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

Sponsor

Exeliom Biosciences (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05542355

Collaborator

Alimentiv Inc. (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Crohn Disease	Drug: EXL01 Drug: Placebo Other: SoC corticosteroid - Induction Period Other: SoC corticosteroid - Tapering	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

67 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Part A = Single Arm open label. Part B = Randomised, placebo-controlled, double-blind.Part A = Single Arm open label. Part B = Randomised, placebo-controlled, double-blind.

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Part A: None (Open-label). Part B: Double-blind.

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Oct 1, 2025

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

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).	Drug: Placebo Oral EXL01 matching 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.

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

Placebo Comparator: Part B (Placebo Maintenance Therapy)

Oral EXL01 matched placebo once daily for up to 24 weeks (after SoC corticosteroid induction therapy).

Drug: Placebo

Oral EXL01 matching 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

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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
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
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)
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
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.
Received ≥2 prior biologic treatments for CD including infliximab, ustekinumab, vedolizumab, adalimumab, and certolizumab.
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.