The objective of this study is to evaluate the safety and efficacy of A-002 when added to atorvastatin plus standard-of-care in subjects with an ACS. Specifically this study will examine the effect of treatment on morbidity and mortality as defined…
ID
Source
Brief title
Condition
- Cardiac disorders, signs and symptoms NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of the study is to determine whether 16 weeks of
treatment with A-002 plus atorvastatin
and standard of care is superior to placebo plus atorvastatin and
standard of care for reducing the hazard of the first occurrence of the
combined endpoint of cardiovascular death,
non-fatal myocardial infarction, non-fatal stroke, or documented unstable
angina with objective evidence of
ischemia requiring hospitalization.
Secondary outcome
A secondary objective of the study is to determine whether A-002 plus
atorvastatin and standard of care is
superior to placebo plus atorvastatin and standard of care for reducing the
occurrence of the hazard of the
combined endpoint of all-cause mortality, non-fatal myocardial infarction,
non-fatal stroke or documented
unstable angina with objective evidence of ischemia requiring hospitalization
or multiple occurrences of the nonfatal
components of the composite primary endpoint
Background summary
Recently the safety and efficacy of A-002 has been established in 2 studies of
subjects with stable coronary artery disease (CAD) in which significant
decreases in secretory phospholipase A2 (sPLA2), low-density
lipoprotein-cholesterol(LDL-C), as well as C-reactive protein (CRP) were
documented
(Rosenson 2009). The potential clinical importance of reducing inflammation has
also been reported in the setting of primary prevention (Ridker 2008) as well
as the acute setting (PROVE-IT [Cannon 2004] and Kinlay 2003). These data along
with the literature documenting the association between elevated levels of
sPLA2 and cardiovascular risk in subjects with acute coronary syndrome
(ACS)(Kugiyama 2000; Mallat 2005), support the investigation of the safety and
efficacy of A-002 in a study of subjects presenting with an ACS.
Intervention with a specific sPLA2 inhibitor could salvage non-lethally
jeopardized cells following an ischemic episode and thus could result in a
reduction in the area of infarcted damage.
Study objective
The objective of this study is to evaluate the safety and efficacy of A-002
when added to atorvastatin plus standard-of-care in subjects with an ACS.
Specifically this study will examine the effect of treatment on morbidity and
mortality as defined by the respective primary and secondary efficacy composite
variables: cardiovascular death, non-fatal myocardial infarction, non-fatal
stroke, or documented unstable angina with objective evidence of ischemia
requiring urgent hospitalization; and all-cause mortality, non-fatal myocardial
infarction, non-fatal stroke, or documented unstable angina with objective
evidence of ischemia requiring hospitalization.
Study design
This is a double-blind randomized parallel group placebo controlled study in
subjects presenting with an ACS. Subjects will be randomized to receive either
A-002 500 mg QD or placebo tablets in addition to atorvastatin plus
standard-ofcare. Randomization must occur within *96 hours of hospital
admission for the index ACS event, or if already hospitalized, within *96 hours
of index event diagnosis.
Follow-up visits or blood draws will occur at 6, 12, 24, 48, 72, 96 hours (for
the first 1500 patients) postrandomization and Weeks 1, 2, 4, 8, and 16. All
lipid lowering therapies other than atorvastatin must be withdrawn prior to
randomization.
All enrolled subjects will be followed until they have completed 16 weeks of
treatment. The survival status of all subjects who have not died or withdrawn
consent will be ascertained 6 months after they finish treatment.
Intervention
Following confirmation of eligibility, subjects will be randomized to A-002 500
mg QD or placebo plus atorvastatin. The dose of atorvastatin to be used will be
at the discretion of the treating clinician but must be *20 mg daily. There
will be an opportunity to adjust the atorvastatin dose at Week 8 if LDL-C
levels remain above 100 mg/dL, but otherwise it must remain stable throughout
the 16-week duration of the study. All other lipid lowering therapies (e.g.,
ezitimibe, fibrates, niacin, sequestrants) must be withdrawn prior to
randomization and are not permitted during the treatment period of the study
(16 weeks).
Study burden and risks
Patient should start the use of Atorvastatin (which might mean a switch of
statin) and start the use of the study medication at the same time.
The patient should be able to visit the clinic and have blood withdrawn during
each visit.
25801 Industrial Boulevard, Suite B
94545, Hayward, CA
US
25801 Industrial Boulevard, Suite B
94545, Hayward, CA
US
Listed location countries
Age
Inclusion criteria
1. Men and women *40 years of age
2. Written informed consent from the subject
3. All subjects must have the presence of at least one of the following risk
factors:
i. Diabetes Mellitus or
ii. Presence of any 3 of the following characteristics of metabolic syndrome
- Waist circumference >102 cm in males, >88 cm in females
- Serum triglycerides *150 mg/dL (*1.7 mmol/L)
- HDL-C <40 mg/dL (<1 mmol/L) in males, <50 mg/dL (<1.3 mmol/L) in females
- Blood pressure *130/85 mmHg
- Plasma glucose *110 mg/dL (*6.1 mmol/L) or
- history of cerebrovascular disease (stroke or TIA) o
- HDL <42 mg/dL or
- eGFR <60 mL/min or
- angiographic evidence of CAD (>50%)
- history of peripheral vascular disease or
- previous CABG or
- previous documented myocardial infarction or
- previous coronary revascularization
4. Subjects must be randomized within *96 hours of hospital admission for the index event, or if already hospitalized, within *96 hours of index event diagnosis
5. Percutenous revascularization, if required or planned, must occur prior to randomization
Exclusion criteria
1. Subjects enrolled in another experimental (interventional) protocol within the past 30 days prior to Screening.
2. Subjects treated for cancer within the previous 5 years except for skin basal cell carcinoma or carcinoma in situ of the cervix, with measures other than a minor, complete surgical excision or radiation therapy, (e.g., chemotherapy).
3. The presence of any severe liver disease with cirrhosis, active hepatitis, active chronic hepatitis, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 x ULN, biliary obstruction with
hyperbilirubinemia (total bilirubin >2 x ULN)
4. Active cholecystitis, gall bladder symptoms, or any hepato-biliary
abnormalities
5. The presence of severe renal impairment (creatinine clearance
[CrCl] <30 mL/min or creatinine >3 x ULN), nephrotic syndrome, or subjects
undergoing dialysis
6. Uncontrolled diabetes mellitus (known hemoglobin A1c [HbA1c] >11%
within the last 1 month prior to Screening)
7. Females who are nursing, pregnant, or intend to become pregnant during
the time of the study, or females of child-bearing potential who have a
positive pregnancy test during screening evaluation. Women of childbearing
potential must also use a reliable method of birth control during the
study and for 1 month following completion of therapy. A reliable method
for this study is defined as one of the following: oral or injectable
contraceptives, intrauterine device (IUD), contraceptive implants, tubal
ligation, hysterectomy, a double barrier method (diaphragm with spermicidal
foam or jelly, or a condom).
8. Subjects who have a history of alcohol or drug abuse within 1 year of study entry
9. Subjects living too far from participating center or unable to return for followup visits
10. Subjects who have a history of statin intolerance or a significant myopathy or rhabdomyolysis with any lipid-altering drugs
11. Subjects currently treated with the maximum labeled dose of a statin and not at LDL-C target for their level of risk as defined by NCEP ATP
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-016812-18-NL |
| CCMO | NL32613.018.10 |