Browsing by Author "Maughan, Maureen"

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    ItemOpen Access
    CN-105 in Participants with Acute Supratentorial Intracerebral Hemorrhage (CATCH) Trial.
    (Neurocritical care, 2021-08-23) James, Michael L; Troy, Jesse; Nowacki, Nathaniel; Komisarow, Jordan; Swisher, Christa B; Tucker, Kristi; Hatton, Kevin; Babi, Marc A; Worrall, Bradford B; Andrews, Charles; Woo, Daniel; Kranz, Peter G; Lascola, Christopher; Maughan, Maureen; Laskowitz, Daniel T; CATCH Investigators

    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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    Development of mRNA manufacturing for vaccines and therapeutics: mRNA platform requirements and development of a scalable production process to support early phase clinical trials.
    (Translational research : the journal of laboratory and clinical medicine, 2022-04) Whitley, Jill; Zwolinski, Christopher; Denis, Christian; Maughan, Maureen; Hayles, Leonie; Clarke, David; Snare, Meghan; Liao, Hong; Chiou, Sean; Marmura, Tina; Zoeller, Holly; Hudson, Ben; Peart, John; Johnson, Monica; Karlsson, Amelia; Wang, Yunfei; Nagle, Cynthia; Harris, Cherell; Tonkin, Daniel; Fraser, Stephanie; Capiz, Lieza; Zeno, Christina L; Meli, Yvonne; Martik, Diana; Ozaki, Daniel A; Caparoni, Amy; Dickens, Jason E; Weissman, Drew; Saunders, Kevin O; Haynes, Barton F; Sempowski, Gregory D; Denny, Thomas N; Johnson, Matthew R
    The remarkable success of SARS CoV-2 mRNA-based vaccines and the ensuing interest in mRNA vaccines and therapeutics have highlighted the need for a scalable clinical-enabling manufacturing process to produce such products, and robust analytical methods to demonstrate safety, potency, and purity. To date, production processes have either not been disclosed or are bench-scale in nature and cannot be readily adapted to clinical and commercial scale production. To address these needs, we have advanced an aqueous-based scalable process that is readily adaptable to GMP-compliant manufacturing, and developed the required analytical methods for product characterization, quality control release, and stability testing. We also have demonstrated the products produced at manufacturing scale under such approaches display good potency and protection in relevant animal models with mRNA products encoding both vaccine immunogens and antibodies. Finally, we discuss continued challenges in raw material identification, sourcing and supply, and the cold chain requirements for mRNA therapeutic and vaccine products. While ultimate solutions have yet to be elucidated, we discuss approaches that can be taken that are aligned with regulatory guidance.