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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AEM-28 | Drug | Solution for injection |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Part A (SAD): Day 1 to Day 15; Part B (MAD): Day 1 to Day 57 |
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Inclusion Criteria:
Single Ascending Dose (SAD) Study:
Multiple Ascending Dose (MAD) Study:
Exclusion Criteria:
SAD Study:
MAD Study:
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| Name | Affiliation | Role |
|---|---|---|
| Janakan Krishnarajah, MBBS, FRACP | Linear Clinical Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Linear Clinical Research Ltd. | Nedlands | Western Australia | 6009 | Australia |
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Study conducted at Linear Clinical Research Ltd, a medical clinic in Nedlands WA Australia.
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| ID | Title | Description |
|---|---|---|
| FG000 | Apolipoprotein E Mimetic (AEM)-28 | Single Ascending Dose (SAD): Single IV dose for each cohort; dose range 0.032 mg/mL to 3.54 mg/mL Multiple Ascending Dose (MAD): Three (3) IV doses for each cohort, one (1) dose every two (2) weeks; dose range 1 mg/kg to 3.54 mg/kg. AEM-28: Solution for injection |
| FG001 | 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. Normal Saline: 0.9% saline for injection |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Single Ascending Dose |
| |||||||||||||
| Multiple Ascending Dose |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. AEM-28: Solution for injection |
| BG001 | Normal Saline |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Number | participants | Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57 |
|
Over 8 day study period for SAD study, and over 57 day study period for MAD study
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. AEM-28: Solution for injection |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Administration Site Reaction | General disorders | MedDRA 17.0 | Non-systematic Assessment | Infusion site bruising, erythema, pain, phlebitis, swelling |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Janakan Krihnarajah, MBBS (Hons), FRACP | Linear Clinical Research Ltd | 800 393 8820 | JKrishnarajah@linear.org.au |
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| ID | Term |
|---|---|
| D006937 | Hypercholesterolemia |
| D006938 | Hyperlipoproteinemia Type II |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| C000712807 | apolipoprotein E mimetic peptide CN-105 |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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| Normal Saline | Drug | 0.9% saline for injection |
|
|
| Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57 |
| NOT COMPLETED |
|
|
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. Normal Saline: 0.9% saline for injection |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | 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. Normal Saline: 0.9% saline for injection |
|
|
| Primary | 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. | Posted | Number | Number of Participants | Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57 |
|
|
|
| Primary | 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. | Posted | Number | Number of Participants | Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57 |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | Max % Change Versus Baseline | Part A (SAD): Day 1 to Day 15; Part B (MAD): Day 1 to Day 57 |
|
|
|
| 0 |
| 37 |
| 33 |
| 37 |
| EG001 | 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. Normal Saline: 0.9% saline for injection | 0 | 15 | 10 | 15 |
|
| Headache | Nervous system disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| Confusion | Injury, poisoning and procedural complications | MedDRA 17.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| Dermal Cyst | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| Infusion Related Reaction | Injury, poisoning and procedural complications | MedDRA 17.0 | Non-systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
|
| Rash Erythematous | Skin and subcutaneous tissue disorders | MedDRA 17.0 | Non-systematic Assessment |
|
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| D009750 |
| Nutritional and Metabolic Diseases |
| D008052 | Lipid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006951 | Hyperlipoproteinemias |
| Part A: 2.0 mg/kg |
|
| Part B: 2.0 mg/kg |
|
| Part A: 1.0 mg/kg |
|
| Part B: 1.0 mg/kg |
|