Trial Outcomes & Findings for A Study of CSL112 in Adults With Moderate Renal Impairment and Acute Myocardial Infarction (NCT NCT02742103)
NCT ID: NCT02742103
Last Updated: 2020-06-11
Results Overview
A renal SAE is defined as any SAE with a MedDRA preferred term included in the Acute Renal Failure narrow Standard MedDRA Query or a preferred term of renal tubular necrosis, renal cortical necrosis, renal necrosis, or renal papillary necrosis.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
83 participants
Primary outcome timeframe
Up to 9 weeks
Results posted on
2020-06-11
Participant Flow
To ensure that at least 1/3 of the study population had an estimated glomerular filtration (eGFR) in the chronic kidney disease (CKD) Stage 3b range, no more than 2/3 of the study population were to have an eGFR in the CKD Stage 3a range. Randomization was stratified by eGFR and by medical history of diabetes.
Participant milestones
| Measure |
CSL_112
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Overall Study
STARTED
|
55
|
28
|
|
Overall Study
COMPLETED
|
46
|
23
|
|
Overall Study
NOT COMPLETED
|
9
|
5
|
Reasons for withdrawal
| Measure |
CSL_112
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Death
|
2
|
2
|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Moved to another town
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
5
|
2
|
Baseline Characteristics
A Study of CSL112 in Adults With Moderate Renal Impairment and Acute Myocardial Infarction
Baseline characteristics by cohort
| Measure |
CSL_112
n=55 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
Total
n=83 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
70.6 years
STANDARD_DEVIATION 10.95 • n=5 Participants
|
71.9 years
STANDARD_DEVIATION 10.12 • n=7 Participants
|
71.1 years
STANDARD_DEVIATION 10.63 • n=5 Participants
|
|
Age, Customized
18-64 years
|
11 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Age, Customized
65-84 years
|
42 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
65 Participants
n=5 Participants
|
|
Age, Customized
85 years and over
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
55 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
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 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
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
52 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
80 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
8 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
20 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
12 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 9 weeksPopulation: The Safety (SAF) Population consisted of all subjects who received at least a partial dose of investigational product.
A renal SAE is defined as any SAE with a MedDRA preferred term included in the Acute Renal Failure narrow Standard MedDRA Query or a preferred term of renal tubular necrosis, renal cortical necrosis, renal necrosis, or renal papillary necrosis.
Outcome measures
| Measure |
CSL_112
n=52 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Percent of Participants With at Least One Occurrence of Treatment-emergent Renal Serious Adverse Events (SAEs) (SAF)
|
1.9 percentage of participants
|
14.3 percentage of participants
|
PRIMARY outcome
Timeframe: Up to 4 weeksPopulation: SAF
Acute kidney injury is defined as an absolute increase in serum creatinine from baseline ≥ 0.3 mg/dL during the Active Treatment Period that is sustained upon repeat measurement by the central laboratory no earlier than 24 hours after the elevated value. If no repeat value is obtained, a single serum creatinine value that is increased from baseline ≥ 0.3 mg/dL (26.5 μmol/L) during the Active Treatment Period would also fulfil the definition of AKI.
Outcome measures
| Measure |
CSL_112
n=50 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Percent of Participants With Treatment-emergent Acute Kidney Injury (AKI )
|
4.0 percentage of participants
|
14.3 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 9 weeksPopulation: SAF
Outcome measures
| Measure |
CSL_112
n=52 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
|
38 participants
|
20 participants
|
SECONDARY outcome
Timeframe: Up to 9 weeksPopulation: SAF
Outcome measures
| Measure |
CSL_112
n=52 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Percentage of Participants With TEAEs
|
73.1 percentage of participants
|
71.4 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 9 weeksPopulation: SAF
Outcome measures
| Measure |
CSL_112
n=52 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Total Number of TEAEs
|
111 Number of TEAEs
|
61 Number of TEAEs
|
SECONDARY outcome
Timeframe: Up to 9 weeksPopulation: SAF
Adverse drug reactions or suspected adverse drug reactions are defined as: 1. All TEAEs, including local tolerability events, that begin during or within 1 hour after the end of an infusion; or 2. Those TEAEs that the investigator or sponsor indicate may be causally related to product administration; or 3. All TEAEs for which the Investigator's causality assessment is missing or indeterminate; or 4. All TEAEs for which the incidence in an active treatment arm exceeds the exposure-adjusted incidence rate in the placebo arm by 30% or more, provided the difference in incidence rates is 1% or more.
