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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Familial Hypoalphalipoproteinemia

Intervention / Treatment
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* Drug: CER-001
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CER-001<br>CER-001 infusion; 9 weekly infusions followed by 20 biweekly infusions | Drug: CER-001<br>* Recombinant human apoA-I/phospholipid complexes<br>* Other names: CAS 138-3435-67-3;|
| Placebo Comparator: Placebo<br>Saline infusion; 9 weekly infusions followed by 20 biweekly infusions | Drug: Placebo<br>* 0.9% Sodium Chloride Injection, USP<br>* Other names: Normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mmean vessel wall area (MVWA) of the carotid artery | Change from baseline to Week 24 carotid MVWA; CER-001 versus placebo; measured by 3TMRI | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean vessel wall area (MVWA) of the carotid artery | Change from baseline to Week 8 carotid MVWA; CER-001 versus placebo; measured by 3TMRI | Baseline to Week 8 | 
| Change in mean vessel wall area (MVWA) of the carotid artery | Change from baseline to Week 48 carotid MVWA; CER-001 versus placebo; measured by 3TMRI | Baseline to Week 48 | 
| Change in Target to Background Ratio (TBR) of the carotid artery | Change from baseline to Week 24 in carotid TBR; CER-001 versus placebo; measured by FDG-PET | Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low HDL, Low apoA-I, ABCA-1 mutations, ApoA-I mutations