Back to resultsA Study of CSL112 in Adults With Moderate Renal Impairment and Acute Myocardial Infarction
Primary Purpose
Acute Myocardial Infarction, Moderate Renal Impairment
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
CSL_112
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Acute Myocardial Infarction
Eligibility Criteria
Inclusion Criteria:
• Men or women, at least 18 years of age, with evidence of moderate renal impairment (an eGFR ≥ 30 and <60 mL/min/1.73 m2) and myocardial necrosis in a clinical setting consistent with a type I (spontaneous) acute myocardial infarction (AMI).
Exclusion Criteria:
- Symptoms, biomarker elevation or electrocardiogram (ECG) changes other than those of the index event that are consistent with a diagnosis of AMI but are likely not due to primary myocardial ischemia
- Ongoing hemodynamic instability
- Planned coronary artery bypass surgery
- Evidence of hepatobiliary disease
- History of acute kidney injury (AKI) after previous exposure to an intravenous contrast agent.
- History of nephrotic range proteinuria.
- Known history of allergy to soy beans or peanuts, immunoglobulin A (IgA) deficiency, antibodies to IgA , or hypersensitivity to CSL112 or any of its components.
- Other severe comorbid condition, concurrent medication, or other issue that renders the subject unsuitable for participation in the study.
Sites / Locations
- Study Site 16101
- Study Site 16078
- Study Site 16168
- Study Site 16130
- Study Site 16135
- Study Site 16003
- Study Site 16112
- Study Site 16208
- Study Site 16061
- Study Site 16056
- Study Site 16014
- Study Site 16018
- Study Site 16241
- Study Site 17001
- Study Site 17014
- Study Site 17005
- Study Site 17009
- Study Site 17003
- Study Site 17006
- Study Site 18001
- Study Site 18005
- Study Site 18007
- Study Site 18003
- Study Site 18009
- Study Site 19005
- Study Site 19002
- Study Site 19008
- Study Site 21001
- Study Site 21006
- Study Site 21017
- Study Site 21008
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
CSL_112
Placebo
Arm Description
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Outcomes
Primary Outcome Measures
Percent of Participants With at Least One Occurrence of Treatment-emergent Renal Serious Adverse Events (SAEs) (SAF)
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.
Percent of Participants With Treatment-emergent Acute Kidney Injury (AKI )
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.
Secondary Outcome Measures
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Percentage of Participants With TEAEs
Total Number of TEAEs
Number of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR
Adverse drug reactions or suspected adverse drug reactions are defined as:
All TEAEs, including local tolerability events, that begin during or within 1 hour after the end of an infusion; or
Those TEAEs that the investigator or sponsor indicate may be causally related to product administration; or
All TEAEs for which the Investigator's causality assessment is missing or indeterminate; or
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.
Percentage of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR
Adverse drug reactions or suspected adverse drug reactions are defined as:
All TEAEs, including local tolerability events, that begin during or within 1 hour after the end of an infusion; or
Those TEAEs that the investigator or sponsor indicate may be causally related to product administration; or
All TEAEs for which the Investigator's causality assessment is missing or indeterminate; or
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.
Number of Participants With Change in Renal Status
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
Percentage of Participants With Change in Renal Status
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
Number of Participants With Change in Hepatic Status
Number of participants with a change from baseline in hepatic status and that is sustained for ≥ 24 hours upon repeat measurement, defined as:
Alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
ALT > 5 x ULN
ALT > 10 x ULN
Serum total bilirubin > 1.5 x ULN
Serum total bilirubin > 2 x ULN
Possible Hy's law cases, as defined in the FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation (July 2009).
Percentage of Participants With Change in Hepatic Status
Percentage of participants with a change from baseline in hepatic status and that is sustained for ≥ 24 hours upon repeat measurement, defined as:
Alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
ALT > 5 x ULN
ALT > 10 x ULN
Serum total bilirubin > 1.5 x ULN
Serum total bilirubin > 2 x ULN
Possible Hy's law cases, as defined in the FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation (July 2009).
Number of Participants With Treatment-emergent Bleeding Events
Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).
Percentage of Participants With Treatment-emergent Bleeding Events
Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).
