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

NCT02742103 | Completed Phase 2 Results DMC

• 2 other identifiers: CSL112_20012015-003017-26
• Study Type: interventional
• Target: 83
• Locations: 5 countries
• Sites: 31

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).

Conditions

Acute Myocardial Infarction; Moderate Renal Impairment

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (15)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  Up to 9 weeks

• Percentage of Participants With TEAEs

  Up to 9 weeks

• Total Number of TEAEs

  Up to 9 weeks

• Number of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR

  Up to 9 weeks

• Percentage of Participants With Treatment-emergent Adverse Drug Reaction (ADR) or Suspected ADR

  Up to 9 weeks

Study Arms (2)

CSL_112

EXPERIMENTAL

CSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).

Biological: CSL_112

Placebo

PLACEBO COMPARATOR

Placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.

Other: Placebo

Interventions

CSL_112 BIOLOGICAL

CSL112 is a novel formulation of apolipoprotein A-I (apoA-I) purified from human plasma and reconstituted to form high-density lipoprotein (HDL) particles.

CSL_112

Placebo OTHER

0.9% weight/volume sodium chloride solution (ie, normal saline)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (31)

Study Site 16101

Birmingham, Alabama, 35211, United States

Location

Study Site 16078

Huntsville, Alabama, 35801, United States

Location

Study Site 16168

Concord, California, 94520, United States

Location

Study Site 16130

Littleton, Colorado, 80120, United States

Location

Study Site 16135

Danbury, Connecticut, 06810, United States

Location

Study Site 16003

Jacksonville, Florida, 32209, United States

Location

Study Site 16112

Boise, Idaho, 83712, United States

Location

Study Site 16208

Alexandria, Louisiana, 71301, United States

Location

Study Site 16061

Petoskey, Michigan, 49770, United States

Location

Study Site 16056

Durham, North Carolina, 27705, United States

Location

Study Site 16014

High Point, North Carolina, 27762, United States

Location

Study Site 16018

Rapid City, South Dakota, 57701, United States

Location

Study Site 16241

Wichita Falls, Texas, 76301, United States

Location

Study Site 17001

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Study Site 17014

Frankfurt am Main, Hesse, 65929, Germany

Location

Study Site 17005

Berlin, 10249, Germany

Location

Study Site 17009

Berlin, 10967, Germany

Location

Study Site 17003

Berlin, 13353, Germany

Location

Study Site 17006

Hamburg, 20246, Germany

Location

Study Site 18001

Budapest, 1122, Hungary

Location

Study Site 18005

Budapest, 1134, Hungary

Location

Study Site 18007

Nyíregyháza, 4400, Hungary

Location

Study Site 18003

Pécs, 7624, Hungary

Location

Study Site 18009

Szeged, 6720, Hungary

Location

Study Site 19005

Haifa, 3109601, Israel

Location

Study Site 19002

Nahariya, 22100, Israel

Location

Study Site 19008

Safed, 13100, Israel

Location

Study Site 21001

Alkmaar, 1815 JD, Netherlands

Location

Study Site 21006

Amsterdam, 1091 AC, Netherlands

Location

Study Site 21017

Amsterfoort, 3818 TZ, Netherlands

Location

Study Site 21008

Nijmegen, 6525 EC, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 33217027 DERIVED

• 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.

  PMID: 30580130 DERIVED

Results Point of Contact

• Title: Trial Registration Coordinator
• Organization: CSL Behring

clinicaltrials@cslbehring.com

6108784000

Study Officials

• Danielle Duffy, MD

  CSL Behring

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2016
• First Posted: April 18, 2016
• Study Start: August 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: June 11, 2020
• Results First Posted: June 11, 2020

Record last verified: 2020-05

Locations

US (13); NL (4); HU (5); DE (6); IL (3)