A placebo-controlled, double-blind, randomized trial to evaluate the effect of 300 mg of inclisiran sodium given as subcutaneous injections in subjects with heterozygous familial hypercholesterolemia (HeFH) and elevated low density lipoprotein cholesterol (LDL-C)
- Conditions
- hypercholesterolemia and elevated levels of cholesterol100822061000751010013317
- Registration Number
- NL-OMON48935
- Lead Sponsor
- The Medicines Company
- Brief Summary
Trial is onging in other countries
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 38
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
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 <4.52 mmol/L (<400 mg/dL) at screening.
6. Calculated glomerular filtration rate >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)
8. Subjects not receiving statin must have documented evidence of intolerance
to all doses of at least two different statins
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.
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 <25%.
4. Cardiac arrhythmia within 3 months prior to randomization that is not
controlled by medication or via ablation.
5. Major adverse cardiovascular event within 3 months prior to randomization.
6. Uncontrolled severe hypertension: systolic blood pressure >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, longterm
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 d
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoints:<br /><br>* Percentage change in LDL-C from baseline to Day 510<br /><br>* Tine adjusted percentage change in LDL-C from baseline after Day 90 up to Day<br /><br>540. This is the average percentage change in LDL-C from baseline over the<br /><br>period after Day 90 up to Day 540.</p><br>
- Secondary Outcome Measures
Name Time Method