Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia

NCT ID: NCT02100839

Last Updated: 2015-12-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2014-12-31

Brief Summary

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.

Conditions

Hypercholesterolemia; Hyperlipoproteinemia Type II

Keywords

hypercholesterolemia; apolipoprotein E; First in Human; Apolipoprotein E (ApoE); Apolipoprotein E Mimetic (AEM)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

AEM-28

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.

Group Type: EXPERIMENTAL

AEM-28

Intervention Type: DRUG

Solution for injection

Normal Saline

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.

Group Type: PLACEBO_COMPARATOR

Normal Saline

Intervention Type: DRUG

0.9% saline for injection

Interventions

AEM-28

Solution for injection

Intervention Type: DRUG

Normal Saline

0.9% saline for injection

Intervention Type: DRUG

Other Intervention Names

apolipoprotein E mimetic; 0.9% NaCl; Sterile Normal Saline

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

LipimetiX Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janakan Krishnarajah, MBBS, FRACP

Role: PRINCIPAL_INVESTIGATOR

Linear Clinical Research

Locations

Linear Clinical Research Ltd.

Nedlands, Western Australia, Australia

Countries

Australia

Other Identifiers

LPMX-112

Identifier Type: -

Identifier Source: org_study_id