Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia

LipimetiX Development

Status and phase: Completed; Phase 2; Phase 1

Conditions: Hyperlipoproteinemia Type II; Hypercholesterolemia

Treatments: Drug: AEM-28; Drug: Normal Saline

Study type: Interventional

Funder types: Industry

Identifiers

NCT02100839

LPMX-112

Details and patient eligibility

About

The purpose of the first part of this study is to determine the safety and tolerability of a single dose of AEM-28, an apolipoprotein E mimetic, in subjects with high total cholesterol who are otherwise healthy subjects. The pharmacokinetics and pharmacodynamics of AEM-28 will also be evaluated.

The second part of this study will be a multiple ascending dose evaluation of AEM-28 in patients with refractory hypercholesterolemia.

AEM-28 has demonstrated significant lipid lowering activity and positive effects on the artery wall. AEM-28 is being developed for the treatment of homozygous familial hypercholesterolemia.

Enrollment: 52 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Single Ascending Dose (SAD) Study:

• Male or female non-smoker, ≥18 and ≤55 years of age, with BMI >18.5 and < 32.0 kg/m²
• Total cholesterol greater or equal to 5.0 mmol/L (≥194 mg/dL) at screening

Multiple Ascending Dose (MAD) Study:

• Male or female non-smoker, ≥18 and ≤75 years of age, with BMI >18.5 and < 35.0 kg/m²
• Diagnosis of refractory hypercholesterolemia with LDL cholesterol levels > 2.5 mmol/L (97 mg/mL) at screening.
• On stable lipid lowering therapy for ≥ 8 weeks
• On stable diet for ≥ 12 weeks.

Exclusion criteria

SAD Study:

• Any clinically significant abnormality or abnormal laboratory test results found during medical screening or positive test for hepatitis B, hepatitis C, or HIV found during medical screening.
• History of allergic reactions to diphenhydramine, ranitidine, methylprednisone or other related drugs, or history of significant allergic or hypersensitivity reaction (e.g. angioedema) to any substance.

MAD Study:

• Significant health problems within 6 months prior to screening, which in the opinion of the Medical Sub-Investigator would prevent the subject from participating in the study, including but not limited to: unstable coronary heart disease; transient ischemic attack; stroke; revascularization procedure; uncontrolled hyperthyroidism; coagulation disorder; peptic ulcers or GI bleeding; significant disease of the central nervous system; liver or renal disease.
• History of allergic reactions to diphenhydramine, ranitidine, methylprednisone or other related drugs, or history of significant allergic or hypersensitivity reaction (e.g. angioedema) to any substance.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Quadruple Blind

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52 participants in 2 patient groups, including a placebo group

AEM-28

Experimental group

Description:

Single Ascending Dose: Single IV dose for each cohort; dose range 0.032 mg/mL to 3.54 mg/mL Multiple Ascending Dose: Three (3) IV doses for each cohort, one (1) dose every two (2) weeks; dose range 1 mg/kg to 3.54 mg/kg.

Treatment:

Drug: AEM-28

Normal Saline

Placebo Comparator group

Description:

Single Ascending Dose: Single IV dose for each cohort. Multiple Ascending Dose: Three (3) IV doses for each cohort, one (1) dose every two (2) weeks.

Treatment:

Drug: Normal Saline