Percentage of Participants With Binding Antibodies Specific to Apolipoprotein A-I (Apo-A1) and CSL112
Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 1 for apoA-I and PC
Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 4 for apoA-I and PC
Plasma apoA-I and Phosphatidylcholine (PC) Accumulation Ratio After Infusion 4
The plasma apoA-I and PC accumulation ratio will be determined for CSL112-treated subjects.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02742103
Brief Title
A Study of CSL112 in Adults With Moderate Renal Impairment and Acute Myocardial Infarction
Official Title
A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group, Study to Investigate the Safety and Tolerability of Multiple Dose Administration of CSL112 in Subjects With Moderate Renal Impairment and Acute Myocardial Infarction
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
August 2016 (undefined)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
June 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is a phase 2, multicenter, double-blind, randomized, placebo controlled, parallel-group study to investigate the renal safety and tolerability of multiple dose intravenous (IV) administration of CSL112 compared with placebo in subjects with moderate renal impairment (RI) and acute myocardial infarction (AMI).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myocardial Infarction, Moderate Renal Impairment
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
83 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CSL_112
Arm Type
Experimental
Arm Description
CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Intervention Type
Biological
Intervention Name(s)
CSL_112
Intervention Description
CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
0.9% weight/volume sodium chloride solution (ie, normal saline)
Primary Outcome Measure Information:
Title
Percent of Participants With at Least One Occurrence of Treatment-emergent Renal Serious Adverse Events (SAEs) (SAF)
Description
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.
Time Frame
Up to 9 weeks
Title
Percent of Participants With Treatment-emergent Acute Kidney Injury (AKI )
Description
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.
Time Frame
Up to 4 weeks
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time Frame
Up to 9 weeks
Title
Percentage of Participants With TEAEs
Time Frame
Up to 9 weeks
Title
Total Number of TEAEs
Time Frame
Up to 9 weeks
Title
Number of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR
Description
Adverse drug reactions or suspected adverse drug reactions are defined as:
All TEAEs, including local tolerability events, that begin during or within 1 hour after the end of an infusion; or
Those TEAEs that the investigator or sponsor indicate may be causally related to product administration; or
All TEAEs for which the Investigator's causality assessment is missing or indeterminate; or
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.
Time Frame
Up to 9 weeks
Title
Percentage of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR
Description
Adverse drug reactions or suspected adverse drug reactions are defined as:
All TEAEs, including local tolerability events, that begin during or within 1 hour after the end of an infusion; or
Those TEAEs that the investigator or sponsor indicate may be causally related to product administration; or
All TEAEs for which the Investigator's causality assessment is missing or indeterminate; or
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.
Time Frame
Up to 9 weeks
Title
Number of Participants With Change in Renal Status
Description
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
Time Frame
Baseline and up to 4 weeks
Title
Percentage of Participants With Change in Renal Status
Description
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
Time Frame
Baseline and up to 4 weeks
Title
Number of Participants With Change in Hepatic Status
Description
Number of participants with a change from baseline in hepatic status and that is sustained for ≥ 24 hours upon repeat measurement, defined as:
Alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
ALT > 5 x ULN
ALT > 10 x ULN
Serum total bilirubin > 1.5 x ULN
Serum total bilirubin > 2 x ULN
Possible Hy's law cases, as defined in the FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation (July 2009).
Time Frame
Baseline and up to 4 weeks
Title
Percentage of Participants With Change in Hepatic Status
Description
Percentage of participants with a change from baseline in hepatic status and that is sustained for ≥ 24 hours upon repeat measurement, defined as:
Alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
ALT > 5 x ULN
ALT > 10 x ULN
Serum total bilirubin > 1.5 x ULN
Serum total bilirubin > 2 x ULN
Possible Hy's law cases, as defined in the FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation (July 2009).
Time Frame
Baseline and up to 4 weeks
Title
Number of Participants With Treatment-emergent Bleeding Events
Description
Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).
Time Frame
Up to 9 weeks
Title
Percentage of Participants With Treatment-emergent Bleeding Events
Description
Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).
Time Frame
Up to 9 weeks
Title
Percentage of Participants With Binding Antibodies Specific to Apolipoprotein A-I (Apo-A1) and CSL112
Time Frame
Up to 9 weeks
Title
Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 1 for apoA-I and PC
Time Frame
Immediately after end of infusion
Title
Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 4 for apoA-I and PC
Time Frame
Immediately after end of infusion
Title
Plasma apoA-I and Phosphatidylcholine (PC) Accumulation Ratio After Infusion 4
Description
The plasma apoA-I and PC accumulation ratio will be determined for CSL112-treated subjects.
Time Frame
Immediately after end of infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
• Men or women, at least 18 years of age, with evidence of moderate renal impairment (an eGFR ≥ 30 and <60 mL/min/1.73 m2) and myocardial necrosis in a clinical setting consistent with a type I (spontaneous) acute myocardial infarction (AMI).
Exclusion Criteria:
Symptoms, biomarker elevation or electrocardiogram (ECG) changes other than those of the index event that are consistent with a diagnosis of AMI but are likely not due to primary myocardial ischemia
Ongoing hemodynamic instability
Planned coronary artery bypass surgery
Evidence of hepatobiliary disease
History of acute kidney injury (AKI) after previous exposure to an intravenous contrast agent.
History of nephrotic range proteinuria.
