The Safety, Tolerability, Pharmacokinetics, and Clinical Efficacy of the NLRX1 agonist NX-13 in Active Ulcerative Colitis: Results of a Phase 1b Study.

Autor:	Verstockt B; Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.; Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium., Vermeire S; Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.; Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium., Peyrin-Biroulet L; Department of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France.; INSERM, NGERE, University of Lorraine, F-54000 Nancy, France.; INFINY Institute, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France.; FHU-CURE, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France.; Groupe Hospitalier privé Ambroise Paré - Hartmann, Paris IBD Center, 92200 Neuilly sur Seine, France.; Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada., Mosig R; Landos Biopharma, Blacksburg, VA, USA., Feagan BG; Department of Medicine, Division of Gastroenterology, University of Western Ontario, London, Ontario, Canada.; Alimentiv Inc, London, Ontario, Canada.; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada., Colombel JF; The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Siegmund B; Division of Gastroenterology, Infectiology and Rheumatology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany., Rieder F; Department of Gastroenterology, Hepatology, and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA., Schreiber S; Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Department of Internal Medicine, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany., Yarur A; Division of Gastroenterology and Hepatology, Center for Inflammatory Bowel Diseases. Cedars Sinai Medical Center, Los Angeles, CA, USA., Panaccione R; Division of Gastroenterology & Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Dubinsky M; Division of Pediatric Gastroenterology and Nutrition, Mount Sinai Kravis Children's Hospital, Icahn School of Medicine Mount Sinai, New York, NY, USA., Lichtiger S; Landos Biopharma, Blacksburg, VA, USA., Cataldi F; Landos Biopharma, Blacksburg, VA, USA., Danese S; Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Journal of Crohn's & colitis [J Crohns Colitis] 2024 May 31; Vol. 18 (5), pp. 762-772.
DOI:	10.1093/ecco-jcc/jjad192
Abstrakt:	Background and Aims: NX-13 activation of NLRX1 reduces intracellular reactive oxygen species and decreases inflammation in animal models of colitis. A phase 1a trial demonstrated a gut-selective pharmacokinetic profile with good tolerability. This phase Ib study aimed to evaluate the safety, tolerability, and pharmacokinetics of NX-13 in patients with active ulcerative colitis [UC]. Methods: We conducted a multicentre, randomized, double-blind, placebo-controlled trial of NX-13 in patients with active UC. Patients with a Mayo Clinic Score of 4-10 were randomly assigned [3:3:3:1 ratio] to three NX-13 oral dose groups (250 mg immediate release [IR], 500 mg IR, or 500 mg delayed release [DR], or placebo) once daily for 4 weeks. Safety and pharmacokinetics were the primary and secondary objectives, respectively. Results: Thirty-eight patients [11 females] were recruited and randomized to placebo [five], NX-13 250 mg IR [11], NX-13 500 mg IR [11], or NX-13 500 mg DR [11] and received at least one dose. There were no serious adverse events or deaths during the trial. One patient [500 mg DR, 1/11] withdrew due to worsening of UC and a second [500 mg IR, 1/11] on the last day of treatment after a panic attack associated with atrial fibrillation. In the efficacy population [36 patients], clinical improvement in rectal bleeding and stool frequency scores relative to placebo were seen as early as week 2 and endoscopic response was seen at week 4. Conclusions: NX-13 was generally safe and well tolerated with early signs of rapid symptom and endoscopic improvement. This novel mechanism of action warrants further investigation. ClinicalTrials.gov: NCT04862741. (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)
Databáze:	MEDLINE
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