CER-001 Therapy as a Novel Approach to Treat Genetic Orphan Diseases

Phase 3, Multicenter, Randomized, 48 Week, Double Blind, Parallel Group, Placebo Controlled Study to Evaluate Efficacy and Safety of CER-001 on Vessel Wall Area in Patients With Genetically Defined Familial Primary Hypoalphalipoproteinemia

The purpose of this study is to assess the impact of 29 intravenous infusions of CER-001 vs. placebo, given at weekly (9 infusions) and biweekly (20 infusions) intervals on carotid vessel wall area as measured by 3TMRI, when administered to patients with familial primary hypoalphalipoproteinemia with proven CVD and appropriate background lipid-lowering therapy.

Subjects will be required to have acceptable baseline 3TMRI imaging of carotid arteries. Subjects meeting all eligibility criteria will be randomized to receive CER-001 or placebo (2:1 randomization scheme). Randomized subjects will return weekly for a total of 9 infusions and then biweekly for an additional 20 infusions. 3TMRI imaging of the carotid and femoral arteries will be performed at Week 8, Week 24 (primary endpoint) and Week 48. The total study duration from randomization can range from 50 to 54 weeks for patients completing the study as designed.

Main Inclusion Criteria:

• Male and female patients, aged 18 and above.
• ApoA-I < 70 mg/dL
• Symptomatic or asymptomatic cardiovascular disease
• Diagnosis of genetically confirmed HDL-c deficiency due to defects in genes coding for ABCA1 and/or ApoA-1
• Stable doses of lipid lowering therapies for at least 6 weeks prior to baseline procedures

Main Exclusion Criteria:

• Females of childbearing potential
• Patients with LCAT mutations
• Patients who experienced recent cardiovascular or cerebrovascular events
• Hypertriglyceridemia (>500 mg/dL)
• Severe anemia (Hgb < 10 g/dL)
• Uncontrolled diabetes (HbA1c >10%)
• Congestive heart failure (NYHA class II or higher)
• Contraindication for MRI scanning (e.g., implanted metal objects, claustrophobia)