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

Bram Verstockt, Severine Vermeire, Laurent Peyrin-Biroulet, Rebecca Mosig, Brian G. Feagan, Jean Frederic Colombel, Britta Siegmund, Florian Rieder, Stefan Schreiber, Andres Yarur, Remo Panaccione, Marla Dubinsky, Simon Lichtiger, Fabio Cataldi, Silvio Danese

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1 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)762-772
Number of pages11
JournalJournal of Crohn's and Colitis
Volume18
Issue number5
DOIs
StatePublished - 1 May 2024

Keywords

  • immunometabolism
  • NEXUS
  • NLRX1
  • novel mechanism of action
  • NX-13
  • phase 1b
  • Randomized controlled clinical trial

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