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Acute Myocardial InfarctionPhase 1NCT02427035

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

A Phase 1 study testing CSL112 in people with Acute Myocardial Infarction, run by CSL Behring at 4 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Acute Myocardial Infarction
What is being tested?
CSL112
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
32 participants
Where
4 sitesin 2 countries
Study dates
May 2015to Feb 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

Germany2 sites

  • Study Site - 17101

    Berlin, 13353

  • Study Site - 17102

    Munich, D-81241

Other trials in Germany

United Kingdom2 sites

  • Study Site - 24101

    London, SE1 1YR

  • Study Site - 24102

    Manchester, M13 9WL

Other trials in United Kingdom

About this study

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

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.

Being tested
CSL112, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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)

Study groups in NCT02427035
Study groupRoleWhat they receive
LowExperimentalA 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.
Receives: Biological: CSL112; Other: Placebo
HighExperimentalA 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.
Receives: Biological: CSL112; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Baseline corrected plasma apoA-I and PC AUC0-infinity

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

  2. 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

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

  3. Plasma apoA-I and PC Cmax

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

  4. Plasma apoA-I and PC Tmax

    Measured: 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

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

  6. Plasma apoA-I and PC clearance

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

  7. Plasma apoA-I and PC t1/2

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

  8. Urinary excretion of apoA-I (Ae0-t)

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

    Measured: Before and up to 48 hours after infusion

  9. 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.

    Measured: Before and up to 48 hours after infusion

  10. Renal clearance of apoA-I

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

    Measured: Before and up to 48 hours after infusion

Secondary outcomes (16)

  1. Urinary excretion of sucrose(Ae0-t)

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

    Measured: Before and up to 48 hours after infusion

  2. Urinary excretion of sucrose (%fe0-t)

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

    Measured: Before and up to 48 hours after infusion

  3. Urinary excretion of sucrose (clearance)

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

    Measured: Before and up to 48 hours after infusion

  4. 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.

    Measured: Up to approximately 127 days

  5. 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.

    Measured: Up to approximately 97 days

  6. 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.

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

  7. 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.

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

  8. Plasma sucrose AUC

    Baseline corrected plasma sucrose AUC0-infinity

    Measured: Before and at up to 7 time points (during up to 2 days) after infusion

  9. Plasma sucrose 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 y (AUC0-t) with and without baseline correction

    Measured: Before and at up to 7 time points (during up to 2 days) after infusion

  10. Plasma sucrose Cmax

    Measured: Before and at up to 7 time points (during up to 2 days) after infusion

  11. Plasma sucrose Tmax

    Measured: Before and at up to 7 time points (during up to 2 days) after infusion

  12. Plasma sucrose Volume of distribution during terminal phase

    Measured: Before and at up to 7 time points (during up to 2 days) after infusion

  13. Plasma sucrose Clearance

    Measured: Before and at up to 7 time points (during up to 2 days) after infusion

  14. Plasma sucrose t1/2

    Measured: Before and at up to 7 time points (during up to 2 days) after infusion

  15. Adverse drug reaction (ADR) or suspected ADR frequency

    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.

    Measured: Up to approximately 127 days

  16. Number of subjects with AEs

    Measured: After the start of infusion up to approximately 127 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Apr 2015 (estimated)
  2. Study startMay 2015
  3. Primary completionNov 2015
  4. Study completionFeb 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02427035
Sponsor's protocol ID
CSL112_1001
Other IDs
2014-005520-10, 2014
Status last verified
Sep 2017
First submitted
20 Apr 2015
Last updated
19 Sep 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 33217027

  • 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.

    PubMed 30240132

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CSL112 in people with Acute Myocardial Infarction, run by CSL Behring at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02427035, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2017.

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