Study to Investigate CSL112 in Subjects With Acute Coronary Syndrome

A Phase 3, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Investigate the Efficacy and Safety of CSL112 in Subjects With Acute Coronary Syndrome

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03473223

Acronym

AEGIS-II

Enrollment

18226

Registered

2018-03-22

Start date

2018-03-21

Completion date

2023-11-17

Last updated

2025-01-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Coronary Syndrome

Keywords

Coronary Artery Disease, Heart Disease, Cardiovascular Disease, Acute Myocardial Infarction, Heart Failure, Major adverse cardiovascular event, Multivessel disease, Peripheral artery disease, Cerebrovascular accident, Ischemic stroke, Hemorrhagic stroke, Atherosclerosis, Congestive heart failure, Valvular heart disease, Atrial Fibrillation, Hypertension

Brief summary

This is a phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group study to evaluate the efficacy and safety of CSL112 on reducing the risk of major adverse CV events \[MACE - cardiovascular (CV) death, myocardial infarction (MI), and stroke\] in subjects with acute coronary syndrome (ACS) diagnosed with either ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI), including those managed with percutaneous coronary intervention (PCI) or medically managed.

Interventions

BIOLOGICALApolipoprotein A-I [human] (apoA-I)

Apolipoprotein A-I \[human\] (apoA-I) purified from human plasma for intravenous administration

OTHERPlacebo

25% albumin solution diluted to 4.4%

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Male or female least 18 years of age * Evidence of myocardial necrosis, consistent with type I (spontaneous) MI * No suspicion of acute kidney injury * Evidence of multivessel coronary artery disease * Presence of established cardiovascular risk factor(s): 1. Diabetes mellitus on pharmacotherapy OR 2. 2 or more of the following: age ≥ 65 years, prior history of MI, peripheral arterial disease

Exclusion criteria

* Ongoing hemodynamic instability * Evidence of hepatobiliary disease * Evidence of severe chronic kidney disease * Plan to undergo scheduled coronary artery bypass graft surgery as treatment for the index MI * Known history of allergies, hypersensitivity, or deficiencies to soy bean, peanut or albumin

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With First Occurrence of Any Component of Composite MACE (CV Death, MI, or Stroke)	From the time of randomization through 90 days	MACE (Major adverse cardiovascular event\[s\])(CV \[cardiovascular\] death, MI \[Myocardial Infarction\], or stroke).

Secondary

Measure	Time frame	Description
Number of Participants With First Occurrence of CV Death, MI, or Stroke	From the time of randomization through 180 days	—
Number of Participants With Occurrence of CV Death	From the time of randomization through 90 days	—
Number of Participants With First Occurrence of MI	From the time of randomization through 90 days	—
Number of Participants With First Occurrence of Stroke	From the time of randomization through 90 days	—
Number of Participants With First Occurrence of CV Death, Type 1 MI or Stroke	From the time of randomization through 90, 180 and 365 days	—
Number of Participants With Occurrence of All-cause Death	From the time of randomization through 365 days	—
Number of Participants With Adverse Events	From the start of treatment through 90 days	An AE was defined as any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.
Percentage of Participants With Adverse Events	From the start of treatment through 90 days	An AE was defined as any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.
Number of Participants With Treatment-related Adverse Events	From the start of treatment through 379 days (Day 365 + 14 days of follow up)	Treatment-related AEs were AEs considered by the Investigator to have a causal relationship to the investigational product.
Percentage of Participants With Treatment-related Adverse Events	From the start of treatment through 379 days (Day 365 + 14 days of follow up)	Treatment-related AEs were AEs considered by the Investigator to have a causal relationship to the investigational product. As per the study statistical analysis plan (SAP), descriptive percentages were displayed to one decimal place, hence the percentage values were rounded off and presented.
Number of Participants With Serious Adverse Events (SAEs)	From the start of treatment through 379 days (Day 365 + 14 days of follow up)	SAE was defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is a medically significant event.
Total Number of Hospitalizations for Coronary, Cerebral, and Peripheral Ischemia	From the time of randomization through 90 days	The total number of hospitalizations and individual hospitalizations due to coronary, cerebral, and peripheral ischemia were reported.
Number of Participants With a Shift From Baseline to Worst Post-treatment Value in Clinical Laboratory Assessments	Baseline and 29 days	Clinical laboratory assessments included assessment of Hematology (hemoglobin, hematocrit, leukocytes and platelets) and Biochemistry (alkaline phosphatase \[ALP\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], bilirubin, direct bilirubin, indirect bilirubin and estimated glomerular filtration rate \[eGFR\]). The number of participants with a shift from the Baseline value to the worst post-treatment value (low, normal, or high) was reported. The worst criterion for the parameters is as follows: hematocrit - low, hemoglobin - low, leukocytes - high, platelets - low, ALT - high, ALP - high, AST - high, bilirubin - high, direct bilirubin - high, indirect bilirubin - high, eGFR - severe impairment.
Percentage of Participants With a Shift From Baseline to Worst Post-treatment Value in Clinical Laboratory Assessments	Baseline and 29 days	Clinical laboratory assessments included assessment of Hematology (hemoglobin, hematocrit, leukocytes and platelets) and Biochemistry (ALP, ALT, AST, bilirubin, direct bilirubin, indirect bilirubin and eGFR). Percentage of participants with a shift from the Baseline value to the worst post-treatment value (low, normal, or high) was reported. The worst criterion for the parameters is as follows: hematocrit - low, hemoglobin - low, leukocytes - high, platelets - low, ALT - high, ALP - high, AST - high, bilirubin - high, direct bilirubin - high, indirect bilirubin - high, eGFR - severe impairment. As per the study SAP, descriptive percentages were displayed to one decimal place, hence the percentage values were rounded off and presented.
Change From Baseline in Hematology Parameters	From Baseline to Day 29	Hematology parameters included Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets.
Change From Baseline in Hematology Parameter: Hematocrit	From Baseline to Day 29	—
Change From Baseline in Hematology Parameter: Hemoglobin	From Baseline to Day 29	—
Change From Baseline in Hepatic Parameters	From Baseline to Day 29	Hepatic parameters included ALT, ALP and AST.
Change From Baseline in Hepatic Parameter: Bilirubin	From Baseline to Day 29	—
Change From Baseline in Renal Parameter: Serum Creatinine	From Baseline to Day 29	—
Change From Baseline in Renal Parameter: eGFR	From Baseline to Day 29	—
Change From Baseline in Renal Parameter: Blood Urea Nitrogen	From Baseline to Day 29	—
Percentage of Participants With SAEs	From the start of treatment through 379 days (Day 365 + 14 days of follow up)	SAE was defined as any untoward medical occurrence that at any dose: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect or is a medically significant event. As per the study SAP, descriptive percentages were displayed to one decimal place, hence the percentage values were rounded off and presented.

