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Trial record 2 of 7 for:    CSL-112

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

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ClinicalTrials.gov Identifier: NCT02427035
Recruitment Status : Completed
First Posted : April 27, 2015
Last Update Posted : September 19, 2017
Sponsor:
Information provided by (Responsible Party):
CSL Behring

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.

Condition or disease Intervention/treatment Phase
Acute Myocardial Infarction Biological: CSL112 Other: Placebo Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo-controlled, Pharmacokinetic, Safety and Tolerability Study of CSL112 in Adult Subjects With Moderate Renal Impairment and in Healthy Adult Subjects With Normal Renal Function
Study Start Date : May 2015
Actual Primary Completion Date : November 2015
Actual Study Completion Date : February 2016

Arm Intervention/treatment
Experimental: Low
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
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)

Experimental: High
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
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)




Primary Outcome Measures :
  1. Plasma apolipoprotein A-I (apoA-I) and phosphatidylcholine (PC) area under the curve (AUC) [ Time Frame: Before and at up to 10 time points (during up to 7 days) after infusion ]
    Baseline corrected plasma apoA-I and PC AUC0-infinity

  2. Plasma apoA-I and PC AUC0-last and AUC 0-t [ Time Frame: Before and at up to 10 time points (during up to 7 days) after infusion ]
    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

  3. Plasma apoA-I and PC Cmax [ Time Frame: Before and at up to 10 time points (during up to 7 days) after infusion ]
  4. Plasma apoA-I and PC Tmax [ Time Frame: Before and at up to 10 time points (during up to 7 days) after infusion ]
  5. 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 ]
  6. Plasma apoA-I and PC clearance [ Time Frame: Before and at up to 10 time points (during up to 7 days) after infusion ]
  7. Plasma apoA-I and PC t1/2 [ Time Frame: Before and at up to 10 time points (during up to 7 days) after infusion ]
  8. Urinary excretion of apoA-I (Ae0-t) [ Time Frame: Before and up to 48 hours after infusion ]
    Amount excreted (Ae) of apoA-I over a collection interval 0-t.

  9. Urinary excretion of apoA-I (%fe0-t) [ Time Frame: Before and up to 48 hours after infusion ]
    Percent fraction excreted (%fe) of apoA-I in urine over time interval 0-t, calculated as Ae0-t/Dose x 100.

  10. Renal clearance of apoA-I [ Time Frame: Before and up to 48 hours after infusion ]
    Renal clearance of apoA-I, calculated as Ae0-48/AUC0-48


Secondary Outcome Measures :
  1. Urinary excretion of sucrose(Ae0-t) [ Time Frame: Before and up to 48 hours after infusion ]
    Amount of sucrose excreted over a collection interval 0-t.

  2. Urinary excretion of sucrose (%fe0-t) [ Time Frame: Before and up to 48 hours after infusion ]
    Percent fraction excreted sucrose in urine over time interval 0-t, calculated as Ae0-t/Dose x 100.

  3. Urinary excretion of sucrose (clearance) [ Time Frame: Before and up to 48 hours after infusion ]
    Renal clearance of sucrose, calculated as Ae0-48/AUC0-48

  4. Adverse drug reaction (ADR) or suspected ADR frequency (%) [ Time Frame: Up to approximately 127 days ]

    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.

  5. Clinically significant changes in routine safety assessments [ Time Frame: Up to approximately 97 days ]
    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.

  6. Clinically important change in drug-induced liver injury [ Time Frame: From baseline (before infusion) up to Day 16. ]
    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.

  7. Clinically important change in renal status [ Time Frame: From baseline (before infusion) up to Day 16. ]
    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.

  8. Plasma sucrose AUC [ Time Frame: Before and at up to 7 time points (during up to 2 days) after infusion ]
    Baseline corrected plasma sucrose AUC0-infinity

  9. Plasma sucrose AUC0-last and AUC 0-t [ Time Frame: Before and at up to 7 time points (during up to 2 days) after infusion ]
    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 y (AUC0-t) with and without baseline correction

  10. Plasma sucrose Cmax [ Time Frame: Before and at up to 7 time points (during up to 2 days) after infusion ]
  11. Plasma sucrose Tmax [ Time Frame: Before and at up to 7 time points (during up to 2 days) after infusion ]
  12. Plasma sucrose Volume of distribution during terminal phase [ Time Frame: Before and at up to 7 time points (during up to 2 days) after infusion ]
  13. Plasma sucrose Clearance [ Time Frame: Before and at up to 7 time points (during up to 2 days) after infusion ]
  14. Plasma sucrose t1/2 [ Time Frame: Before and at up to 7 time points (during up to 2 days) after infusion ]
  15. Adverse drug reaction (ADR) or suspected ADR frequency [ Time Frame: Up to approximately 127 days ]

    The overall number 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.

  16. Number of subjects with AEs [ Time Frame: After the start of infusion up to approximately 127 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02427035


Locations
Germany
Study Site - 17101
Berlin, Germany, 13353
Study Site - 17102
Munich, Germany, D-81241
United Kingdom
Study Site - 24101
London, United Kingdom, SE1 1YR
Study Site - 24102
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Denise D'Andrea, M.D. CSL Behring

Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT02427035     History of Changes
Other Study ID Numbers: CSL112_1001
2014-005520-10 ( EudraCT Number )
First Posted: April 27, 2015    Key Record Dates
Last Update Posted: September 19, 2017
Last Verified: September 2017

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Renal Insufficiency
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Kidney Diseases
Urologic Diseases