A Phase 3 multi-centre study to test the efficacy, safety and tolerability of PF-04950615 administered subcutaneously in reducing the occurrence of major cardiovascular events due to clogging up of arteries by fatty substances in high risk subjects.
- Conditions
- MedDRA version: 16.1Level: LLTClassification code 10003601Term: AtherosclerosisSystem Organ Class: 100000004866atherosclerosisTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2013-002646-36-ES
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 12000
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. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Age: men or women aged ? 18 years for those with a confirmed prior CVD event; or men aged ? 55 years, or women, aged ? 65 years with a CVD risk equivalent.
4. Willing and able to self-administer or be administered sub-cutaneous injections of investigational product.
5. Must be treated with atorvastatin, rosuvastatin, or simvastatin, 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, or that the subject is at his or her LDL-C or non-HDL-C target; and no dose should be lower than atorvastatin 20 mg, rosuvastatin 20 mg, or simvastatin 40 mg, once a day.
a. Subjects on simvastatin 80 mg must have been on this dose for > 1 year before
screening.
b. 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.
c. Source records and case report form (CRF) documentation of the above, must be shown.
6. Qualifying CV risk factor: prior CVD event.
A prior CVD event must be documented by source documentation that includes an anonymized hospital discharge summary describing the qualifying index CVD event diagnosis or surgical event and that includes documentation of the event?s date of occurrence.
Qualifying prior CVD event:
a. greater than thirty days but no more than five years post prior myocardial infarction as defined by the universal definition of MI excluding those with MI due to cocaine abuse or vasospasm) or ischemic stroke, as documented by hospital discharge summary and brain imaging scan
b. greater than one year but no more than five years post previous cardiac revascularization including PCI or CABG, as documented by hospital discharge summary c. pre-existing arterial revascularization, documented as a carotid, or peripheral artery revascularization, as defined as surgery or stent placement and documented by hospital discharge summary (at least one month [30 days] but no more than five years prior to screening)
7. Qualifying CV risk factor: CVD risk equivalent with two additional risk factors: Type I or Type II diabetes mellitus, as defined per local diabetes guidelines (eg, American Diabetes Association [ADA] in the U.S.A, European Association for the Study of Diabetes [EASD] in the European Union [E.U.]) heterozygous familial hypercholesterolemia (heFH), subjects with symptomatic peripheral vascular disease
or chronic kidney disease (with a glomerular filtration rate of ?30 and ?60 mL/min/1.73m2, based on the screening visit measurement of creatinine, as calculated by Modification of Diet in Renal Disease [MDRD] formula, and not on dialysis) and ?55 years of age for men and ?65 years of age for women, with at least two of the following additional risk factors for CVD:
a. Evidence of coronary artery stenoses of > 50% narrowing in at least two major coronary arteries as documented by coronary artery imaging;
b. Current cigarette smoking, defined as smoking for 30 days or more (any number
of cigarettes) at the time of screening;
c. HDL-C < 40 mg/dL (< 1.0 m
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. A planned coronary (PCI or CABG) or other arterial revascularization.
3. Participation in other studies involving molecule investigational drug(s) (Phases 1-4) within 1 month, any participation in a cholesteryl ester transfer protein inhibitor trial for any length of time, or biological agents within 6 months or 5 half lives, whichever is longer before the current study begins and/or during study participation. If the blind has been broken and the investigator knows (with documentation) that the subject received placebo, he/she can be included.
4. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
5. Pregnant females; breastfeeding females; males and females of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for 63 days after last dose of investigational product.
6. Latex sensitive individuals (due to potential for exposure to natural dry rubber in the prefilled syringe cap of investigational product, during administration).
7.Potential subjects with an LDL-C < 70 mg/dL (< 1.8 mmol/L) or ? 100 mg/dL (2.6 mmol/L or non-HDL-C < 100 mg/dL (2.6 mmol/L) or ? 130 mg/dL (3.4 mmol/L) at Visit 1 or Visit 3.
8. Undergoing lipid apheresis or planned start of lipid apheresis.
9. Congestive heart failure of New York Heart Association (NYHA) Class IV, or left ventricular ejection fraction (LVEF) of <25%, measured by imaging.
10. Potential subjects with end stage renal disease on dialysis.
11. Potential subjects with chronic renal insufficiency and a creatinine clearance of < 30 ml/min/1.73m2 by MDRD formula.
12. Poorly controlled hypertension (defined as the average of two systolic blood pressure (BP) measurements greater than 160 mm Hg or diastolic BP 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. BP measurement may be repeated up to three times within the hour or at the completion of the office visit, to confirm a reading.
11. A prior history of hemorrhagic stroke.
12. Plans to donate blood during the study.
13. Current history of alcoholism or drug addiction according to 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.
14. Medical history of positive testing for human immunodeficiency virus.
15. Subjects with prior exposure to PF-04950615 (RN316) or other investigational PCSK9 inhibitor.
16. Subjects who are receiving routine intramuscular(IM) injections or for whom IM therapy is anticipated during the course of the study. Elevations of Creatinine Kinase(CK) i
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