Countries

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Czechia, Denmark, Estonia, Finland, France, Georgia, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Latvia, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Norway, Peru, Poland, Portugal, Romania, Russia, Serbia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States

Participant flow

Recruitment details

The study was conducted at 897 centers across 5 regions (North America, Latin America, Western Europe, Central and Eastern Europe, and Asia Pacific).

Pre-assignment details

A total of 18,848 participants were screened, with 622 identified as screen failures. Of the screened participants, 18,226 were randomized in a 1:1 ratio to receive study interventions (CSL112 or Placebo).

Participants by arm

Arm	Count
CSL112 Participants received 6 grams of CSL112 (apoA-I purified from human plasma) once weekly via IV infusion for up to 4 weeks.	9,112
Placebo Participants received placebo (25% albumin solution diluted to 4.4%) once weekly via IV infusion for up to 4 weeks.	9,107
Total	18,219

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Indirect contact	32	29
Overall Study	Lost to Follow-up	1	1
Overall Study	Other (Not specified)	32	20
Overall Study	Withdrawal by Subject	47	42

Baseline characteristics

Characteristic	Placebo	Total	CSL112
Age, Continuous	65.4 years STANDARD_DEVIATION 10.21	65.5 years STANDARD_DEVIATION 10.15	65.6 years STANDARD_DEVIATION 10.09
Ethnicity (NIH/OMB) Hispanic or Latino	1596 Participants	3162 Participants	1566 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7383 Participants	14793 Participants	7410 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	128 Participants	264 Participants	136 Participants
Race (NIH/OMB) American Indian or Alaska Native	36 Participants	87 Participants	51 Participants
Race (NIH/OMB) Asian	781 Participants	1524 Participants	743 Participants
Race (NIH/OMB) Black or African American	181 Participants	362 Participants	181 Participants
Race (NIH/OMB) Multiracial or other	356 Participants	670 Participants	314 Participants
Race (NIH/OMB) Native Hawaiian or other Pacific Islander	10 Participants	18 Participants	8 Participants
Race (NIH/OMB) Not Reported by subject	45 Participants	91 Participants	46 Participants
Race (NIH/OMB) White	7698 Participants	15467 Participants	7769 Participants
Sex: Female, Male Female	2386 Participants	4712 Participants	2326 Participants
Sex: Female, Male Male	6721 Participants	13507 Participants	6786 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	348 / 9,112	355 / 9,107
other Total, other adverse events	0 / 9,010	0 / 9,027
serious Total, serious adverse events	1,514 / 9,010	1,557 / 9,027

Outcome results

Primary

Number of Participants With First Occurrence of Any Component of Composite MACE (CV Death, MI, or Stroke)

MACE (Major adverse cardiovascular event\[s\])(CV \[cardiovascular\] death, MI \[Myocardial Infarction\], or stroke).

Time frame: From the time of randomization through 90 days

Population: Analysis was performed on the ITT analysis set. The ITT analysis set comprised all randomized participants with the exception of 7 participants enrolled at site(s) excluded from analysis per sponsor decision. The ITT analysis set utilized the treatment to which the participant was randomized regardless of the treatment actually received.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
CSL112	Number of Participants With First Occurrence of Any Component of Composite MACE (CV Death, MI, or Stroke)	439 Participants
Placebo	Number of Participants With First Occurrence of Any Component of Composite MACE (CV Death, MI, or Stroke)	472 Participants

p-value: 0.12195% CI: [0.8126, 1.0538]Cox proportional hazards regression

Secondary