FRANCIS-ACS Trial: A Study of the Safety and Efficacy of A 002 in Subjects With Acute Coronary Syndromes

FRANCIS-ACS Trial: A Study of the Safety and Efficacy of A 002 in Subjects With Acute Coronary Syndromes

The objective of this study is to evaluate the safety and efficacy of A 002 when added to high dose atorvastatin in subjects with an acute coronary syndrome (ACS)

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 once daily (QD) or placebo tablets in addition to 80 mg atorvastatin QD.

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 will occur at Weeks 2, 4, 8, 12, 16, 20, and 24 post-randomization; and monthly thereafter until study completion.

All enrolled subjects will remain on treatment until all subjects have been treated for a minimum of 24 weeks or until the occurrence of a Major Adverse Cardiac Event (MACE). At that point, all active subjects (those who have not early withdrawn or those that have not already had a MACE) will be brought in for a Final Study Visit. Subjects who complete the Final Study Visit may be eligible to enroll in an open-label extension study for up to 2 years total study drug exposure.

Inclusion Criteria:

• Men and women ≥18 years of age
• A diagnosis of unstable angina, NSTEMI, or STEMI
• Any one of the following criteria: Diabetes, CRP ≥2 mg/L, or metabolic syndrome
• Subjects must be randomized within 96 hours of the index event
• Percutaneous revascularization, if required or planned, must occur prior to randomization

Exclusion Criteria:

- Subjects must NOT meet any of the following exclusion criteria:

• Subjects enrolled in another experimental (interventional) protocol within the past 30 days prior to Screening.
• 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 (e.g., chemotherapy), or radiation therapy.
• The presence of severe liver disease with cirrhosis, recent active hepatitis, active chronic hepatitis, ALT or AST >3 x ULN, biliary obstruction with hyperbilirubinemia (total bilirubin >2 x ULN)
• Active cholecystitis, gall bladder symptoms, or potential hepato-biliary abnormalities
• The presence of severe renal impairment (CrCl <30 mL/min or creatinine >3 x ULN), nephrotic syndrome, or patients undergoing dialysis
• Uncontrolled diabetes mellitus (HbA1c >11% within the last 1 month prior to Screening)
• 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 child-bearing 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, IUD, contraceptive implants, tubal ligation, hysterectomy, a barrier method (diaphragm with spermicidal foam or jelly, or a condom).
• Subjects who have a history of alcohol or drug abuse within 1 year of study entry
• Subjects living too far from participating center or unable to return for follow-up visits
• Subjects who in the opinion of the Investigator are a poor medical or psychiatric risk for therapy with an investigational drug, are unreliable, or have an incomplete understanding of the study which may affect their ability to take drugs as prescribed or comply with instructions
• Known HIV, Hepatitis B or C virus, or tuberculosis infection
• Acute bacterial, fungal or viral infection
• Any current statin therapy at maximum recommended dosage. For atorvastatin, fluvastatin, lovastatin, pravastatin and simvastatin 80 mg QD at the time of the index event and for rosuvastatin 20 mg QD to 40 mg QD
• Drugs that are potent inhibitors of cytochrome P450 unless they can be withdrawn
• Subjects with NYHA Class III or IV heart failure, or LVEF <30
• Subjects with moderate or severe aortic stenosis, aortic regurgitation, mitral stenosis or mitral regurgitation
• Ventricular arrhythmias requiring chronic drug treatment or ICD
• Subjects with no stenosis or stenosis <50% on angiography
• Subjects with a pacemaker or persistent LBBB
• LDL-C >200 mg/dL (5.2 mmol/L)
• Fasting triglyceride levels of ≥400 mg/dL (4.5 mmol/L)