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Acute Myocardial InfarctionPhase 2NCT02742103

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

A Phase 2 study testing CSL_112 in people with Acute Myocardial Infarction and Moderate Renal Impairment, run by CSL Behring at 31 sites in 5 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 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CSL_112
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
83 participants
Where
31 sitesin 5 countries
Study dates
Aug 2016to Jun 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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.

Trial locations and contacts

31 sites in 5 countries.

31 sites in 5 countries

United States13 sites

  • Study Site 16208

    Alexandria, Louisiana, 71301

  • Study Site 16101

    Birmingham, Alabama, 35211

  • Study Site 16112

    Boise, Idaho, 83712

  • Study Site 16168

    Concord, California, 94520

  • Study Site 16135

    Danbury, Connecticut, 06810

  • Study Site 16056

    Durham, North Carolina, 27705

  • Study Site 16014

    High Point, North Carolina, 27762

  • Study Site 16078

    Huntsville, Alabama, 35801

  • Study Site 16003

    Jacksonville, Florida, 32209

  • Study Site 16130

    Littleton, Colorado, 80120

  • Study Site 16061

    Petoskey, Michigan, 49770

  • Study Site 16018

    Rapid City, South Dakota, 57701

  • Study Site 16241

    Wichita Falls, Texas, 76301

Other trials in United States

Germany6 sites

  • Study Site 17005

    Berlin, 10249

  • Study Site 17009

    Berlin, 10967

  • Study Site 17003

    Berlin, 13353

  • Study Site 17014

    Frankfurt am Main, Hesse, 65929

  • Study Site 17001

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

  • Study Site 17006

    Hamburg, 20246

Other trials in Germany

Hungary5 sites

  • Study Site 18001

    Budapest, 1122

  • Study Site 18005

    Budapest, 1134

  • Study Site 18007

    Nyíregyháza, 4400

  • Study Site 18003

    Pécs, 7624

  • Study Site 18009

    Szeged, 6720

Other trials in Hungary

Netherlands4 sites

  • Study Site 21001

    Alkmaar, 1815 JD

  • Study Site 21006

    Amsterdam, 1091 AC

  • Study Site 21017

    Amsterfoort, 3818 TZ

  • Study Site 21008

    Nijmegen, 6525 EC

Other trials in Netherlands

Israel3 sites

  • Study Site 19005

    Haifa, 3109601

  • Study Site 19002

    Nahariya, 22100

  • Study Site 19008

    Safed, 13100

Other trials in Israel

About this study

Official title: A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group, Study to Investigate the Safety and Tolerability of Multiple Dose Administration of CSL112 in Subjects With Moderate Renal Impairment and Acute Myocardial Infarction

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).

Being tested
CSL_112, Placebo

What participants receive

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

  • CSL_112Biological

    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 NCT02742103
Study groupRoleWhat they receive
CSL_112ExperimentalCSL112 will be administered intravenously, once weekly for 4 consecutive weeks (4 infusions in total).
Receives: Biological: CSL_112
PlaceboPlacebo comparatorPlacebo will be administered at the same frequency, volume and duration as the CSL112 infusion.
Receives: Other: Placebo

What is being measured

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

  1. 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.

    Measured: Up to 9 weeks

  2. 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.

    Measured: Up to 4 weeks

Secondary outcomes (15)

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

    Measured: Up to 9 weeks

  2. Percentage of Participants With TEAEs

    Measured: Up to 9 weeks

  3. Total Number of TEAEs

    Measured: Up to 9 weeks

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

    Adverse drug reactions or suspected adverse drug reactions are defined as:

    1. All TEAEs, including local tolerability events, that begin during or within 1 hour after the end of an infusion; or
    2. Those TEAEs that the investigator or sponsor indicate may be causally related to product administration; or
    3. All TEAEs for which the Investigator's causality assessment is missing or indeterminate; or
    4. All TEAEs 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 9 weeks

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

    Adverse drug reactions or suspected adverse drug reactions are defined as:

    1. All TEAEs, including local tolerability events, that begin during or within 1 hour after the end of an infusion; or
    2. Those TEAEs that the investigator or sponsor indicate may be causally related to product administration; or
    3. All TEAEs for which the Investigator's causality assessment is missing or indeterminate; or
    4. All TEAEs 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 9 weeks

  6. Number of Participants With Change in Renal Status

    Number of participants with changes in renal status defined as:

    • Absolute increases from baseline in serum creatinine as follows:
    1. ≤ baseline value ii. > 0 to < 0.3 mg/dL iii. ≥ 0.3 to ≤ 0.5 mg/dL iv. > 0.5 mg/dL
    • Increases in serum creatinine that are sustained for ≥ 24 hours upon repeat measurement that are greater than or equal to 1.5 x, 2 x, or 3.0 x the baseline value, or serum creatinine ≥ 4.0 mg/dL
    • Initiation of renal replacement therapy
    • Decrease in eGFR ≥ 25% from baseline starting during the active treatment period and that is sustained at the final study visit

    Measured: Baseline and up to 4 weeks

  7. Percentage of Participants With Change in Renal Status

    Percentage of participants with changes in renal status defined as:

    • Absolute increases from baseline in serum creatinine as follows:
    1. ≤ baseline value ii. > 0 to < 0.3 mg/dL iii. ≥ 0.3 to ≤ 0.5 mg/dL iv. > 0.5 mg/dL
    • Increases in serum creatinine that are sustained for ≥ 24 hours upon repeat measurement that are greater than or equal to 1.5 x, 2 x, or 3.0 x the baseline value, or serum creatinine ≥ 4.0 mg/dL
    • Initiation of renal replacement therapy
    • Decrease in eGFR ≥ 25% from baseline starting during the active treatment period and that is sustained at the final study visit

    Measured: Baseline and up to 4 weeks

  8. Number of Participants With Change in Hepatic Status

    Number of participants with a change from baseline in hepatic status and that is sustained for ≥ 24 hours upon repeat measurement, defined as:

    1. Alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
    2. ALT > 5 x ULN
    3. ALT > 10 x ULN
    4. Serum total bilirubin > 1.5 x ULN
    5. Serum total bilirubin > 2 x ULN
    6. Possible Hy's law cases, as defined in the FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation (July 2009).

    Measured: Baseline and up to 4 weeks

  9. Percentage of Participants With Change in Hepatic Status

    Percentage of participants with a change from baseline in hepatic status and that is sustained for ≥ 24 hours upon repeat measurement, defined as:

    1. Alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN)
    2. ALT > 5 x ULN
    3. ALT > 10 x ULN
    4. Serum total bilirubin > 1.5 x ULN
    5. Serum total bilirubin > 2 x ULN
    6. Possible Hy's law cases, as defined in the FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation (July 2009).

    Measured: Baseline and up to 4 weeks

  10. Number of Participants With Treatment-emergent Bleeding Events

    Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).

    Measured: Up to 9 weeks

  11. Percentage of Participants With Treatment-emergent Bleeding Events

    Bleeding events are as defined by the Bleeding Academic Research Consortium (BARC) criteria (Mehran et al., 2011).

    Measured: Up to 9 weeks

  12. Percentage of Participants With Binding Antibodies Specific to Apolipoprotein A-I (Apo-A1) and CSL112

    Measured: Up to 9 weeks

  13. Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 1 for apoA-I and PC

    Measured: Immediately after end of infusion

  14. Baseline-corrected Plasma Concentration Maximum (Cmax) After Infusion 4 for apoA-I and PC

    Measured: Immediately after end of infusion

  15. Plasma apoA-I and Phosphatidylcholine (PC) Accumulation Ratio After Infusion 4

    The plasma apoA-I and PC accumulation ratio will be determined for CSL112-treated subjects.

    Measured: Immediately after end of infusion

Timeline

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

  1. First posted18 Apr 2016 (estimated)
  2. Study startAug 2016
  3. Primary completionJun 2017
  4. Study completionJun 2017

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 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02742103
Sponsor's protocol ID
CSL112_2001
Other IDs
2015-003017-26, 2015
Status last verified
May 2020
First submitted
30 Mar 2016
Last updated
11 Jun 2020
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

  • 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.

    PubMed 30580130

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CSL_112 in people with Acute Myocardial Infarction and Moderate Renal Impairment, run by CSL Behring at 31 sites in 5 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 1 inclusion and 8 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 11 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, Germany, Hungary, Netherlands, Israel. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percent of Participants With at Least One Occurrence of Treatment-emergent Renal Serious Adverse Events (SAEs) (SAF) (time frame: Up to 9 weeks). The study lists 2 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 NCT02742103, 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 11 Jun 2020.

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