A phase 3 study investigating the efficacy, safety and tolerability of PF-04950615 in patients with elevated levels of cholesterol in the blood caused by a defective gene
- Conditions
- Heterozygous Familial HypercholesterolemiaMedDRA version: 14.1Level: LLTClassification code 10020604Term: HypercholesterolemiaSystem Organ Class: 100000004861Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2013-002644-87-IT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 300
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 legal 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.
4.With previously diagnosed HeFH phenotype as defined according to the Simon Broome criteria, described in Appendix 2 or a genetic diagnosis of HeFH.
5.Subjects are required to be treated with atorvastatin, simvastatin, or rosuvastatin at the highest locally approved dose. If at a lower dose, there must be documentation that the subject is receiving a maximally tolerated dose of the aforementioned statins; and no dose should be lower than atorvastatin 20 mg, rosuvastatin 20 mg, or simvastatin 40 mg.
•Subjects on simvastatin 80 mg must have been on this dose for >1 year before screening.
•All subjects must be on a stable dose 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.
•Source records and case report form (CRF) must show documentation of the requirements shown above.
6.Subjects should be at high or very high risk of incurring a CV event, defined as:
•Known history of CVD based on any one of the below:
•Coronary heart disease: history of acute myocardial infarction, evidence of silent myocardial infarction or myocardial ischemia, history of unstable angina and stable angina pectoris, and history of coronary procedures (coronary angioplasty and coronary artery surgery);
•Other clinical atherosclerotic diseases: peripheral arterial disease, abdominal aortic aneurysm, carotid artery disease (symptomatic [eg, transient ischemic attack or stroke of carotid origin] or >50 percent stenosis on angiography or ultrasound), and likely other forms of clinical atherosclerotic disease (eg, renal artery disease).
OR
•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).
7.Lipids should meet the following criteria on a background treatment with a statin at the 2 screening visits:
•Subjects at the highest approved dose of statins described in 5, above:
•Fasting LDL C =70 mg/dL (1.81 mmol/L) at both screening visits and the value at the second screening visit within 7 days of randomization must not be lower or higher than 20% of this initial value, as described in Section 7.1 of the protocol.
•Subjects not at the highest approved dose of statins described in 5, above:
•Fasting LDL C =77 mg/dL (1.99 mmol/L) at both screening visits and the value at the second screening visit within 7 days of randomization must not be lower or higher than 20% of this initial value, as described in Section 7.1.
•Fasting TG = 400 mg/dL (4.5 mmol/L) at the second screening visit within 7 days of randomization.
8.Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at le
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 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 (RN316) or other investigational PCSK9 inhibitors.
4. Subjects who are unable to receive injections, as either a self-injection, or administered by a family member, health care assistant or health care provider.
5. History of a cardiovascular or erebrovascular event or procedure (eg, Myocardial infarction, stroke, transient ischemic attack, angioplasty) during the past 30 days.
6. Congestive heart failure, New York Heart Association (NYHA) 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. Subjects may be permitted into the study if in the Principal Investigator’s opinion the assessment(s) are not clinically significant.
Blood pressure (BP) may be repeated up to three times within the hour or at the
completion of the office visit, to confirm a reading.
8. Any history of hemorrhagic stroke.
9. Any history of hypothyroidism or thyroid stimulating hormone (TSH) >1X Upper Limit
of Normal (ULN) at screening.
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 and
cholestatic liver disease.
14. Use of statins other than atorvastatin, rosuvastatin or simvastatin.
15. Undergoing apheresis or have planned to start apheresis. 16. Initiation of, or change in, non lipid lowering prescription drugs, herba
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