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

Phase 2Not Yet RecruitingNCT07832435

Redx Pharma Ltd180 enrolled

Overview

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.

RXC008 is an investigational GI-restricted inhibitor of ROCK1 and ROCK2 for the treatment of fibrostenosis due to CD. The study will assess efficacy, safety, systemic PK and PD of RXC008 versus placebo in participants with strictures due to CD. This multi-centre, randomized, double-blind, placebo-controlled Phase 2 study will evaluate the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of orally administered RXC008 compared to a matching placebo over a treatment period of up to 48 weeks. Following a formal screening period to confirm eligibility, participants on stable background anti-inflammatory therapy will be randomized 1:1:1 to receive either a high dose of RXC008, a low dose of RXC008, or a matched placebo, administered orally. Key study procedures and protocol-specified assessments will be performed at designated intervals throughout the trial. Radiographic changes in stricture anatomy will be monitored via central reads of Magnetic Resonance Enterography (MRE) scans. while stricture passability will be evaluated via ileocolonoscopy. Additionally, daily patient-reported outcome (S-PRO2) diaries will be utilized to track the severity and frequency of obstructive symptoms directly from the participant's perspective. Regular blood sampling will also be conducted to characterize systemic drug exposure and safety profiles. RXC008 is presented for oral administration. Matched placebo will be presented in identical containers and stored / packaged the same as RXC008. Packaging, labelling and preparation of the study medication will be performed in a way that will ensure blinding throughout the cohort. Primary Objective: To assess the safety and efficacy of RXC008 administered orally daily for up to 24 weeks in participants with strictures due to Crohn's disease who are on stable background anti-inflammatory therapy. Secondary Objective: Characterise the PK and evaluate RXC008 safety and efficacy administered daily for 48 weeks for Crohn's patients on stable background anti-inflammatory therapy. Approximately 180 participants will be randomized 1:1:1 to RXC008 High dose: RXC008 Low dose or placebo.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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).

Outcomes

Primary Outcomes

Absolute change from baseline in primary stricture.

Absolute change from baseline in primary stricture at Week 24, measured by Magnetic Resonance Enterography (MRE).

Time frame: At week 24.

Secondary Outcomes

Change from baseline in stricture passability.

Change from baseline in stricture passability (passable or non-passable) via ileocolonoscope.

Time frame: At week 24 and at week 48.

Radiographic stenosis response.

Radiographic stenosis response (≥25% improvement in primary stricture length or ≥50% improvement in pre-stenotic dilation without worsening of primary stricture length AND no new small bowel stenosis, no new stricture associated fistula, and no new stenotic abscess).

Time frame: At week 24 and at week 48.

Treatment-Emergent Adverse Events.

The incidence of Treatment-Emergent Adverse Events (TEAEs).

Time frame: At week 24 and week 48.

Serious Adverse Events.

The incidence of Serious Adverse Events (SAEs).

Time frame: At week 24 and week 48.

Adverse Events.

The incidence of discontinuations due to Adverse Events (AEs).

Time frame: At week 24 and at week 48.

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

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts