A Phase 3 multi-centre study to test the efficacy, safety and tolerability of Bococizumab (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
- atherosclerosisMedDRA version: 19.0Level: LLTClassification code 10003601Term: AtherosclerosisSystem Organ Class: 100000004866Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2013-002795-41-BE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 11000
1. Informed Consent
There must be evidence of personally signed and dated informed consent documents for both the pre-screening and screening visits, indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study. The pre-screening visit informed consent form will be limited to study activities up until the screening visit. The screening visit informed consent form will cover all aspects of the study.
Subjects should be reconsented if there are modifications to the original
informed consent document, at the next available opportunity.
2. Compliance
Subjects must be willing and able to comply with scheduled visits,
treatment plan, laboratory tests, and other study procedures.
3. Age
Subjects who have had a prior CVD event must be men or women age=
the legal age of majority (legal adulthood), in the subject's country.
Subjects who have not had a prior CVD event, must be age =50 years if a man, and must be age =60 years, if a woman, with the following
exceptions:
Subjects who have not had a prior CVD event, but who have a conditions
of elevated LDL-C, (heterozygous familial hypercholesterolemia [heFH]
or a history of LDL-C =190 mg/dL [4.9 mmol/L]) should be = 35 years of
age if a man, and = 45 years of age, if a woman.
4. Acceptance of administration of investigational product
Subjects must be willing and able to self-administer or be administered
sub-cutaneous injections of IP.
5. Requirements for background lipid lowering treatment
There should be no plans at the time of pre-screening and randomization to modify the dose of statin for the duration of the trial. Unless the background lipid lowering treatment exceptions described below are met, subjects must be treated with one of the following highly effective statins at the specified daily doses for =4 weeks prior to the prescreening visit:
-atorvastatin, at least 40 milligrams (mg) once a day;
- rosuvastatin, at least 20 mg, once a day;
- simvastatin, at least 40 mg, once a day or, if a subject has been on that dose for >1 year, 80 mg, once a day.
Combination medications that contain atorvastatin, rosuvastatin, or
simvastatin components described at the aforementioned doses will be
permitted.
Background lipid lowering treatment exceptions
The following background lipid lowering treatment exceptions are
permitted:
-Lower doses of statins due to partial statin intolerance
Subjects may be on a lower dose of one of the highly effective statins
described above if there is documented intolerance to any one of them
(atorvastatin, rosuvastatin, or simvastatin) at the aforementioned, or
lower, doses. Intolerance to any dose of any statin must be documented as historical adverse events attributed to the statin in question, in the source documentation and case report form (CRF).
- Regulatory limitations
Subjects may be on a lower dose of one of the highly effective statins
described above if the highest locally approved dose for one of the
stated statins is lower than those doses shown above (eg, in Japan,
atorvastatin 20 mg, once a day, is the highest locally approved dose) or
due to label restrictions.
- Alternative statins
Subjects may be treated with other statins (pravastatin, fluvastatin,
pitavastatin, or lovastatin), different from the highly effective statins
listed above, if there is documented intolerance to any two different
highly effective statins (atorvastatin, rosuvastatin, simvastatin)
1. Personnel involved in the conduct of the study
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. Exclusionary prior CV events or planned revascularization procedures
-A planned coronary (PCI or CABG) or other arterial revascularization;
-Myocardial infarction, stroke, or any non-coronary arterial
revascularization= 30 days prior to screening;
-Coronary revascularization= 90 days prior to screening;
- Subjects with SAEs that would have potentially met the criteria for a
CVD event (as defined in Appendix 4), between Visit 0 and Visit 5, should be excluded. Such subjects may be rescreened at a later date.
3. Participation in prior clinical research studies
Participation in other studies involving small molecule investigational
drug(s) (Phases 1-4) within 1 month, or five half-lives, of Visit 1,
whichever is longer; any participation in a cholesteryl ester transfer
protein (CETP) inhibitor within 1 year of Visit 1; or any biological agents
within 6 months or 5 half-lives, of Visit 1, whichever is longer (the
investigator should refer to documents provided by the subject on the
other study to determine the IP half-life). If the blind of the prior study
has been broken and the investigator provides documentation that the
subject received placebo, the potential subject can be included,
regardless of when participation occurred.
4. Other exclusionary conditions
Other severe, acute, or chronic medical or psychiatric condition or
laboratory abnormality that may increase the risk associated with study
participation or IP 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. Childbearing potential and/or breast feeding
Pregnant female subjects; breastfeeding female subjects; male subjects
with partners currently pregnant who are sexually active; male subjects
able to father children and female subjects of childbearing potential,
who are at risk of pregnancy with their partners and 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 IP.
6. Latex sensitivity
Latex sensitive individuals (due to potential for exposure to natural dry
rubber in the prefilled syringe cap of IP, during administration).
7. Apheresis
Undergoing lipid apheresis, within 6 weeks of pre-screening, or planned
start of lipid apheresis.
8. Severe congestive heart failure
Congestive heart failure of New York Heart Association (NYHA) Class IV,
or if there is prior documentation of left ventricular ejection fraction
(LVEF) of <25%, measured by imaging. For subjects who have had serial
assessments of LVEF, only the most recent study is used for the
purposes of this exclusion requirement.
9. Dialysis
Potential subjects with end stage renal disease on dialysis.
10. Chronic renal insufficiency
Potential subjects with an eGFR of <30 ml/min/1.73m2 by MDRD formula at Visit 1.
11. Hypertension
Poorly controlled hypertension at any screening visit or at randomization, defined as the average of two systolic blood pressure (BP) measurements >180 mmHg or the average of two diastolic
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