Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia

NCT02100839 | Completed Phase 1 Results DMC

• 1 other identifier: LPMX-112
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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)

Outcome Measures

Primary Outcomes (3)

• 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.

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

• 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.

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

• 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.

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

Secondary Outcomes (1)

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

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

Study Arms (2)

AEM-28

EXPERIMENTAL

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.

Drug: AEM-28

Normal Saline

PLACEBO COMPARATOR

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.

Drug: Normal Saline

Interventions

AEM-28 DRUG

Solution for injection

Also known as: apolipoprotein E mimetic

AEM-28

Normal Saline DRUG

0.9% saline for injection

Also known as: 0.9% NaCl, Sterile Normal Saline

Normal Saline

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• LipimetiX Development, LLC: lead

Study Sites (1)

Linear Clinical Research Ltd.

Nedlands, Western Australia, 6009, Australia

Location

MeSH Terms

Conditions

Hypercholesterolemia; Hyperlipoproteinemia Type II

Interventions

apolipoprotein E mimetic peptide CN-105; Saline Solution

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Janakan Krihnarajah, MBBS (Hons), FRACP
• Organization: Linear Clinical Research Ltd

JKrishnarajah@linear.org.au

800 393 8820

Study Officials

• Janakan Krishnarajah, MBBS, FRACP

  Linear Clinical Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2014
• First Posted: April 1, 2014
• Study Start: March 1, 2014
• Primary Completion: November 1, 2014
• Study Completion: December 1, 2014
• Last Updated: December 29, 2015
• Results First Posted: December 29, 2015

Record last verified: 2015-03

Locations

AU (1)