An Open, Sequential Dose-Escalation, Single-Center, Phase 1 Clinical Trial to Evaluate Tolerability, Safety, and Exploratory Efficacy of ATORM-C in Patients With Crohn's Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This Phase 1 study evaluates the safety and tolerability of ATORM-C in patients with Crohn's disease. ATORM-C is an investigational product consisting of autologous adult stem cell-derived intestinal organoids. Participants will receive a single dose of ATORM-C applied directly to a target intestinal ulcer during colonoscopy. The study will also explore the effect of ATORM-C on intestinal ulcer healing.
详细描述
This is an open-label, sequential dose-escalation Phase 1 study to evaluate the safety, tolerability, and exploratory efficacy of ATORM-C across three dose levels in patients with Crohn's disease. ATORM-C is manufactured by culturing and expanding autologous adult stem cell-derived intestinal organoids isolated from each participant's intestinal tissue. Participants will receive a single administration of ATORM-C directly applied to a target intestinal ulcer during colonoscopy. Primary evaluations will focus on safety and tolerability, with exploratory assessments of ATORM-C's effect on intestinal ulcer healing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 19 years or older and younger than 80 years at the time of screening (male or female).
- •Diagnosed with Crohn's disease at least 6 months prior to screening, confirmed by imaging, tissue sampling (biopsy), and/or colonoscopy.
- •Have had an inadequate response to at least 6 months of standard treatment for Crohn's disease (such as anti-inflammatory drugs, oral corticosteroids, immunosuppressants, or biologic agents). Inadequate response means failure to achieve ulcer-free endoscopy, defined as an SES-CD Ulcerated Surface Score of 0 or
- •Have active daily symptoms at screening and right before treatment, defined as either an average of 4 or more loose/liquid stools per day or an average daily abdominal pain score of 2 or more, based on the corresponding CDAI components.
- •Meet all of the following colonoscopy findings at screening:
- •Have at least one active ulcer in an accessible area of the intestine (such as the colon or ileocecal region).
- •Have at least one ulcer with a longest diameter of 5 mm or larger.
- •Have an active ulcer segment with an endoscopic severity score (SES-CD) of 6 or higher, with an ulcer size score of 2 or higher and no narrowing or blockage (stricture score of 0) in that area.
- •Meet all required blood test standards for cell therapy donor eligibility.
- •Voluntarily agree to participate and sign the written informed consent form after receiving a full explanation of the study.
排除标准
- •Other Inflammatory Bowel Conditions: Diagnosed with ulcerative colitis or unclassified colitis.
- •Surgical Needs: Require, or are expected to require, surgery for Crohn's disease or its complications.
- •Severe Co-existing Conditions: Have a severe autoimmune disease other than Crohn's disease, or an active abdominal/perianal condition (such as an undrained abscess or active fistula).
- •Recent Surgeries: Had bowel resection within 6 months or intra-abdominal surgery within 3 months prior to screening.
- •Procedure Inability: Unable to safely undergo bowel preparation, colonoscopy, or sedation, or have a known allergy/contraindication to medications used during these procedures.
- •Uncontrolled Medical Issues: Have a clinically significant or poorly controlled medical condition, such as severe heart, bleeding, kidney, or liver disease, or uncontrolled diabetes.
- •Active Severe Infection: Have an active, severe infection requiring ongoing medical treatment.
- •Cancer History: Have a history of cancer (malignancy) within 5 years before screening, except for specific low-risk cancers permitted by the protocol.
- •Allergies to Study Treatment: Have a known severe allergy (hypersensitivity) to ATORM-C, its ingredients, or materials used in its manufacturing.
- •Prohibited Therapies or Transplants: Are taking prohibited medications, have previously received any cell therapy product, or have received an organ transplant (except corneal transplant).
- •Significant Blood Test Abnormalities: Have severe laboratory test abnormalities, including liver function (AST or ALT ≥3 times the upper limit of normal), kidney function (eGFR <30 mL/min/1.73 m²), bleeding markers (PT INR >1.5), or low blood platelets (<50,000/mm³).
- •Pregnancy, Breastfeeding, or Contraception: Are pregnant, breastfeeding, or unwilling to follow the protocol-specified contraception requirements during the study.
- •Recent Clinical Trials: Received another investigational drug or device within 4 weeks prior to screening.
- •Investigator Judgment: Deemed unsuitable for participation by the study investigator for any other safety reason.
研究组 & 干预措施
Low-Dose ATORM-C
16,330 organoids (0.2 mL) per cm² of ulcer area
干预措施: Autologous Adult Stem Cell-Derived Intestinal Organoid (Biological)
Medium-Dose ATORM-C
81,650 organoids (0.2 mL) per cm² of ulcer area
干预措施: Autologous Adult Stem Cell-Derived Intestinal Organoid (Biological)
High-Dose ATORM-C
163,300 organoids (0.2 mL) per cm² of ulcer area
干预措施: Autologous Adult Stem Cell-Derived Intestinal Organoid (Biological)
结局指标
主要结局
Dose-Limiting Toxicities (DLTs)
时间窗: From ATORM-C administration through 4 weeks post-dose
Occurrence of dose-limiting toxicities (DLTs). A DLT is defined as any Grade 3 or higher adverse reaction according to NCI CTCAE v5.0 that is assessed as possibly, probably, or certainly related to ATORM-C. CTCAE grades range from Grade 1 (mild) to Grade 5 (death related to an adverse event), with higher grades indicating greater severity.
Determination of Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
时间窗: From ATORM-C administration through 24 weeks post-dose
The MTD and RP2D of ATORM-C will be determined based on the occurrence of dose-limiting toxicities (DLTs) during the dose-escalation period and the overall safety and tolerability of ATORM-C.
次要结局
- Incidence of Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)(From ATORM-C administration through 24 weeks post-dose)
- Changes in Clinical Laboratory Tests, Vital Signs, Physical Examinations, and 12-Lead Electrocardiograms (ECGs)(Baseline through 24 weeks post-dose, at protocol-specified visits)
- Change from Baseline in Target Ulcer Size(Baseline and Weeks 4, 12, and 24 post-dose)
- Change from Baseline in Modified Global Histologic Disease Activity Score (Modified GHAS) of the Target Ulcer(Baseline and Week 24 post-dose)
- Change from Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) of the Target Ulcer(Baseline and Weeks 4, 12, and 24 post-dose)
- Proportion of Participants Achieving ≥50% Reduction from Baseline in SES-CD Score of the Target Ulcer(Baseline and Week 24 post-dose)
- Proportion of Participants Achieving Endoscopic Remission of the Target Ulcer(Baseline and Weeks 4, 12, and 24 post-dose)