Outcome measures
| Measure |
CSL_112
n=52 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR
|
30 participants
|
4 participants
|
SECONDARY outcome
Timeframe: Up to 9 weeksPopulation: SAF
Adverse drug reactions or suspected adverse drug reactions are defined as: 1. All TEAEs, including local tolerability events, that begin during or within 1 hour after the end of an infusion; or 2. Those TEAEs that the investigator or sponsor indicate may be causally related to product administration; or 3. All TEAEs for which the Investigator's causality assessment is missing or indeterminate; or 4. All TEAEs for which the incidence in an active treatment arm exceeds the exposure-adjusted incidence rate in the placebo arm by 30% or more, provided the difference in incidence rates is 1% or more.
Outcome measures
| Measure |
CSL_112
n=52 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Percentage of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR
|
57.7 percentage of participants
|
14.3 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and up to 4 weeksPopulation: SAF
Number of participants with changes in renal status defined as: * Absolute increases from baseline in serum creatinine as follows: i. ≤ baseline value ii. \> 0 to \< 0.3 mg/dL iii. ≥ 0.3 to ≤ 0.5 mg/dL iv. \> 0.5 mg/dL * Increases in serum creatinine that are sustained for ≥ 24 hours upon repeat measurement that are greater than or equal to 1.5 x, 2 x, or 3.0 x the baseline value, or serum creatinine ≥ 4.0 mg/dL * Initiation of renal replacement therapy * Decrease in eGFR ≥ 25% from baseline starting during the active treatment period and that is sustained at the final study visit
Outcome measures
| Measure |
CSL_112
n=52 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Number of Participants With Change in Renal Status
≥ 3 × Baseline
|
0 participants
|
0 participants
|
|
Number of Participants With Change in Renal Status
≥ 4.0 mg/dL
|
0 participants
|
0 participants
|
|
Number of Participants With Change in Renal Status
Decrease in eGFR by ≥ 25%
|
5 participants
|
4 participants
|
|
Number of Participants With Change in Renal Status
≤ baseline value
|
9 participants
|
3 participants
|
|
Number of Participants With Change in Renal Status
> 0 to < 0.3 mg/dL
|
35 participants
|
18 participants
|
|
Number of Participants With Change in Renal Status
≥ 0.3 to ≤ 0.5 mg/dL
|
4 participants
|
4 participants
|
|
Number of Participants With Change in Renal Status
> 0.5 mg/dL
|
2 participants
|
2 participants
|
|
Number of Participants With Change in Renal Status
≥ 1.5 × Baseline
|
1 participants
|
0 participants
|
|
Number of Participants With Change in Renal Status
≥ 2 × Baseline
|
0 participants
|
0 participants
|
|
Number of Participants With Change in Renal Status
Initiation of renal replacement therapy
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline and up to 4 weeksPopulation: SAF
Percentage of participants with changes in renal status defined as: * Absolute increases from baseline in serum creatinine as follows: i. ≤ baseline value ii. \> 0 to \< 0.3 mg/dL iii. ≥ 0.3 to ≤ 0.5 mg/dL iv. \> 0.5 mg/dL * Increases in serum creatinine that are sustained for ≥ 24 hours upon repeat measurement that are greater than or equal to 1.5 x, 2 x, or 3.0 x the baseline value, or serum creatinine ≥ 4.0 mg/dL * Initiation of renal replacement therapy * Decrease in eGFR ≥ 25% from baseline starting during the active treatment period and that is sustained at the final study visit
Outcome measures
| Measure |
CSL_112
n=52 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Percentage of Participants With Change in Renal Status
≤ Baseline Value
|
17.3 percentage of participants
|
10.7 percentage of participants
|
|
Percentage of Participants With Change in Renal Status
> 0 to < 0.3 mg/dL
|
67.3 percentage of participants
|
64.3 percentage of participants
|
|
Percentage of Participants With Change in Renal Status
≥ 0.3 to ≤ 0.5 mg/dL
|
7.7 percentage of participants
|
14.3 percentage of participants
|
|
Percentage of Participants With Change in Renal Status
> 0.5 mg/dL
|
3.8 percentage of participants
|
7.1 percentage of participants
|
|
Percentage of Participants With Change in Renal Status
≥ 1.5 × Baseline
|
1.9 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Change in Renal Status
≥ 2 × Baseline
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Change in Renal Status
≥ 3 × Baseline
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Change in Renal Status
≥ 4.0 mg/dL
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Change in Renal Status
Decrease in eGFR by ≥ 25%
|
9.6 percentage of participants
|
14.3 percentage of participants
|
|
Percentage of Participants With Change in Renal Status
Initiation of renal replacement therapy
|
0 percentage of participants
|
3.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and up to 4 weeksPopulation: SAF
Number of participants with a change from baseline in hepatic status and that is sustained for ≥ 24 hours upon repeat measurement, defined as: 1. Alanine aminotransferase (ALT) \> 3 x upper limit of normal (ULN) 2. ALT \> 5 x ULN 3. ALT \> 10 x ULN 4. Serum total bilirubin \> 1.5 x ULN 5. Serum total bilirubin \> 2 x ULN 6. Possible Hy's law cases, as defined in the FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation (July 2009).
