EXL01 for Crohn's disease

Inclusion criteria

• {"criterion_text":"- Is male or female aged ≥18 years at the time of providing documented informed consent."}
• {"criterion_text":"- Has a diagnosis of CD with ileal involvement (ileal only or ileocolonic; L1 or L3 in Montreal classification) for at least 3 months prior to Screening."}
• {"criterion_text":"- Has undergone an ileocecal resection or iterative ileo-colonic resection, as per institutional SoC, between 5 days to 5 weeks before randomization."}
• {"criterion_text":"- Is scheduled, in SoC context, to receive no treatment for CD or a biotherapy treatment in the 6 months after surgery"}

Exclusion criteria

• {"criterion_text":"- Has a not recovered adequately from any toxicity and/or complications from the surgery before the first dose of study intervention"}
• {"criterion_text":"- Has a current stoma. Inclusion will be possible after continuity restoration (during the 5 weeks following continuity restoration)"}
• {"criterion_text":"- Has active anal fistula"}
• {"criterion_text":"- Is scheduled to receive an anti-JAK treatment in the 6 months after surgery"}
• {"criterion_text":"- Has had more than 2 past small bowel resections or cumulated intestinal resection superior to 100 cm"}
• {"criterion_text":"- Has a contraindication to endoscopy or anaesthesia."}
• {"criterion_text":"- Is receiving antibiotics at time of randomization or is likely to require antibiotic treatment within 6 weeks of the first dose of EXL01 or placebo."}
• {"criterion_text":"- Has a history of hypersensitivity to EXL01 and/or any excipients, which are listed in the IB, and/or to soybean or soy-containing products."}

Primary endpoints

• {"endpoint_text":"- The distribution of modified Rutgeerts score grouped in 4 categories (i0, i1 - i2a, i2b, i3 - i4) at Week 24/EOT, evaluated by endoscopy with video capture, and assessed by BICR","definition_or_measurement_approach":"Evaluated by endoscopy with video capture and assessed by blinded independent central review (BICR); grouped in 4 mRS categories (i0, i1 - i2a, i2b, i3 - i4) at Week 24/End of Treatment."}

Secondary endpoints

• {"endpoint_text":"- Severe endoscopic recurrence at Week 24/EOT, defined as mRSI equal to i3 or i4, evaluated by endoscopy with video capture, and assessed by BICR.","definition_or_measurement_approach":"Defined as modified Rutgeerts score (mRSI) equal to i3 or i4; evaluated by endoscopy with video capture and assessed by BICR at Week 24/EOT."}
• {"endpoint_text":"- Time to clinical relapse, defined as the time from the first dose of study treatment to first documented clinical relapse (confirmed by endoscopy or imaging procedure and assessed by BICR) The analysis will include all randomised participants as randomised who have a confirmed clinical relapse, regardless of whether the participant withdraws from therapy.","definition_or_measurement_approach":"Time (from first dose) to first documented clinical relapse; relapse confirmation by endoscopy or imaging and assessed by BICR; analysis includes all randomized participants with confirmed relapse."}
• {"endpoint_text":"- Mean values and changed from baseline at Weeks 4, 12 and 24/EOT: •\tCrohn’s Disease Activity Index (CDAI) overall score •\t2-item Patient-Reported Outcome Measure (PRO-2) overall score and subscale scores (stool frequency, abdominal pain, rectal bleeding) •\tSerum C-reactive protein (CRP) levels •\tFaecal calprotectin levels","definition_or_measurement_approach":"Mean and change from baseline at Weeks 4, 12, and 24/EOT for CDAI, PRO-2 (and subscales), serum CRP, and fecal calprotectin."}
• {"endpoint_text":"- SES-CD score (global score and score per GI segment) at Week 24/EOT, evaluated by endoscopy with video capture, and assessed by BICR.","definition_or_measurement_approach":"SES-CD global and per-segment scores assessed by endoscopy with video capture and BICR at Week 24/EOT."}
• {"endpoint_text":"- RHI score and Geboes score, at Week 24/EOT, evaluated from histopathology images, marked to identify the segment biopsied and assessed by BICR","definition_or_measurement_approach":"Histopathology-derived RHI and Geboes scores from biopsy images at Week 24/EOT, segment identified and assessed by BICR."}
• {"endpoint_text":"- . 16S sequencing / shotgun metagenomics in faecal samples at various timepoints . 16S sequencing / shotgun metagenomics in tissue samples at Week 24/EOT . Levels, abundance and change from baseline in F. prausnitzii in faecal samples at various timepoints using qPCR/ddPCR . Levels of F. prausnitzii in biopsy samples at Week 24/EOT, using F. prausnitzii specific qPCR/ddPCR","definition_or_measurement_approach":"Microbiome analyses: 16S sequencing/shotgun metagenomics in fecal (various timepoints) and tissue (Week 24/EOT); quantification of F. prausnitzii by qPCR/ddPCR in fecal samples (various timepoints) and in biopsy samples at Week 24/EOT."}
• {"endpoint_text":"- Mean scores and change from baseline overtime in: . SF-36 overall score and 8 health domain scores . IBDQ overall score and subscale scores (bowel symptoms, systemic symptoms, emotional function, and social function)","definition_or_measurement_approach":"Mean and change from baseline over time for SF-36 overall and domain scores, and IBDQ overall and subscale scores."}
• {"endpoint_text":"- Endoscopic remission of CD at Week 24/EOT, defined as mRSI = i0, evaluated by endoscopy with video capture and assessed by BICR.","definition_or_measurement_approach":"Endoscopic remission defined as modified Rutgeerts score i0; evaluated by endoscopy with video capture and assessed by BICR at Week 24/EOT."}
• {"endpoint_text":"- . AEs (incidence and severity) . Discontinuing study treatment due to an AE","definition_or_measurement_approach":"Safety endpoints: incidence and severity of adverse events; discontinuations due to AEs as recorded during study."}
• {"endpoint_text":"- Endoscopic recurrence at Week 24/EOT, defined as a modified Rutgeerts score equal or superior to i2b (mRSI ≥ i2b), evaluated by endoscopy with video capture, and assessed by BICR","definition_or_measurement_approach":"Endoscopic recurrence defined as mRSI ≥ i2b; evaluated by endoscopy with video capture and assessed by BICR at Week 24/EOT."}

France

Earliest CTIS Part Ii Submission Date

03-12-2024

Latest Decision Or Authorization Date

26-03-2026

Processing Time Days

478

Number Of Sites

13

Number Of Participants

80

Primary sponsor

Full Name

Groupe De Recherche Sur Les Maladies Inflammatoires Digestives

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France