Crohn Disease
Conditions
Keywords
Gastrointestinal Diseases, Inflammatory Bowel Disease, Colonic Diseases, Intestinal Diseases, Digestive System Diseases, Microbiota, Crohn Disease, remission, Faecalibacterium prausnitzii
Brief summary
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).
Detailed description
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.
Interventions
DRUGEXL01
Oral EXL01 once daily for up to 24 weeks (after SoC corticosteroid induction therapy).
DRUGPlacebo
Oral EXL01 matching placebo once daily for up to 24 weeks (after SoC corticosteroid induction therapy).
OTHERSoC corticosteroid - Induction Period
Oral prednisone 40 mg or budesonide 9 mg once daily for 3 to 7 weeks, as assigned by the investigator
OTHERSoC corticosteroid - Tapering
Same product as the Induction Period. Oral prednisone: 30 mg for 1 week, 25 mg for 1 week, 20 mg for 1 week, 15 mg for 1 week, 10 mg for 1 week, 5 mg for 1 week and stop. OR Oral budesonide: 6 mg for 3 weeks, 3 mg for 3 weeks, stop.
Sponsors
Alimentiv Inc.
Exeliom Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Part A: None (Open-label). Part B: Double-blind.
Intervention model description
Part A = Single Arm open label. Part B = Randomised, placebo-controlled, double-blind.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 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 \<350. * Part B only: Active mucosal inflammation. Key
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The systemic and intestinal safety and tolerability of orally administered EXL01 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants in steroid-free clinical remission and mucosal healing at Week 24 | Maintenance Period Week 24 | This is a composite measure. Endpoints: CDAI score, simple endoscopic score for Crohn's Disease (SES-CD; higher scores indicate more severe disease), and use of corticosteroids |
| Proportion of participants in steroid free clinical remission and mucosal healing and normal inflammatory markers at Week 24 | Maintenance Period Week 24 | This is a composite measure. Endpoints: CDAI score, SES-CD score, C-reactive protein (CRP) level (a marker of inflammation), faecal calprotectin level (a marker of intestinal inflammation), and use of corticosteroids |
| Proportion of participants with an endoscopic response at Week 24 | Maintenance Period Week 24 | Endpoint: SES-CD score |
| Proportion of participants in steroid-free clinical remission at Week 24 | Maintenance Period Week 24 | Endpoints: Crohn's disease activity index (CDAI) score (higher scores indicate more active/severe disease) and use of corticosteroids |
| 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 | This is a composite measure. Endpoints: SES-CD score, Robarts Histopathology Index score (measures histological disease activity; higher scores indicate more severe disease activity) |
| 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 | This is a composite measure. 16S sequencing / shotgun metagenomics and specific quantitative polymerase chain reaction (qPCR)/digital droplet (dd)PCR |
| 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 | Time to clinical relapse, defined as the time from first dose of EXL01 or placebo to first documented clinical relapse (Part B only) |
Countries
Belgium, Poland
Outcome results
None listed