Multicentre, Placebo-controlled Randomised, Double Blind, Phase 2 Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of RXC008 in Participants With Strictures Due to Crohn's Disease Following Treatment With Orally Administered RXC008
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 180
- 主要终点
- Absolute change from baseline in primary stricture.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blinded.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
High dose
干预措施: High Dose (Drug)
Placebo
干预措施: Placebo (Drug)
Low dose
干预措施: Low Dose (Drug)
结局指标
主要结局
Absolute change from baseline in primary stricture.
时间窗: At week 24.
Absolute change from baseline in primary stricture at Week 24, measured by Magnetic Resonance Enterography (MRE).
次要结局
- Change from baseline in stricture passability.(At week 24 and at week 48.)
- Radiographic stenosis response.(At week 24 and at week 48.)
- Treatment-Emergent Adverse Events.(At week 24 and week 48.)
- Serious Adverse Events.(At week 24 and week 48.)
- Adverse Events.(At week 24 and at week 48.)