This study is a multicenter, randomized study in subjects with high cholesterol receiving highly effective statins to assess the efficacy, safety and tolerability of RN316 (PF-04950615) to lower LDL-C.
- Conditions
- Primary Hyperlipidemia or mixed DyslipidemiaMedDRA version: 17.1Level: LLTClassification code 10020667Term: HyperlipidemiaSystem Organ Class: 100000004861MedDRA version: 17.1Level: LLTClassification code 10058110Term: DyslipidemiaSystem Organ Class: 100000004861Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2014-000478-20-FI
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 690
Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Males and females = 18 years of age where permitted by law.
4. With primary hyperlipidemia or mixed dyslipidemia.
5. Subjects must be on a stable dose of either simvastatin 40 mg or higher, rosuvastatin 10 mg or higher, atorvastatin 20 mg or higher, or pravastatin 40 mg or higher for at least 6 weeks prior to screening.
- There should be no plans at the time of screening and randomization to modify
the dose of statin for the duration of the trial.
6. Subjects should be at high or very high risk of incurring a CV event, defined as:
a. Known CVD or CVD risk equivalents:
- Known history of CVD.
- Coronary heart disease: history of acute myocardial infarction, or evidence of silent myocardial infarction or myocardial ischemia, or history of unstable angina and stable angina pectoris, or history of coronary procedures (coronary angioplasty and coronary artery surgery), or;
- Other clinical atherosclerotic diseases: peripheral arterial disease, or abdominal aortic aneurysm, or carotid artery disease (symptomatic [eg, transient ischemic attack or stroke of carotid origin] or >50 percent stenosis on angiography or ultrasound), or likely other forms of clinical atherosclerotic disease (eg, renal artery disease), Type 2 or Type 1 diabetes, or;
- Chronic kidney disease (CKD), defined as glomerular filtration rate (GFR) calculated by Modification of Diet in Renal Disease (MDRD) formula between 30 and 60 mL/min/1.73m2 (inclusive).
b. Presence of multiple risk factors:
Subjects who do not have past CVD disease or CVD risk equivalents but have 3 or more of the risk factors from the list below:
- Current cigarette smoking defined as any smoking for 30 days or more at the time of screening.
- HDL-C <40 mg/dL (<1.0 mmol/L) at screening or TC/HDL-C ratio>/=6.
- Family history of premature Coronary Heart Disease (CHD in male first-degree relative <55 years; CHD in female first-degree relative <65 years).
- Age (men =55 years; women =65 years).
- hs-CRP >2.0 mg/L at screening.
7. Lipids should meet the following criteria on a background treatment with a statin:
- Fasting LDL-C >/=100 mg/dL (2.59 mmol/L) at 2 screening visits (screening visits S1 and S3) and the value at the third screening visit (S3) within 7 days (±3 days) of randomization must not be lower or higher than 20% of this initial value (in order to control the variability related to the fasting LDL-C assay), as described in Section 7.1.
Note: If fasting LDL-C at screening visit S3 is lower or higher than 20% of the initial value, LDL-C can be repeated once (within 7 days of randomization), and the subject is eligible if the value of this repeat test is within 20% (inclusive) of the value at screening visit S3.
- All subjects must have fasting TG =400 mg/dL (4.51 mmol/L) at the third screening visit (S3).
8. Male and female subjects of childbearing potential must agree to use
Subjects presenting with any of the following will not be included in the study:
1. Subjects who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the trial.
2. Participation in other studies involving small molecule investigational drug(s) (Phases 1-4) within 1 month or 5 half lives, whichever is longer, except for cholesteryl ester transfer protein (CETP) inhibitors (indefinitely), or biological agents within 6 months or 5 half lives, whichever is longer before the current study begins and/or during study participation (the investigator should refer to documents provided by the subject on the other study to determine the investigational product half life). If the blind has been broken and the Investigator knows (with documentation) that the subject received placebo, he/she can be included.
3. Subjects with prior exposure to PF-04950615 or other investigational PCSK9 inhibitor.
4. Subjects who are unable to receive injections, as either a self-injection, or administered by a family member, or home caregiver.
5. History of a cardiovascular or cerebrovascular event or procedure (eg, myocardial infarction, stroke, transient ischemic attack, angioplasty) during the past 90 days.
6. Congestive heart failure, New York Heart Association functional class IV, or Left Ventricular Ejection Fraction measured by imaging <25%.
7. Poorly controlled hypertension at any screening visit or at randomization (defined as the average of two systolic blood pressure measurements greater than 160 mm Hg or the average of two diastolic blood pressure measurements greater than 100 mm Hg, even with treatment). Subjects who have hypertension and are controlled on stable dosages of anti hypertensive medications can be included. An additional blood pressure (BP) may be performed within the hour or at the completion of the office visit, to confirm a reading.
8. History of hemorrhagic stroke or lacunar infarct.
9. Current untreated hypothyroidism or thyroid stimulating hormone (TSH) > upper limit of normal (ULN) at screening. Subjects who are treated and well controlled should be on the stable dose of thyroid hormone for at least 6 months.
10. Current history of alcoholism or drug addiction according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria within 12 months prior to screening. Use of any recreational drugs within 12 months prior to screening.
11. History of cancer within the last 5 years (except for cutaneous basal cell or squamous cell cancer resolved by excision).
12. Medical history of positive testing for Human immunodeficiency virus (HIV).
13. Any disease or condition that might compromise the hematological, renal, hepatic, pulmonary, endocrine, central nervous, immune, or gastrointestinal systems (unless deemed not clinically significant by the Investigator and/or the Sponsor) or confound the interpretation of the study results. Examples of such conditions include but are not limited to nephrotic syndrome, uncontrolled diabetes, excessive alcohol consumption,
cholestatic liver disease, unstable mental illness.
14. Use of statins other than atorvastatin, rosuvastatin, simvastatin, pravastatin or use of red yeast rice.
15. Undergoing apheresis or have planned start of apheresis.
16. Initiation of, or change in, non lip
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method