Trial Outcomes & Findings for Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia (NCT NCT02100839)
NCT ID: NCT02100839
Last Updated: 2015-12-29
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
52 participants
Primary outcome timeframe
Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57
Results posted on
2015-12-29
Participant Flow
Study conducted at Linear Clinical Research Ltd, a medical clinic in Nedlands WA Australia.
Participant milestones
| Measure |
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
|
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
|
|---|---|---|
|
Single Ascending Dose
STARTED
|
24
|
12
|
|
Single Ascending Dose
COMPLETED
|
24
|
12
|
|
Single Ascending Dose
NOT COMPLETED
|
0
|
0
|
|
Multiple Ascending Dose
STARTED
|
13
|
3
|
|
Multiple Ascending Dose
COMPLETED
|
9
|
3
|
|
Multiple Ascending Dose
NOT COMPLETED
|
4
|
0
|
Reasons for withdrawal
| Measure |
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
|
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
|
|---|---|---|
|
Multiple Ascending Dose
Adverse Event
|
2
|
0
|
|
Multiple Ascending Dose
Withdrawal by Subject
|
2
|
0
|
Baseline Characteristics
Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia
Baseline characteristics by cohort
| Measure |
AEM-28
n=37 Participants
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
|
Normal Saline
n=15 Participants
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
|
Total
n=52 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
35 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Continuous
|
35.7 years
n=5 Participants
|
32 years
n=7 Participants
|
34.6 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
33 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
31 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
37 participants
n=5 Participants
|
15 participants
n=7 Participants
|
52 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57Safety 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.
Outcome measures
| Measure |
AEM-28
n=37 Participants
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
|
Normal Saline
n=15 Participants
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
|
|---|---|---|
|
Number of Participants Who Incurred at Least One Treatment Emergent Event
|
33 participants
|
10 participants
|
PRIMARY outcome
Timeframe: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57Safety 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.
Outcome measures
| Measure |
AEM-28
n=37 Participants
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
|
Normal Saline
n=15 Participants
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
|
|---|---|---|
|
Number of Participants Who Incurred Mild Treatment Emergent Adverse Events
|
33 Number of Participants
|
10 Number of Participants
|
PRIMARY outcome
Timeframe: Part A (SAD): Day -1 to Day 15; Part B (MAD): Day 1 to Day 57Safety 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.
Outcome measures
| Measure |
AEM-28
n=37 Participants
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
|
Normal Saline
n=15 Participants
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
|
|---|---|---|
|
Number of Participants Who Incurred Moderate Treatment Emergent Events
|
7 Number of Participants
|
0 Number of Participants
|
SECONDARY outcome
Timeframe: Part A (SAD): Day 1 to Day 15; Part B (MAD): Day 1 to Day 57Maximum 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.
Outcome measures
| Measure |
AEM-28
n=37 Participants
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
|
Normal Saline
n=15 Participants
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
|
|---|---|---|
|
Very Low Density Lipoprotein Cholesterol (VLDL-C) Percent Change
Part A: 3.54 mg/kg
|
-72.1 Max % Change Versus Baseline
Standard Deviation 15.1
|
-0.33 Max % Change Versus Baseline
Standard Deviation 0.17
|
|
Very Low Density Lipoprotein Cholesterol (VLDL-C) Percent Change
Part B: 3.54 mg/kg
|
-79.2 Max % Change Versus Baseline
Standard Deviation 13.5
|
-0.58 Max % Change Versus Baseline
Standard Deviation 0.31
|
|
Very Low Density Lipoprotein Cholesterol (VLDL-C) Percent Change
Part A: 2.0 mg/kg
|
-76.3 Max % Change Versus Baseline
Standard Deviation 7.25
|
-0.35 Max % Change Versus Baseline
Standard Deviation 0.13
|
|
Very Low Density Lipoprotein Cholesterol (VLDL-C) Percent Change
Part B: 2.0 mg/kg
|
-73.3 Max % Change Versus Baseline
Standard Deviation 6.36
|
-0.52 Max % Change Versus Baseline
Standard Deviation 0.15
|
|
Very Low Density Lipoprotein Cholesterol (VLDL-C) Percent Change
Part A: 1.0 mg/kg
|
-47.9 Max % Change Versus Baseline
Standard Deviation 19.7
|
-0.23 Max % Change Versus Baseline
Standard Deviation 0.15
|
|
Very Low Density Lipoprotein Cholesterol (VLDL-C) Percent Change
Part B: 1.0 mg/kg
|
-51.8 Max % Change Versus Baseline
Standard Deviation 24.7
|
-0.38 Max % Change Versus Baseline
Standard Deviation 0.19
|
Adverse Events
AEM-28
Serious events: 0 serious events
Other events: 33 other events
Deaths: 0 deaths
Normal Saline
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
AEM-28
n=37 participants at risk
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
|
Normal Saline
n=15 participants at risk
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
|
|---|---|---|
|
General disorders
Administration Site Reaction
|
78.4%
29/37 • Number of events 46 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
40.0%
6/15 • Number of events 7 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
|
Nervous system disorders
Headache
|
24.3%
9/37 • Number of events 12 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
0.00%
0/15 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
|
Injury, poisoning and procedural complications
Confusion
|
5.4%
2/37 • Number of events 2 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
13.3%
2/15 • Number of events 2 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
|
General disorders
Fatigue
|
2.7%
1/37 • Number of events 1 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
13.3%
2/15 • Number of events 2 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
|
Cardiac disorders
Palpitations
|
2.7%
1/37 • Number of events 1 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
6.7%
1/15 • Number of events 1 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
|
Nervous system disorders
Somnolence
|
0.00%
0/37 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
6.7%
1/15 • Number of events 1 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/37 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
6.7%
1/15 • Number of events 1 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
5.4%
2/37 • Number of events 2 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
6.7%
1/15 • Number of events 1 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
|
Skin and subcutaneous tissue disorders
Dermal Cyst
|
0.00%
0/37 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
6.7%
1/15 • Number of events 1 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
|
Gastrointestinal disorders
Nausea
|
2.7%
1/37 • Number of events 1 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
6.7%
1/15 • Number of events 1 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
|
Injury, poisoning and procedural complications
Infusion Related Reaction
|
16.2%
6/37 • Number of events 13 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
6.7%
1/15 • Number of events 1 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/37 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
6.7%
1/15 • Number of events 1 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
|
Skin and subcutaneous tissue disorders
Rash Erythematous
|
0.00%
0/37 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
6.7%
1/15 • Number of events 1 • Over 8 day study period for SAD study, and over 57 day study period for MAD study
|
Additional Information
Dr. Janakan Krihnarajah, MBBS (Hons), FRACP
Linear Clinical Research Ltd
Phone: 800 393 8820
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place