A Study of CSL112 in Adults With Moderate Renal Impairment and Acute Myocardial Infarction

Acute Myocardial Infarction Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02742103
• Other study ID #: CSL112_2001
• Secondary ID: 2015-003017-26
• Status: Completed
• Phase: Phase 2
• Start date: August 2016
• Est. completion date: June 2017

Study information

• Verified date: May 2020
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Moderate Renal Impairment
• Myocardial Infarction
• Renal Insufficiency

Intervention

Biological:
• 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.

Other:
• Placebo
0.9% weight/volume sodium chloride solution (ie, normal saline)

Locations

Country	Name	City	State
Germany	Study Site 17003	Berlin
Germany	Study Site 17005	Berlin
Germany	Study Site 17009	Berlin
Germany	Study Site 17014	Frankfurt	Hessen
Germany	Study Site 17001	Freiburg	Baden Wuerttemberg
Germany	Study Site 17006	Hamburg
Hungary	Study Site 18001	Budapest
Hungary	Study Site 18005	Budapest
Hungary	Study Site 18007	Nyiregyhaza
Hungary	Study Site 18003	Pecs
Hungary	Study Site 18009	Szeged
Israel	Study Site 19005	Haifa
Israel	Study Site 19002	Nahariya
Israel	Study Site 19008	Safed
Netherlands	Study Site 21001	Alkmaar
Netherlands	Study Site 21006	Amsterdam
Netherlands	Study Site 21017	Amsterfoort
Netherlands	Study Site 21008	Nijmegen
United States	Study Site 16208	Alexandria	Louisiana
United States	Study Site 16101	Birmingham	Alabama
United States	Study Site 16112	Boise	Idaho
United States	Study Site 16168	Concord	California
United States	Study Site 16135	Danbury	Connecticut
United States	Study Site 16056	Durham	North Carolina
United States	Study Site 16014	High Point	North Carolina
United States	Study Site 16078	Huntsville	Alabama
United States	Study Site 16003	Jacksonville	Florida
United States	Study Site 16130	Littleton	Colorado
United States	Study Site 16061	Petoskey	Michigan
United States	Study Site 16018	Rapid City	South Dakota
United States	Study Site 16241	Wichita Falls	Texas

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Germany,  Hungary,  Israel,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 9 weeks
Primary	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.	Up to 4 weeks
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs)		Up to 9 weeks
Secondary	Percentage of Participants With TEAEs		Up to 9 weeks
Secondary	Total Number of TEAEs		Up to 9 weeks
Secondary	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.	Up to 9 weeks
Secondary	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.	Up to 9 weeks
Secondary	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	Baseline and up to 4 weeks
Secondary	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	Baseline and up to 4 weeks
Secondary	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).	Baseline and up to 4 weeks
Secondary	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).	Baseline and up to 4 weeks
Secondary	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).	Up to 9 weeks
Secondary	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).	Up to 9 weeks
Secondary	Percentage of Participants With Binding Antibodies Specific to Apolipoprotein A-I (Apo-A1) and CSL112		Up to 9 weeks
Secondary	Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 1 for apoA-I and PC		Immediately after end of infusion
Secondary	Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 4 for apoA-I and PC		Immediately after end of infusion
Secondary	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.	Immediately after end of infusion