeFH with a diagnosis of HeFH by genetic testing; and/or a documented history of untreated LDL-C of >190 mg/dL, and a family history of FH, elevated cholesterol or early heart disease may indicate FH (APPENDIX A) 3. Stable on a low-fat diet (eg, NCEP) 4. Serum LDL-C =2.6 mmol/L (=100 mg/dL) at screening 5. Fasting triglyceride 30 mL/min by estimated glomerular filtration rate (eGFR) using standardized clinical methodology. 7. Subjects on statins should be receiving a maximally tolerated dose. Maximum tolerated dose is defined as the maximum dose of statin that can be taken on a regular basis without intolerable adverse events. Intolerance to any dose of any statin must be documented as historical AEs attributed to the statin in question in the source documentation and on the Medical History page of the electronic case report form (eCRF) (see APPENDIX B). 8. Subjects not receiving statin must have documented evidence of intolerance to all doses of at least two different statins (see APPENDIX B). 9. Subjects on lipid-lower therapies (such as a statin and/or ezetimibe) should be on a stable dose for =30 days before screening with no planned medication or dose change during study participation. 10. Subjects must be willing and able to give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures. 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 280 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: Subjects will be excluded from the study if any of the following exclusion criteria apply prior to randomization: 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 Association (NYHA) class 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. 7. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), >3x the upper limit of normal (ULN), or total bilirubin >2x ULN at screening confirmed by a repeat abnormal measurement at least 1 week apart. 8. Severe concomitant noncardiovascular disease that carries the risk of reducing life expectancy to less than 2 years. 9. History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy during the three years prior to randomization. 10. Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least two methods of highly effective contraception (failure rate less than 1% per year) (eg, combined oral contraceptives, barrier methods, approved contraceptive implant, long- term injectable contraception, or intrauterine device) for the entire duration of the study. Exemptions from this criterion: a. Women >2 years postmenopausal (defined as 1 year or longer since last menstrual period) AND more than 55 years of age. b. Postmenopausal women (as defined above) and less than 55 years of age with a negative pregnancy test within 24 hours of randomization. c. Women who are surgically sterilized at least 3 months prior to enrollment. 11. Males who are unwilling to use an acceptable method of birth control during the entire study period (ie, condom with spermicide). 12. Known history of alcohol and/or drug abuse within the last 5 years. 13. Treatment with other investigational products or devices within 30 days or five half-lives of the screening visit, whichever is longer. 14. Planned use of other investigational products or devices during the course of the study. 15. Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to: a. 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). c. Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (eg, uncooperat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the effect of inclisiran treatment on: •LDL-C levels at Day 510 •Time adjusted percent change in LDL-C levels from baseline between Day 90 and Day 540 levels ;Secondary Objective: The secondary objectives of this study are to evaluate the effect of inclisiran on: •PCSK9, total cholesterol, ApoB and non-HDL-C at Day 510 •LDL-C and PCSK9 levels over time to Day 540 •Mean maximum reduction in LDL-C levels •LDL-C and PCSK9 levels over time in individual subjects •Other lipids, lipoproteins, apolipoproteins •Proportion of subjects achieving prespecified LDL-C targets •Safety and tolerability profile of inclisiran ;Primary end point(s): The primary endpoints of this study are: •Percentage change in LDL-C from baseline to Day 510 •Time adjusted percentage change in LDL-C from baseline between Day 90 and Day 540. This is the average percentage change in LDL-C from baseline over the period between Day 90 and Day 540. ;Timepoint(s) of evaluation of this end point: •From baseline to Day 510 •From baseline between Day 90 and Day 540 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: • From baseline to Day 510 • From baseline to Day 540 • From baseline between Day 90 and Day 540 • Safety and tolerability to Day 540 ;Secondary end point(s): The key secondary endpoints of this study are: •Absolute change in LDL-C from baseline to Day 510 •Time adjusted absolute change in LDL-C from baseline between Day 90 and Day 540 •Percentage change from baseline to Day 510 in PCSK9, total cholesterol, ApoB, and non-HDL-C The other secondary endpoints of this study are: •Mean maximum percentage change in LDL-C •Absolute change from baseline to Day 510 in PCSK9, total cholesterol, ApoB and non-HDL-C •Absolute change and percentage change in LDL-C from baseline to each assessment time up to Day 540 •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 Day 510 •Proportion of subjects in each group with greater or equal to 50% LDL-C reduction from baseline •Absolute change and percentage change in other lipids, lipoproteins, apolipoproteins, and PCSK9 from baseline at each subsequent visit to Day 540 •Proportion of subjects in each group who attain global lipid targets for their level of ASCVD risk •Safety and tolerability profile of inclisiran as measured by AEs, SAEs, vital signs, clinical laboratory values, ECG measurements and formation of ADA and subsequent characterization of ADA | — |
Countries
Austria, Canada, Czech Republic, Denmark, France, Israel, Netherlands, Norway, South Africa, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactGlobal Health Science Center
The Medicines Company
Outcome results
None listed