Clinical trial NCT05542355: EXL01 in the Maintenance of Steroid-induced Clinical Response/Remission in Participants With Mild to Moderate Crohn's Disease
Official title: A Phase 1, Multicentre, 2-Part, Randomised, Parallel-arm, Placebo-controlled, Partially Double-blind Study to Evaluate the Safety and Target Engagement of EXL01 in the Maintenance of Steroid-induced Clinical Response or Remission in Participants With Mild to Moderate Crohn's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Crohn Disease
Keywords: Gastrointestinal Diseases
Inflammatory Bowel Disease
Colonic Diseases
Intestinal Diseases
Digestive System Diseases
Microbiota
Crohn Disease, remission
Faecalibacterium prausnitzii
Lead sponsor: Exeliom Biosciences
Sponsor class: INDUSTRY
Collaborators: name: Alimentiv Inc.
First posted: 2022-09-15
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part A = Single Arm open label. Part B = Randomised, placebo-controlled, double-blind.
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: The systemic and intestinal safety and tolerability of orally administered EXL01
timeFrame: Up to 43 weeks
Secondary outcomes:
measure: Proportion of participants in steroid-free clinical remission at Week 24
timeFrame: Maintenance Period Week 24
measure: Proportion of participants in steroid-free clinical remission and mucosal healing at Week 24
timeFrame: Maintenance Period Week 24
measure: Proportion of participants in steroid free clinical remission and mucosal healing and normal inflammatory markers at Week 24
timeFrame: Maintenance Period Week 24
measure: Proportion of participants with an endoscopic response at Week 24
timeFrame: Maintenance Period Week 24
measure: Time to clinical relapse in participants with CD treated with EXL01 to participants treated with placebo (Part B only)
timeFrame: Maintenance Period Baseline to Week 24
measure: 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)
timeFrame: Maintenance Period Baseline to Week 24
measure: 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)
timeFrame: Maintenance Period Baseline to Week 24
Other outcomes:
Locations:
city: Liège
country: Belgium
facility: CHU de Liege
city: Lublin
country: Poland
facility: Zespół Poradni Specjalistycznych REUMED
city: Rzeszów
country: Poland
facility: Centrum Medyczne "Medyk" Sp. zo.o. Sp.K
city: Sopot
country: Poland
facility: Endoskopia Sp. z o. o., Ul. B.Chrobrego 6/8
city: Wrocław
country: Poland
facility: PlanetMed Sp.z.o.o. Gastroenterology, Ul.Lubinowa 12/8
Study officials:
affiliation: Exeliom Biosciences
name: Acting Chief Medical Officer
role: STUDY_DIRECTOR
References: