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CN-105 in Participants with Acute Supratentorial Intracerebral Hemorrhage (CATCH) Trial

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A Correction to this article was published on 24 June 2022

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Abstract

Background

Endogenous apolipoprotein (apo) E mediates neuroinflammatory responses and recovery after brain injury. Exogenously administered apoE-mimetic peptides effectively penetrate the central nervous system compartment and downregulate acute inflammation. CN-105 is a novel apoE-mimetic pentapeptide with excellent evidence of functional and histological improvement in preclinical models of intracerebral hemorrhage (ICH). The CN-105 in participants with Acute supraTentorial intraCerebral Hemorrhage (CATCH) trial is a first-in-disease-state multicenter open-label trial evaluating safety and feasability of CN-105 administration in patients with acute primary supratentorial ICH.

Methods

Eligible patients were aged 30–80 years, had confirmed primary supratentorial ICH, and were able to intiate CN-105 administration (1.0 mg/kg every 6 h for 72 h) within 12 h of symptom onset. A priori defined safety end points, including hematoma volume, pharmacokinetics, and 30-day neurological outcomes, were analyzed. For clinical outcomes, CATCH participants were compared 1:1 with a closely matched contemporary ICH cohort through random selection. Hematoma volumes determined from computed tomography images on days 0, 1, 2, and 5 and ordinal modified Rankin Scale score at 30 days after ICH were compared.

Results

In 38 participants enrolled across six study sites in the United States, adverse events occurred at an expected rate without increase in hematoma expansion or neurological deterioration. CN-105 treatment had an odds ratio (95% confidence interval) of 2.69 (1.31–5.51) for lower 30-day modified Rankin Scale score, after adjustment for ICH score, sex, and race/ethnicity, as compared with a matched contemporary cohort.

Conclusions

CN-105 administration represents an excellent translational candidate for treatment of acute ICH because of its safety, dosing feasibility, favorable pharmacokinetics, and possible improvement in neurological recovery.

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Acknowledgements

The authors would like to express their sincere gratitude to the full list of CATCH Investigators (Supplemental Table 1) for their tireless efforts in executing this trial.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Duke University, Durham, NC, USA

    Michael L. James & Daniel T. Laskowitz

  2. Department of Neurology, Duke University, Durham, NC, USA

    Michael L. James, Christa B. Swisher & Daniel T. Laskowitz

  3. Duke Clinical Research Institute, Duke University, Durham, NC, USA

    Michael L. James & Daniel T. Laskowitz

  4. Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA

    Jesse Troy

  5. Hospital Care, Hattiesburg Clinic Neurology, Hattiesburg, MS, USA

    Nathaniel Nowacki

  6. Department of Neurosurgery, Duke University, Durham, NC, USA

    Jordan Komisarow

  7. Department of Neurology, Wake Forest-Baptist Health, Winston-Salem, NC, USA

    Kristi Tucker

  8. Department of Anesthesiology, University of Kentucky, Lexington, KY, USA

    Kevin Hatton

  9. Departments of Neurology and Neurosurgery, University of Florida, Gainesville, FL, USA

    Marc A. Babi

  10. Departments of Neurology and Public Health Sciences, University of Virginia, Charlottesvile, VA, USA

    Bradford B. Worrall

  11. Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, USA

    Charles Andrews

  12. Department of Neurology, University of Cincinnati, Cincinnati, OH, USA

    Daniel Woo

  13. Department of Radiology, Duke University, Durham, NC, USA

    Peter G. Kranz & Christopher Lascola

  14. AegisCN, LLC, Durham, NC, USA

    Maureen Maughan & Daniel T. Laskowitz

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  1. Michael L. James
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Consortia

the CATCH Investigators

Contributions

MLJ designed the research, analyzed and interpreted the data, wrote the manuscript, and prepared the figures. JT designed portions of the research, analyzed and interpreted the data, wrote portions of the manuscript, and prepared the figures. NN analyzed and interpreted data, wrote portions of the manuscript, and offered critical edits to the manuscript. JK, CBS, KT, KH, MAB, BBW, and CA performed the research and collected data, and offered critical edits to the manuscript. DW designed part of the research, performed the research and collected data, and offered critical edits to the manuscript. PGK and Lascola analyzed and interpreted data, wrote portions of the manuscript, and offered critical edits to the manuscript. MM wrote portions of the manuscript and offered critical edits to the manuscript. DTL designed portions of the research, analyzed and interpreted the data, wrote portions of the manuscript, and prepared the figures. Authorship requirements have been met, and the final manuscript was approved by all authors.

Corresponding author

Correspondence to Michael L. James.

Ethics declarations

Source of Support

The United States Food and Drug Administration provided grant funding for this trial (FDA FD-R-5387; DTL, MM). Aegis-CN provided the study drug, CN-105, and funding for this trial.

Conflict of interest

DTL is an officer and has equity in Aegis-CN. Duke University has equity and an intellectual property stake in CN-105 and might benefit if proven effective and successful commercially. MLJ serves as Principal Investigator for the CATCH trial, receiving grant funding for the trial from Aegis-CN. JT received consulting fees from Aegis-CN during the conduct of this trial. MM is an officer in Aegis-CN. All other authors have no conflicts to report.

Ethical Approval/Informed Consent

CATCH was approved by central institutional review board, Copernicus Group Independent Review Board, and by each participating site’s institutional review board. The study was performed in accordance with ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consent was obtained from all individual participants or their legal authorized representatives prior to engagement in study procedures. Because of potential conflicts of interest with Duke University, which holds a portion of intellectual property, CATCH was required to have all primary data provenance and statistical analyses performed by a third party not financially related to Duke University (Pharpoint). Further, oversight of the study was performed using Data Safety and Monitoring Board Plus format, for which all participants were external to Duke and whose express duties included examining any potential conflicts of interest.

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the CATCH Investigators: Full list in Supplemental Table 1.

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James, M.L., Troy, J., Nowacki, N. et al. CN-105 in Participants with Acute Supratentorial Intracerebral Hemorrhage (CATCH) Trial. Neurocrit Care 36, 216–225 (2022). https://doi.org/10.1007/s12028-021-01287-0

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