A Phase 1 Study of ATORM-C in Patients With Crohn's Disease
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age19-80
SponsorORGANOIDSCIENCES LTD.
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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 1.
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.
Disqualifiers
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.
Trial design
Design model
Sequential
Treatments tested in this trial
Autologous Adult Stem Cell-Derived Intestinal Organoid
Biological/VaccineATORM-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.
Treatment groups
18 Participants
are divided into 3 treatment groupsGroup A: Low-Dose ATORM-CExperimental treatment 1 intervention
Group B: Medium-Dose ATORM-CExperimental treatment 1 intervention
Group C: High-Dose ATORM-CExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Dose-Limiting Toxicities (DLTs)
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.
Time frame
From ATORM-C administration through 4 weeks post-dose2
Determination of Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)
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.
Time frame
From ATORM-C administration through 24 weeks post-doseSecondary outcomes
1
Incidence of Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)
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.
Time frame
From ATORM-C administration through 24 weeks post-dose2
Changes in Clinical Laboratory Tests, Vital Signs, Physical Examinations, and 12-Lead Electrocardiograms (ECGs)
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.
Time frame
Baseline through 24 weeks post-dose, at protocol-specified visits3
Change from Baseline in Target Ulcer Size
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.
Time frame
Baseline and Weeks 4, 12, and 24 post-dose4
Change from Baseline in Modified Global Histologic Disease Activity Score (Modified GHAS) of the Target Ulcer
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.
Time frame
Baseline and Week 24 post-doseOther outcomes
1
Proportion of Participants Achieving a ≥100-Point Reduction from Baseline in Crohn's Disease Activity Index (CDAI)
Percentage of participants who achieve a reduction of 100 points or greater (≥100 points) from baseline in the Crohn's Disease Activity Index (CDAI) total score at Week 24 post-dose. CDAI total scores range from 0 to over 600, with higher scores indicating greater disease activity. Frequencies and percentages will be summarized for each dose cohort and overall.
Time frame
Baseline and Week 24 post-dose2
Proportion of Participants Achieving Clinical Remission Based on Crohn's Disease Activity Index (CDAI)
Percentage of participants who achieve clinical remission, defined as a Crohn's Disease Activity Index (CDAI) total score of less than 150 (\<150) at protocol-specified time points post-dose. Higher CDAI scores indicate greater Crohn's disease activity.
Time frame
Weeks 4, 12, and 24 post-dose3
Proportion of Participants Achieving Clinical Response Based on Patient-Reported Outcomes (PRO2)
Percentage of participants who achieve a clinical response based on patient-reported outcomes (PRO2), defined as a reduction of 30% or greater (≥30%) from baseline in either the 7-day average Stool Frequency (SF) subscore or Abdominal Pain (AP) subscore, with neither subscore worsening from baseline. The SF subscore ranges from 0 to 11+ (higher scores reflect greater stool frequency), and the AP subscore ranges from 0 to 3 (higher scores indicate more severe pain).
Time frame
Baseline, and Weeks 4, 12, and 24 post-dose4
Proportion of Participants Achieving Clinical Remission Based on Patient-Reported Outcomes (PRO), Defined as SF ≤2.8 and AP ≤1.0
Percentage of participants who achieve clinical remission based on patient-reported outcomes (PRO2), defined as a 7-day average daily Stool Frequency (SF) of 2.8 or less (≤2.8) and a 7-day average Abdominal Pain (AP) score of 1.0 or less (≤1.0). Higher SF values indicate greater stool frequency, and higher AP scores indicate more severe abdominal pain.
Time frame
Weeks 4, 12, and 24 post-doseSponsors and contacts
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Source ClinicalTrials.gov