A Phase 1, Multicentre, 2-Part, Randomised, Parallel-arm, Placebo-controlled, Partially Double-blind Study to Evaluate the Safety and Target Engagement of EXL01 in the Maintenance of Steroid-induced Clinical Response or Remission in Participants With Mild to Moderate Crohn's Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 8
- 试验地点
- 5
- 主要终点
- The systemic and intestinal safety and tolerability of orally administered EXL01
研究概览
简要总结
A Phase 1, 2-part, multicentre study to evaluate the safety and preliminary efficacy of the oral administration of EXL01 in the maintenance of corticosteroid-induced clinical response/remission in participants with mild to moderate Crohn's Disease (CD).
详细描述
Initially, all participants will received standard of care (SoC) corticosteroid induction therapy for 3 to 7 weeks. Participants who meet the protocol defined criteria for response after corticosteroid therapy will enter a Maintenance Period. Participants not in clinical response/remission at the end of the Induction Period will discontinue the study without further study treatment. In the Maintenance Period, participants will receive oral EXL01 or placebo in combination with corticosteroid treatment (that is progressively tapered) and be monitored for safety and efficacy.
The study will be conducted in 2 parts:
- Part A: Participants eligible for maintenance treatment will receive open-label oral EXL01 for up to 24 weeks.
- Part B: Participants eligible for maintenance treatment will be randomised 2:1 to receive double blind oral EXL01 or placebo for up to 24 weeks.
Participants will be monitored for 30 days after end-of-treatment.
Due to the low recruitment rate into Part A, the study was discontinued early; Part B did not start.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Part A: None (Open-label). Part B: Double-blind.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must meet all of the following criteria at the start of the Induction Period:
- •Male or female aged ≥18 years and <75 years at the time of providing informed consent.
- •A diagnosis of CD with ileal involvement for at least 3 months prior to Screening.
- •A CDAI score >180 and <
- •Part B only: Active mucosal inflammation.
排除标准
- •Stricture with obstructive syndrome <3 months prior to Screening.
- •Stenosis making endoscopic access to the terminal ileum difficult.
- •Received treatment with high dose corticosteroid (≥40 mg prednisone daily) for >5 weeks within 3 months prior to Screening.
- •Part B only: Received >3 prior biologic treatments or JAK inhibitors for CD including infliximab, ustekinumab, vedolizumab, adalimumab, certolizumab, risankizumab, and upadacitinib.
- •Major surgery or significant trauma ≤4 weeks prior to Screening.
- •Small bowel resection >1 m in total or clinical manifestations of short bowel syndrome.
- •Current stoma (ileostomy or a colostomy) or had a stoma in the last 6 months or any other intraabdominal surgery within 3 months prior to Screening.
- •Started or stopped immunosuppressive therapy (thiopurine, methotrexate, tacrolimus, or other classical immunosuppressant) within 3 months prior to Screening.
- •Received faecal microbial transplant within 3 months prior to Screening.
- •Systemic infection or other serious infection requiring systemic treatment within 30 days prior to Screening.
- •Pregnant, breastfeeding, or expecting to conceive during the study.
研究组 & 干预措施
Part A (Open-Label EXL01 Maintenance Therapy)
Oral EXL01 once daily for up to 24 weeks (after SoC corticosteroid induction therapy).
干预措施: EXL01 (Drug)
Part A (Open-Label EXL01 Maintenance Therapy)
Oral EXL01 once daily for up to 24 weeks (after SoC corticosteroid induction therapy).
干预措施: SoC corticosteroid - Induction Period (Other)
Part A (Open-Label EXL01 Maintenance Therapy)
Oral EXL01 once daily for up to 24 weeks (after SoC corticosteroid induction therapy).
干预措施: SoC corticosteroid - Tapering (Other)
Part B (EXL01 Maintenance Therapy)
Oral EXL01 once daily for up to 24 weeks (after SoC corticosteroid induction therapy).
干预措施: EXL01 (Drug)
Part B (EXL01 Maintenance Therapy)
Oral EXL01 once daily for up to 24 weeks (after SoC corticosteroid induction therapy).
干预措施: SoC corticosteroid - Induction Period (Other)
Part B (EXL01 Maintenance Therapy)
Oral EXL01 once daily for up to 24 weeks (after SoC corticosteroid induction therapy).
干预措施: SoC corticosteroid - Tapering (Other)
Part B (Placebo Maintenance Therapy)
Oral EXL01 matched placebo once daily for up to 24 weeks (after SoC corticosteroid induction therapy).
干预措施: Placebo (Drug)
Part B (Placebo Maintenance Therapy)
Oral EXL01 matched placebo once daily for up to 24 weeks (after SoC corticosteroid induction therapy).
干预措施: SoC corticosteroid - Induction Period (Other)
Part B (Placebo Maintenance Therapy)
Oral EXL01 matched placebo once daily for up to 24 weeks (after SoC corticosteroid induction therapy).
干预措施: SoC corticosteroid - Tapering (Other)
结局指标
主要结局
The systemic and intestinal safety and tolerability of orally administered EXL01
时间窗: Up to 43 weeks
Number of participants with adverse events (AE\[s\]). Number of participants with treatment discontinuations due to an AE. AEs assessed by CTCAE v5.0
次要结局
- Time to clinical relapse in participants with CD treated with EXL01 to participants treated with placebo (Part B only)(Maintenance Period Baseline to Week 24)
- Comparison of the SES-CD and histology of the intestinal mucosa in participants with CD treated with EXL01 to participants treated with placebo (Part B only)(Maintenance Period Baseline to Week 24)
- Proportion of participants with an endoscopic response at Week 24(Maintenance Period Week 24)
- Proportion of participants in steroid free clinical remission and mucosal healing and normal inflammatory markers at Week 24(Maintenance Period Week 24)
- Proportion of participants in steroid-free clinical remission at Week 24(Maintenance Period Week 24)
- Proportion of participants in steroid-free clinical remission and mucosal healing at Week 24(Maintenance Period Week 24)
- Comparison of the evolution of the faecal and mucosa-associated microbiota in participants with CD treated with EXL01 to participants treated with placebo (Part B only)(Maintenance Period Baseline to Week 24)