Clinical trial NCT02742103: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myocardial Infarction
Moderate Renal Impairment
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2016-04-18
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).


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.

Primary outcomes:
measure: Percent of Participants With at Least One Occurrence of Treatment-emergent Renal Serious Adverse Events (SAEs) (SAF)
timeFrame: Up to 9 weeks
measure: Percent of Participants With Treatment-emergent Acute Kidney Injury (AKI )
timeFrame: Up to 4 weeks
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 9 weeks
measure: Percentage of Participants With TEAEs
timeFrame: Up to 9 weeks
measure: Total Number of TEAEs
timeFrame: Up to 9 weeks
measure: Number of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR
timeFrame: Up to 9 weeks
measure: Percentage of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR
timeFrame: Up to 9 weeks
measure: Number of Participants With Change in Renal Status
timeFrame: Baseline and up to 4 weeks
measure: Percentage of Participants With Change in Renal Status
timeFrame: Baseline and up to 4 weeks
measure: Number of Participants With Change in Hepatic Status
timeFrame: Baseline and up to 4 weeks
measure: Percentage of Participants With Change in Hepatic Status
timeFrame: Baseline and up to 4 weeks
measure: Number of Participants With Treatment-emergent Bleeding Events
timeFrame: Up to 9 weeks
measure: Percentage of Participants With Treatment-emergent Bleeding Events
timeFrame: Up to 9 weeks
measure: Percentage of Participants With Binding Antibodies Specific to Apolipoprotein A-I (Apo-A1) and CSL112
timeFrame: Up to 9 weeks
measure: Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 1 for apoA-I and PC
timeFrame: Immediately after end of infusion
measure: Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 4 for apoA-I and PC
timeFrame: Immediately after end of infusion
measure: Plasma apoA-I and Phosphatidylcholine (PC) Accumulation Ratio After Infusion 4
timeFrame: Immediately after end of infusion
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Study Site 16101
state: Alabama
city: Huntsville
country: United States
facility: Study Site 16078
state: Alabama
city: Concord
country: United States
facility: Study Site 16168
state: California
city: Littleton
country: United States
facility: Study Site 16130
state: Colorado
city: Danbury
country: United States
facility: Study Site 16135
state: Connecticut
city: Jacksonville
country: United States
facility: Study Site 16003
state: Florida
city: Boise
country: United States
facility: Study Site 16112
state: Idaho
city: Alexandria
country: United States
facility: Study Site 16208
state: Louisiana
city: Petoskey
country: United States
facility: Study Site 16061
state: Michigan
city: Durham
country: United States
facility: Study Site 16056
state: North Carolina
city: High Point
country: United States
facility: Study Site 16014
state: North Carolina
city: Rapid City
country: United States
facility: Study Site 16018
state: South Dakota
city: Wichita Falls
country: United States
facility: Study Site 16241
state: Texas
city: Freiburg
country: Germany
facility: Study Site 17001
state: Baden Wuerttemberg
city: Frankfurt
country: Germany
facility: Study Site 17014
state: Hessen
city: Berlin
country: Germany
facility: Study Site 17005
city: Berlin
country: Germany
facility: Study Site 17009
city: Berlin
country: Germany
facility: Study Site 17003
city: Hamburg
country: Germany
facility: Study Site 17006
city: Budapest
country: Hungary
facility: Study Site 18001
city: Budapest
country: Hungary
facility: Study Site 18005
city: Nyiregyhaza
country: Hungary
facility: Study Site 18007
city: Pecs
country: Hungary
facility: Study Site 18003
city: Szeged
country: Hungary
facility: Study Site 18009
city: Haifa
country: Israel
facility: Study Site 19005
city: Nahariya
country: Israel
facility: Study Site 19002
city: Safed
country: Israel
facility: Study Site 19008
city: Alkmaar
country: Netherlands
facility: Study Site 21001
city: Amsterdam
country: Netherlands
facility: Study Site 21006
city: Amsterfoort
country: Netherlands
facility: Study Site 21017
city: Nijmegen
country: Netherlands
facility: Study Site 21008
Study officials:
affiliation: CSL Behring
name: Danielle Duffy, MD
role: STUDY_DIRECTOR
References:
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.
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.