Crohn's Disease, Crohn's Diseases
Conditions
Keywords
Crohn Disease, Intestinal Organoid, Autologous Organoid, Intestinal Ulcer, ATORM-C, Autologous Adult Stem Cell-Derived Intestinal Organoid, Dose Escalation, Crohn's disease
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALAutologous Adult Stem Cell-Derived Intestinal Organoid
ATORM-C is an investigational product consisting of autologous adult stem cell-derived intestinal organoids. Participants will receive a single administration of ATORM-C applied directly to the target intestinal ulcer during colonoscopy. ATORM-C is administered with fibrin glue (Greenplast-Q) to facilitate local application to the target ulcer.
Sponsors
ORGANOIDSCIENCES LTD.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A standard 3+3 sequential dose-escalation design with three dose levels of ATORM-C. Dose escalation will be based on the occurrence of dose-limiting toxicities (DLTs) in the preceding cohort.
Eligibility
Sex/Gender
ALL
Age
19 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 19 years or older and younger than 80 years at the time of screening (male or female). 2. Diagnosed with Crohn's disease at least 6 months prior to screening, confirmed by imaging, tissue sampling (biopsy), and/or colonoscopy. 3. 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 1. 4. 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. 5. 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. 6. Meet all required blood test standards for cell therapy donor eligibility. 7. Voluntarily agree to participate and sign the written informed consent form after receiving a full explanation of the study.
Exclusion criteria
1. Other Inflammatory Bowel Conditions: Diagnosed with ulcerative colitis or unclassified colitis. 2. Surgical Needs: Require, or are expected to require, surgery for Crohn's disease or its complications. 3. 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). 4. Recent Surgeries: Had bowel resection within 6 months or intra-abdominal surgery within 3 months prior to screening. 5. Procedure Inability: Unable to safely undergo bowel preparation, colonoscopy, or sedation, or have a known allergy/contraindication to medications used during these procedures. 6. Uncontrolled Medical Issues: Have a clinically significant or poorly controlled medical condition, such as severe heart, bleeding, kidney, or liver disease, or uncontrolled diabetes. 7. Active Severe Infection: Have an active, severe infection requiring ongoing medical treatment. 8. Cancer History: Have a history of cancer (malignancy) within 5 years before screening, except for specific low-risk cancers permitted by the protocol. 9. Allergies to Study Treatment: Have a known severe allergy (hypersensitivity) to ATORM-C, its ingredients, or materials used in its manufacturing. 10. Prohibited Therapies or Transplants: Are taking prohibited medications, have previously received any cell therapy product, or have received an organ transplant (except corneal transplant). 11. 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). 12. Pregnancy, Breastfeeding, or Contraception: Are pregnant, breastfeeding, or unwilling to follow the protocol-specified contraception requirements during the study. 13. Recent Clinical Trials: Received another investigational drug or device within 4 weeks prior to screening. 14. Investigator Judgment: Deemed unsuitable for participation by the study investigator for any other safety reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Limiting Toxicities (DLTs) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) | From ATORM-C administration through 24 weeks post-dose | Occurrence of treatment-emergent adverse events (TEAEs), adverse drug reactions (ADRs), serious adverse events (SAEs), serious adverse drug reactions (SADRs), adverse events of special interest (AESIs), and administration site local adverse events. Adverse events leading to discontinuation of study treatment or death will also be evaluated. |
| Changes in Clinical Laboratory Tests, Vital Signs, Physical Examinations, and 12-Lead Electrocardiograms (ECGs) | Baseline through 24 weeks post-dose, at protocol-specified visits | Changes from baseline in continuous safety parameters, including clinical laboratory tests and vital signs, evaluated at protocol-specified visits. Occurrence of clinically significant abnormalities (Abnormal CS) in clinical laboratory tests, physical examinations, and 12-lead electrocardiograms (ECGs) post-dose will also be evaluated. |
| Change from Baseline in Target Ulcer Size | Baseline and Weeks 4, 12, and 24 post-dose | Absolute change and percentage change from baseline in the size of the target ulcer, evaluated based on the longest diameter, shortest diameter, and total surface area measured during colonoscopy at protocol-specified time points. |
| 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 the Modified Global Histologic Disease Activity Score (Modified GHAS) based on histologic evaluation of mucosal biopsy specimens collected from the target ulcer. The regional Modified GHAS ranges from 0 to 12, with higher scores indicating greater histologic disease activity. |
| 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 | Change from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD) total score and ulcer size subscore evaluated specifically for the target ulcer via colonoscopy. The SES-CD assessed for the target ulcer evaluates 4 endoscopic variables, each scored from 0 to 3, yielding a target ulcer regional score ranging from 0 to 12. Higher scores indicate greater endoscopic disease activity. |
| Proportion of Participants Achieving ≥50% Reduction from Baseline in SES-CD Score of the Target Ulcer | Baseline and Week 24 post-dose | Percentage of participants who achieve a 50% or greater reduction from baseline in the Simple Endoscopic Score for Crohn's Disease (SES-CD) total score for the target ulcer at Week 24 post-dose. The regional target ulcer SES-CD ranges from 0 to 12, with higher scores indicating greater endoscopic disease activity. |
| Proportion of Participants Achieving Endoscopic Remission of the Target Ulcer | Baseline and Weeks 4, 12, and 24 post-dose | Percentage of participants achieving endoscopic remission of the target ulcer at Week 24 post-dose. Endoscopic remission is defined as a Simple Endoscopic Score for Crohn's Disease (SES-CD) total score of less than 2 (\<2) for the target ulcer. The regional target ulcer SES-CD ranges from 0 to 12, with higher scores indicating greater endoscopic disease activity. |
Countries
South Korea
Outcome results
None listed