Known history of allergy to soy beans or peanuts, immunoglobulin A (IgA) deficiency, antibodies to IgA , or hypersensitivity to CSL112 or any of its components.
Other severe comorbid condition, concurrent medication, or other issue that renders the subject unsuitable for participation in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Danielle Duffy, MD
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
Study Site 16101
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35211
Country
United States
Facility Name
Study Site 16078
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35801
Country
United States
Facility Name
Study Site 16168
City
Concord
State/Province
California
ZIP/Postal Code
94520
Country
United States
Facility Name
Study Site 16130
City
Littleton
State/Province
Colorado
ZIP/Postal Code
80120
Country
United States
Facility Name
Study Site 16135
City
Danbury
State/Province
Connecticut
ZIP/Postal Code
06810
Country
United States
Facility Name
Study Site 16003
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Study Site 16112
City
Boise
State/Province
Idaho
ZIP/Postal Code
83712
Country
United States
Facility Name
Study Site 16208
City
Alexandria
State/Province
Louisiana
ZIP/Postal Code
71301
Country
United States
Facility Name
Study Site 16061
City
Petoskey
State/Province
Michigan
ZIP/Postal Code
49770
Country
United States
Facility Name
Study Site 16056
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Study Site 16014
City
High Point
State/Province
North Carolina
ZIP/Postal Code
27762
Country
United States
Facility Name
Study Site 16018
City
Rapid City
State/Province
South Dakota
ZIP/Postal Code
57701
Country
United States
Facility Name
Study Site 16241
City
Wichita Falls
State/Province
Texas
ZIP/Postal Code
76301
Country
United States
Facility Name
Study Site 17001
City
Freiburg
State/Province
Baden Wuerttemberg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Study Site 17014
City
Frankfurt
State/Province
Hessen
ZIP/Postal Code
65929
Country
Germany
Facility Name
Study Site 17005
City
Berlin
ZIP/Postal Code
10249
Country
Germany
Facility Name
Study Site 17009
City
Berlin
ZIP/Postal Code
10967
Country
Germany
Facility Name
Study Site 17003
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Study Site 17006
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Study Site 18001
City
Budapest
ZIP/Postal Code
1122
Country
Hungary
Facility Name
Study Site 18005
City
Budapest
ZIP/Postal Code
1134
Country
Hungary
Facility Name
Study Site 18007
City
Nyiregyhaza
ZIP/Postal Code
4400
Country
Hungary
Facility Name
Study Site 18003
City
Pecs
ZIP/Postal Code
7624
Country
Hungary
Facility Name
Study Site 18009
City
Szeged
ZIP/Postal Code
6720
Country
Hungary
Facility Name
Study Site 19005
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Study Site 19002
City
Nahariya
ZIP/Postal Code
22100
Country
Israel
Facility Name
Study Site 19008
City
Safed
ZIP/Postal Code
13100
Country
Israel
Facility Name
Study Site 21001
City
Alkmaar
ZIP/Postal Code
1815 JD
Country
Netherlands
Facility Name
Study Site 21006
City
Amsterdam
ZIP/Postal Code
1091 AC
Country
Netherlands
Facility Name
Study Site 21017
City
Amsterfoort
ZIP/Postal Code
3818 TZ
Country
Netherlands
Facility Name
Study Site 21008
City
Nijmegen
ZIP/Postal Code
6525 EC
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
33217027
Citation
Zheng B, Duffy D, Tricoci P, Kastrissios H, Pfister M, Wright SD, Gille A, Tortorici MA. Pharmacometric analyses to characterize the effect of CSL112 on apolipoprotein A-I and cholesterol efflux capacity in acute myocardial infarction patients. Br J Clin Pharmacol. 2021 Jun;87(6):2558-2571. doi: 10.1111/bcp.14666. Epub 2020 Dec 23.
Results Reference
derived
PubMed Identifier
30580130
Citation
Gibson CM, Kerneis M, Yee MK, Daaboul Y, Korjian S, Mehr AP, Tricoci P, Alexander JH, Kastelein JJP, Mehran R, Bode C, Lewis BS, Mehta R, Duffy D, Feaster J, Halabi M, Angiolillo DJ, Duerschmied D, Ophuis TO, Merkely B. The CSL112-2001 trial: Safety and tolerability of multiple doses of CSL112 (apolipoprotein A-I [human]), an intravenous formulation of plasma-derived apolipoprotein A-I, among subjects with moderate renal impairment after acute myocardial infarction. Am Heart J. 2019 Feb;208:81-90. doi: 10.1016/j.ahj.2018.11.008. Epub 2018 Nov 22.
Results Reference
derived
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A Study of CSL112 in Adults With Moderate Renal Impairment and Acute Myocardial Infarction
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