EXL01 in the Maintenance of Steroid-induced Clinical Response/Remission in Participants With Mild to Moderate Crohn's Disease (MAINTAIN)

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

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).

Study Overview

• Status: Terminated
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: EXL01; Other: SoC corticosteroid - Induction Period; Other: SoC corticosteroid - Tapering; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Liège, Belgium, 4000
    • CHU de Liege
• Poland
  • Lublin, Poland, 20582
    • Zespół Poradni Specjalistycznych REUMED
  • Rzeszów, Poland, 35-326
    • Centrum Medyczne "Medyk" Sp. zo.o. Sp.K
  • Sopot, Poland, 81-756
    • Endoskopia Sp. z o. o., Ul. B.Chrobrego 6/8
  • Wrocław, Poland, 52-210
    • PlanetMed Sp.z.o.o. Gastroenterology, Ul.Lubinowa 12/8

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A (Open-Label EXL01 Maintenance Therapy); Oral EXL01 once daily for up to 24 weeks (after SoC corticosteroid induction therapy).	Drug: EXL01; Oral EXL01 once daily for up to 24 weeks (after SoC corticosteroid induction therapy).; Other Names: Faecalibacterium prausnitzii EXL01-strain; Other: SoC corticosteroid - Induction Period; Oral prednisone 40 mg or budesonide 9 mg once daily for 3 to 7 weeks, as assigned by the investigator; Other: SoC 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.
Experimental: Part B (EXL01 Maintenance Therapy); Oral EXL01 once daily for up to 24 weeks (after SoC corticosteroid induction therapy).	Drug: EXL01; Oral EXL01 once daily for up to 24 weeks (after SoC corticosteroid induction therapy).; Other Names: Faecalibacterium prausnitzii EXL01-strain; Other: SoC corticosteroid - Induction Period; Oral prednisone 40 mg or budesonide 9 mg once daily for 3 to 7 weeks, as assigned by the investigator; Other: SoC 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.
Placebo Comparator: Part B (Placebo Maintenance Therapy); Oral EXL01 matched placebo once daily for up to 24 weeks (after SoC corticosteroid induction therapy).	Other: SoC corticosteroid - Induction Period; Oral prednisone 40 mg or budesonide 9 mg once daily for 3 to 7 weeks, as assigned by the investigator; Other: SoC 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.; Drug: Placebo; Oral EXL01 matching placebo once daily for up to 24 weeks (after SoC corticosteroid induction therapy).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The systemic and intestinal safety and tolerability of orally administered EXL01	Number of participants with adverse events (AE[s]). Number of participants with treatment discontinuations due to an AE. AEs assessed by CTCAE v5.0	Up to 43 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants in steroid-free clinical remission at Week 24	Endpoints: Crohn's disease activity index (CDAI) score (higher scores indicate more active/severe disease) and use of corticosteroids	Maintenance Period Week 24
Proportion of participants in steroid-free clinical remission and mucosal healing at 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	Maintenance Period Week 24
Proportion of participants in steroid free clinical remission and mucosal healing and normal inflammatory markers at 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	Maintenance Period Week 24
Proportion of participants with an endoscopic response at Week 24	Endpoint: SES-CD score	Maintenance Period Week 24
Time to clinical relapse in participants with CD treated with EXL01 to participants treated with placebo (Part B only)	Time to clinical relapse, defined as the time from first dose of EXL01 or placebo to first documented clinical relapse (Part B only)	Maintenance Period Baseline to Week 24
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)	This is a composite measure. Endpoints: SES-CD score, Robarts Histopathology Index score (measures histological disease activity; higher scores indicate more severe disease activity)	Maintenance Period Baseline to Week 24
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)	This is a composite measure. 16S sequencing / shotgun metagenomics and specific quantitative polymerase chain reaction (qPCR)/digital droplet (dd)PCR	Maintenance Period Baseline to Week 24

Collaborators and Investigators

• Sponsor: Exeliom Biosciences
• Collaborators: Alimentiv Inc.
• Investigators: Study Director: Acting Chief Medical Officer, Exeliom Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2023
• Primary Completion (Actual): October 2, 2024
• Study Completion (Actual): October 2, 2024

Study Registration Dates

• First Submitted: September 2, 2022
• First Submitted That Met QC Criteria: September 13, 2022
• First Posted (Actual): September 15, 2022

Study Record Updates

• Last Update Posted (Actual): October 10, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Microbiota; Inflammatory Bowel Disease; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colonic Diseases; Faecalibacterium prausnitzii; Crohn Disease, remission
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: EXL01-CD-001; 2021-003432-81 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No