%0 Journal Article
%T The Safety, Tolerability, Pharmacokinetics, and Clinical Efficacy of the NLRX1 agonist NX-13 in Active Ulcerative Colitis: Results of a Phase 1b Study.
%A Verstockt B
%A Vermeire S
%A Peyrin-Biroulet L
%A Mosig R
%A Feagan BG
%A Colombel JF
%A Siegmund B
%A Rieder F
%A Schreiber S
%A Yarur A
%A Panaccione R
%A Dubinsky M
%A Lichtiger S
%A Cataldi F
%A Danese S
%J J Crohns Colitis
%V 18
%N 5
%D 2024 May 31
%M 37952114
%F 10.02
%R 10.1093/ecco-jcc/jjad192
%X <B>OBJECTIVE: </B>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].<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.