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

CSL Behring32 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Acute Myocardial Infarction

Interventions

CSL112BIOLOGICAL

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

PlaceboOTHER

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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) Exclusion Criteria: * 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

Locations (4)

Study Site - 17101

Berlin, Germany

Study Site - 17102

Munich, Germany

Study Site - 24101

London, United Kingdom

Study Site - 24102

Manchester, United Kingdom

Outcomes

Primary Outcomes

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

Baseline corrected plasma apoA-I and PC AUC0-infinity

Time frame: 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

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

Plasma apoA-I and PC Cmax

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

Plasma apoA-I and PC Tmax

Time frame: 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

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

Plasma apoA-I and PC clearance

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

Plasma apoA-I and PC t1/2

Time frame: 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.

Time frame: Before and up to 48 hours after infusion

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

Data from ClinicalTrials.gov

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Secondary Outcomes

Urinary excretion of sucrose(Ae0-t)

Amount of sucrose excreted over a collection interval 0-t.

Time frame: Before and up to 48 hours after infusion

Urinary excretion of sucrose (%fe0-t)

Percent fraction excreted sucrose in urine over time interval 0-t, calculated as Ae0-t/Dose x 100.

Time frame: Before and up to 48 hours after infusion

Urinary excretion of sucrose (clearance)

Renal clearance of sucrose, calculated as Ae0-48/AUC0-48

Time frame: Before and up to 48 hours after infusion

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

The overall percentage of participants with adverse reactions or suspected adverse reactions: 1. That begin during or within 1 hour of an infusion; or 2. That may be causally related to the administration of the investigational product; or 3. For which the Investigator's causality assessment is missing or indeterminate; or 4. 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 approximately 127 days

Clinically significant changes in routine safety assessments

The number of participants with clinically significant changes in any of the following assessments: clinical laboratory tests, physical examinations, body weight, electrocardiograms, vital signs, immunogenicity testing, serology, nucleic acid testing or proteinuria findings.

Time frame: Up to approximately 97 days

Clinically important change in drug-induced liver injury

A clinically important change in drug-induced liver injury is defined as a change (from baseline) in alanine aminotransferase (ALT) greater than 3 times the upper limit of normal (ULN) or a change in total bilirubin greater than 2 times ULN, that is confirmed upon repeat measurement.

Time frame: From baseline (before infusion) up to Day 16.

Clinically important change in renal status

A clinically important change in renal status is defined as a serum creatinine (Cr) increase to ≥ 1.5 x the baseline value that is confirmed upon repeat measurement, or the need for renal replacement therapy.

Time frame: From baseline (before infusion) up to Day 16.

Plasma sucrose AUC

Baseline corrected plasma sucrose AUC0-infinity