Outcome measures
| Measure |
CSL_112
n=52 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Number of Participants With Change in Hepatic Status
total bilirubin > 1.5 x ULN
|
4 participants
|
1 participants
|
|
Number of Participants With Change in Hepatic Status
total bilirubin > 2 x ULN
|
1 participants
|
0 participants
|
|
Number of Participants With Change in Hepatic Status
ALT > 3 x ULN
|
0 participants
|
0 participants
|
|
Number of Participants With Change in Hepatic Status
ALT > 5 x ULN
|
0 participants
|
0 participants
|
|
Number of Participants With Change in Hepatic Status
ALT > 10 x ULN
|
0 participants
|
0 participants
|
|
Number of Participants With Change in Hepatic Status
Possible Hy's law cases
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline and up to 4 weeksPopulation: SAF
Percentage of participants with a change from baseline in hepatic status and that is sustained for ≥ 24 hours upon repeat measurement, defined as: 1. Alanine aminotransferase (ALT) \> 3 x upper limit of normal (ULN) 2. ALT \> 5 x ULN 3. ALT \> 10 x ULN 4. Serum total bilirubin \> 1.5 x ULN 5. Serum total bilirubin \> 2 x ULN 6. Possible Hy's law cases, as defined in the FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation (July 2009).
Outcome measures
| Measure |
CSL_112
n=52 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Percentage of Participants With Change in Hepatic Status
total bilirubin > 1.5 x ULN
|
7.7 percentage of participants
|
3.7 percentage of participants
|
|
Percentage of Participants With Change in Hepatic Status
total bilirubin > 2 x ULN
|
1.9 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Change in Hepatic Status
ALT > 3 x ULN
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Change in Hepatic Status
ALT > 5 x ULN
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Change in Hepatic Status
ALT > 10 x ULN
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Change in Hepatic Status
Possible Hy's law cases
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 9 weeksPopulation: SAF
Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).
Outcome measures
| Measure |
CSL_112
n=52 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Number of Participants With Treatment-emergent Bleeding Events
|
7 participants
|
5 participants
|
SECONDARY outcome
Timeframe: Up to 9 weeksPopulation: SAF
Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).
Outcome measures
| Measure |
CSL_112
n=52 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Percentage of Participants With Treatment-emergent Bleeding Events
|
13.5 percentage of participants
|
17.9 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 9 weeksPopulation: SAF
Outcome measures
| Measure |
CSL_112
n=52 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Percentage of Participants With Binding Antibodies Specific to Apolipoprotein A-I (Apo-A1) and CSL112
CSL112 antibody
|
0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Binding Antibodies Specific to Apolipoprotein A-I (Apo-A1) and CSL112
apoA-I antibody
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Immediately after end of infusionPopulation: PK
Outcome measures
| Measure |
CSL_112
n=52 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 1 for apoA-I and PC
apoA-I
|
124.6 mg/dL
Standard Deviation 25.38
|
-4.5 mg/dL
Standard Deviation 9.46
|
|
Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 1 for apoA-I and PC
PC
|
198.4 mg/dL
Standard Deviation 43.56
|
-4.9 mg/dL
Standard Deviation 15.04
|
SECONDARY outcome
Timeframe: Immediately after end of infusionPopulation: PK
Outcome measures
| Measure |
CSL_112
n=38 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=21 Participants
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 4 for apoA-I and PC
apoA-I
|
141.5 mg/dL
Standard Deviation 41.11
|
1.4 mg/dL
Standard Deviation 23.57
|
|
Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 4 for apoA-I and PC
PC
|
200.0 mg/dL
Standard Deviation 71.78
|
-13.2 mg/dL
Standard Deviation 27.96
|
SECONDARY outcome
Timeframe: Immediately after end of infusionPopulation: Pharmacokinetic Population (PK) consists of all subjects in the SAF who had at least 1 measurable plasma concentration of either apoA-I or PC.
The plasma apoA-I and PC accumulation ratio will be determined for CSL112-treated subjects.
