Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Australia

Study Type

Interventional

Intervention

AEM-28

Normal Saline

About this trial

This is an interventional treatment trial for Hypercholesterolemia focused on measuring hypercholesterolemia, apolipoprotein E, First in Human, Apolipoprotein E (ApoE), Apolipoprotein E Mimetic (AEM)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts 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.

Sites / Locations

Linear Clinical Research Ltd.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AEM-28

Normal Saline

Arm 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.

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.

Outcomes

Primary Outcome Measures

Number of Participants Who Incurred at Least One Treatment Emergent Event

Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated. Safety and tolerability data were reported using descriptive statistics.

Number of Participants Who Incurred Mild Treatment Emergent Adverse Events

Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated. Safety and tolerability data were reported using descriptive statistics.

Number of Participants Who Incurred Moderate Treatment Emergent Events

Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated. Safety and tolerability data were reported using descriptive statistics.

Secondary Outcome Measures

Very Low Density Lipoprotein Cholesterol (VLDL-C) Percent Change

Maximum observed percentage change in VLDL-C level relative to baseline for all time points measured in Parts A or Part B with highest dose, i.e. 3.54 mg/kg.

Full Information

NCT ID

NCT02100839

First Posted

March 27, 2014

Last Updated

November 23, 2015

Sponsor

LipimetiX Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT02100839

Brief Title

Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia

Official Title

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of AEM-28 in Healthy Subjects and Patients With Refractory Hypercholesterolemia

Study Type

Interventional

2. Study Status

Record Verification Date

March 2015

Overall Recruitment Status

Completed

Study Start Date

March 2014 (undefined)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

LipimetiX Development, LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypercholesterolemia, Hyperlipoproteinemia Type II

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

52 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AEM-28

Arm Type

Experimental

Arm 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.

Arm Title

Normal Saline

Arm Type

Placebo Comparator

Arm 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.

Intervention Type

Drug

Intervention Name(s)

AEM-28

Other Intervention Name(s)

apolipoprotein E mimetic

Intervention Description

Solution for injection

Intervention Type

Drug

Intervention Name(s)

Normal Saline

Other Intervention Name(s)

0.9% NaCl, Sterile Normal Saline

Intervention Description

0.9% saline for injection

Primary Outcome Measure Information:

Title

Number of Participants Who Incurred at Least One Treatment Emergent Event

Description

Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated. Safety and tolerability data were reported using descriptive statistics.

Time Frame

Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57

Title

Number of Participants Who Incurred Mild Treatment Emergent Adverse Events

Description

Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated. Safety and tolerability data were reported using descriptive statistics.

Time Frame

Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57

Title

Number of Participants Who Incurred Moderate Treatment Emergent Events

Description

Safety and tolerability to AEM-28 were evaluated through the assessment of adverse events (i.e., seriousness, severity, relationship to the study medication, outcome, duration, and management), vital signs, 12-lead ECG, telemetry, clinical laboratory parameters, physical examination, and local response to each injection, and body weight (Part B only). Treatment-emergent adverse events were tabulated by treatment. Changes from baseline values in vital signs, ECG, clinical laboratory parameters, physical examination, and body weight (Part B only) were evaluated. Safety and tolerability data were reported using descriptive statistics.

Time Frame

Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57

Secondary Outcome Measure Information:

Title

Very Low Density Lipoprotein Cholesterol (VLDL-C) Percent Change

Description

Maximum observed percentage change in VLDL-C level relative to baseline for all time points measured in Parts A or Part B with highest dose, i.e. 3.54 mg/kg.

Time Frame

Part A (SAD): Day 1 to Day 15; Part B (MAD): Day 1 to Day 57

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janakan Krishnarajah, MBBS, FRACP

Organizational Affiliation

Linear Clinical Research

Official's Role

Principal Investigator

Facility Information:

Facility Name

Linear Clinical Research Ltd.

City

Nedlands

State/Province

Western Australia

ZIP/Postal Code

6009

Country

Australia

Hypercholesterolemia, Hyperlipoproteinemia Type II

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial