A Phase 2, Placebo-Controlled Study of Oral RXC008 for Crohn's Strictures

Crohn's disease (CD) is chronic inflammatory bowel disease where any part of the Gastrointestinal (GI) tract can become inflamed and develop fibrotic strictures. Intestinal strictures cause abdominal distension, cramping, dietary restrictions, nausea, vomiting, abdominal pain, and postprandial abdominal pain, which significantly impact patient quality of life. Rho-associated coiled-coil kinase (ROCK) family of proteins including ROCK1 and ROCK2 have been shown to play an important role in these fibrotic strictures. The investigational agent, RXC008, is an inhibitor of the activity of ROCK1 and ROCK2. The study will assess efficacy, safety, PK and PD of RXC008 in comparison with placebo for up to 48 weeks in participants with fibrotic strictures who are also receiving standard-of care background anti-inflammatory therapy.

Inclusion Criteria: * BMI \>16 to ≤40 kg/m2; written informed consent. * Symptomatic strictures based on S-PRO2 criteria. * ≤2 small bowel strictures (naïve, native or anastomotic) confirmed by central MRE read; primary lesion is most distal and reachable by ileocolonoscopy. * MRE features consistent with stricture, including: * Luminal narrowing (≥50%). * Bowel wall thickening (≥25%). * Pre-stenotic dilatation (≥25 mm). * Stable background Crohn's therapy after induction with no planned changes for study duration (biologics must be stable for ≥12 weeks prior to screening, with shorter windows for other medication classes as defined in the protocol). * Screening labs and vital signs within protocol-defined limits; pregnancy prevention requirements met. Exclusion Criteria: * Severe disease activity as measured by Crohn's Disease Activity Index (CDAI). * Other colitis diagnoses (e.g. ulcerative, indeterminate, ischaemic, NSAID-induced, microscopic, radiation). * Intestinal dysplasia/malignancy. * Likely to require endoscopic balloon dilation or surgery within 6 months, in the opinion of the investigator. * Received either endoscopic balloon dilation or intestinal surgery within the past 6 months. * Major surgery within 8 weeks pre-randomisation or planned during the study; extensive resections/proctocolectomy; short gut syndrome (≤200 cm small bowel). * Active septic/penetrating complications of CD (e.g., fistulas, abscess, phlegmon), pouches/ostomies, anal/perianal strictures, toxic megacolon, inability to eat, or current hospitalisation for Crohn's disease. * Prohibited concomitant medications; prior RXC008 exposure; recent/concurrent participation in another interventional study (per protocol windows).