A Study of CSL112 in Healthy Adults and in Adults With Moderate Renal Impairment

NCT02427035 | Completed Phase 1 DMC

• 2 other identifiers: CSL112_10012014-005520-10
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 4

Brief Summary

This is a phase 1 multicenter, randomized, double-blind, placebo-controlled, ascending dose study to investigate the pharmacokinetics (PK), safety, and tolerability of CSL112 in adult subjects with moderate renal impairment and in healthy adult subjects with normal renal function.

Conditions

Acute Myocardial Infarction

Outcome Measures

Primary Outcomes (10)

• Plasma apolipoprotein A-I (apoA-I) and phosphatidylcholine (PC) area under the curve (AUC)

  Baseline corrected plasma apoA-I and PC AUC0-infinity

  Before and at up to 10 time points (during up to 7 days) after infusion

• Plasma apoA-I and PC AUC0-last and AUC 0-t

  AUC from time point zero to the last quantifiable time point before the analyte first returns to baseline (AUC0-last) and/or a partial AUC from baseline to time point t (AUC0-t) with and without baseline correction

  Before and at up to 10 time points (during up to 7 days) after infusion

• Plasma apoA-I and PC Cmax

  Before and at up to 10 time points (during up to 7 days) after infusion

• Plasma apoA-I and PC Tmax

  Before and at up to 10 time points (during up to 7 days) after infusion

• Plasma apoA-I and PC Volume of distribution during terminal phase

  Before and at up to 10 time points (during up to 7 days) after infusion

• Plasma apoA-I and PC clearance

  Before and at up to 10 time points (during up to 7 days) after infusion

• Plasma apoA-I and PC t1/2

  Before and at up to 10 time points (during up to 7 days) after infusion

• Urinary excretion of apoA-I (Ae0-t)

  Amount excreted (Ae) of apoA-I over a collection interval 0-t.

  Before and up to 48 hours after infusion

• Urinary excretion of apoA-I (%fe0-t)

  Percent fraction excreted (%fe) of apoA-I in urine over time interval 0-t, calculated as Ae0-t/Dose x 100.

  Before and up to 48 hours after infusion

• Renal clearance of apoA-I

  Renal clearance of apoA-I, calculated as Ae0-48/AUC0-48

  Before and up to 48 hours after infusion

Secondary Outcomes (16)

• Urinary excretion of sucrose(Ae0-t)

  Before and up to 48 hours after infusion

• Urinary excretion of sucrose (%fe0-t)

  Before and up to 48 hours after infusion

• Urinary excretion of sucrose (clearance)

  Before and up to 48 hours after infusion

• Adverse drug reaction (ADR) or suspected ADR frequency (%)

  Up to approximately 127 days

• Clinically significant changes in routine safety assessments

  Up to approximately 97 days

Study Arms (2)

Low

EXPERIMENTAL

A low dose of either CSL112 or placebo is to be administered as a single intravenous (IV) infusion. The placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.

Biological: CSL112; Other: Placebo

High

EXPERIMENTAL

A high dose of either CSL112 or placebo is to be administered as a single intravenous (IV) infusion. The placebo will be administered at the same frequency, volume and duration as the CSL112 infusion.

Biological: CSL112; Other: Placebo

Interventions

CSL112 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.

High; Low

Placebo OTHER

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

High; Low

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women aged 18 to 85 years (inclusive) of age, with body weight 50 kg or more.
• Subjects with renal impairment (RI) must have stable chronic moderate RI (estimated glomerular filtration rate \[eGFR\] ≥ 30 and \< 60 mL/min/1.73 m2)
• Healthy subjects must have normal renal function (eGFR ≥ 90 mL/min/1.73 m2)

You may not qualify if:

• Evidence of a clinically significant medical condition, disorder or disease
• Evidence of hepatobiliary disease
• Any clinically relevant abnormal laboratory test result
• Known history of allergies, hypersensitivity or deficiencies 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, including: history of cancer, low platelet count, bleeding disorder or coagulopathy, significantly altered electrocardiogram waveform, unstable glycemia control in subjects with diabetes, acute renal failure, recent donation or loss of blood
• Evidence or history of alcohol or substance abuse

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (4)

Study Site - 17101

Berlin, 13353, Germany

Location

Study Site - 17102

Munich, D-81241, Germany

Location

Study Site - 24101

London, SE1 1YR, United Kingdom

Location

Study Site - 24102

Manchester, M13 9WL, United Kingdom

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

• Tortorici MA, Duffy D, Evans R, Feaster J, Gille A, Mant TGK, Wright SD, D'Andrea D. Pharmacokinetics and Safety of CSL112 (Apolipoprotein A-I [Human]) in Adults With Moderate Renal Impairment and Normal Renal Function. Clin Pharmacol Drug Dev. 2019 Jul;8(5):628-636. doi: 10.1002/cpdd.618. Epub 2018 Sep 21.

  PMID: 30240132 DERIVED

MeSH Terms

Interventions

CSL112

Study Officials

• Denise D'Andrea, M.D.

  CSL Behring

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2015
• First Posted: April 27, 2015
• Study Start: May 1, 2015
• Primary Completion: November 1, 2015
• Study Completion: February 1, 2016
• Last Updated: September 19, 2017

Record last verified: 2017-09

Locations

DE (2); GB (2)