Outcome measures
| Measure |
CSL_112
n=38 Participants
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Plasma apoA-I and Phosphatidylcholine (PC) Accumulation Ratio After Infusion 4
apoA-I
|
1.2 mg/dL
Standard Deviation 0.32
|
—
|
|
Plasma apoA-I and Phosphatidylcholine (PC) Accumulation Ratio After Infusion 4
PC
|
1.0 mg/dL
Standard Deviation 0.36
|
—
|
Adverse Events
CSL_112
Serious events: 12 serious events
Other events: 18 other events
Deaths: 2 deaths
Placebo
Serious events: 10 serious events
Other events: 12 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
CSL_112
n=52 participants at risk
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 participants at risk
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Vascular disorders
Hypertension
|
0.00%
0/52 • 67 days for each subject
|
3.6%
1/28 • Number of events 1 • 67 days for each subject
|
|
Injury, poisoning and procedural complications
Post concussion syndrome
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/52 • 67 days for each subject
|
3.6%
1/28 • Number of events 1 • 67 days for each subject
|
|
Cardiac disorders
Atrial fibrillation
|
5.8%
3/52 • Number of events 3 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
Cardiac disorders
Cardiac failure
|
5.8%
3/52 • Number of events 3 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
Cardiac disorders
Acute coronary syndrome
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
Cardiac disorders
Acute myocardial infarction
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
3.6%
1/28 • Number of events 1 • 67 days for each subject
|
|
Cardiac disorders
Angina unstable
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
3.6%
1/28 • Number of events 1 • 67 days for each subject
|
|
Cardiac disorders
Cardiac failure acute
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
Cardiac disorders
Sinus node dysfunction
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/52 • 67 days for each subject
|
7.1%
2/28 • Number of events 2 • 67 days for each subject
|
|
Blood and lymphatic system disorders
Microcytic anaemia
|
0.00%
0/52 • 67 days for each subject
|
3.6%
1/28 • Number of events 1 • 67 days for each subject
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/52 • 67 days for each subject
|
3.6%
1/28 • Number of events 1 • 67 days for each subject
|
|
Nervous system disorders
Ataxia
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
Nervous system disorders
Syncope
|
0.00%
0/52 • 67 days for each subject
|
3.6%
1/28 • Number of events 1 • 67 days for each subject
|
|
Eye disorders
Visual impairment
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
General disorders
Death
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
3.6%
1/28 • Number of events 1 • 67 days for each subject
|
|
Ear and labyrinth disorders
Vestibular disorder
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
Gastrointestinal disorders
Gastrointestinal erosion
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
Renal and urinary disorders
Nephropathy toxic
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/52 • 67 days for each subject
|
7.1%
2/28 • Number of events 2 • 67 days for each subject
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/52 • 67 days for each subject
|
3.6%
1/28 • Number of events 2 • 67 days for each subject
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/52 • 67 days for each subject
|
3.6%
1/28 • Number of events 1 • 67 days for each subject
|
|
Infections and infestations
Urinary tract infection
|
1.9%
1/52 • Number of events 1 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
Infections and infestations
Bronchitis
|
0.00%
0/52 • 67 days for each subject
|
3.6%
1/28 • Number of events 1 • 67 days for each subject
|
|
Infections and infestations
Pneumonia
|
0.00%
0/52 • 67 days for each subject
|
3.6%
1/28 • Number of events 1 • 67 days for each subject
|
Other adverse events
| Measure |
CSL_112
n=52 participants at risk
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
CSL\_112: CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
|
Placebo
n=28 participants at risk
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Placebo: 0.9% weight/volume sodium chloride solution (ie, normal saline)
|
|---|---|---|
|
Vascular disorders
Hypertension
|
9.6%
5/52 • Number of events 5 • 67 days for each subject
|
3.6%
1/28 • Number of events 1 • 67 days for each subject
|
|
Investigations
Blood creatinine increased
|
9.6%
5/52 • Number of events 5 • 67 days for each subject
|
0.00%
0/28 • 67 days for each subject
|
|
Investigations
Haemoglobin decreased
|
5.8%
3/52 • Number of events 3 • 67 days for each subject
|
7.1%
2/28 • Number of events 2 • 67 days for each subject
|
|
Cardiac disorders
Angina pectoris
|
9.6%
5/52 • Number of events 5 • 67 days for each subject
|
7.1%
2/28 • Number of events 2 • 67 days for each subject
|
|
Vascular disorders
Hypotension
|
0.00%
0/52 • 67 days for each subject
|
7.1%
2/28 • Number of events 2 • 67 days for each subject
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/52 • 67 days for each subject
|
7.1%
2/28 • Number of events 3 • 67 days for each subject
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/52 • 67 days for each subject
|
10.7%
3/28 • Number of events 3 • 67 days for each subject
|
|
Gastrointestinal disorders
Diarrhoea
|
7.7%
4/52 • Number of events 4 • 67 days for each subject
|
3.6%
1/28 • Number of events 1 • 67 days for each subject
|
|
Gastrointestinal disorders
Nausea
|
3.8%
2/52 • Number of events 2 • 67 days for each subject
|
7.1%
2/28 • Number of events 2 • 67 days for each subject
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/52 • 67 days for each subject
|
7.1%
2/28 • Number of events 2 • 67 days for each subject
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place