MAINTAIN-POP: EXL01 and prevention of post-operative recurrence of Crohn's disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Groupe De Recherche Sur Les Maladies Inflammatoires Digestives

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

31 Mar 2025 → ongoing

Decision date (initial)

2025-01-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To compare the distribution of endoscopic modified Rutgeerts scores, as centrally assessed, at 6 months post-surgery in patients with CD treated with EXL01 to patients treated with placebo

Secondary objectives 10

1. To evaluate the impact of EXL01 treatment on severe endoscopic recurrence, according to modified Rutgeerts score (mRS) as centrally assessed, at 6 months post-surgery.
2. To compare time to clinical relapse in patients with CD treated with EXL01 to patients treated with placebo
3. To compare disease related symptoms and inflammatory markers post-surgery in patients with CD treated with EXL01 to patients treated with placebo
4. To compare the endoscopic disease activity, using SES-CD score in patients with CD treated with EXL01 to patients treated with placebo.
5. To analyze histological inflammation in the neoterminal ileum in patients with CD treated with EXL01 to patients treated with placebo (central assessment)
6. To compare the evolution of the faecal- and mucosa-associated microbiota (ileal and colonic) in patients with CD treated with EXL01 to patients treated with placebo
7. To evaluate change from baseline in health-related quality of life (HRQoL) measures in participants with CD treated with/without EXL01 post-surgery. To assess: . Global health status and wellbeing using Short-form-36 (SF-36) questionnaire . Bowel disease-related QoL using Inflammatory Bowel Disease Questionnaire (IBDQ) questionnaire.
8. To evaluate the impact of EXL01 treatment on endoscopic remission, according to modified Rutgeerts score as centrally assessed, at 6 months post-surgery
9. To evaluate the safety and tolerability of orally administered EXL01 post-surgery in participants with CD
10. To evaluate the impact of EXL01 treatment on endoscopic recurrence, according to modified Rutgeerts score as centrally assessed at 6 months post-surgery

Conditions and MedDRA coding

Crohn's disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Is male or female aged ≥18 years at the time of providing documented informed consent.
2. 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.
3. Has undergone an ileocecal resection or iterative ileo-colonic resection, as per institutional SoC, between 5 days to 5 weeks before randomization.
4. Is scheduled, in SoC context, to receive no treatment for CD or a biotherapy treatment in the 6 months after surgery

Exclusion criteria 8

1. Has a not recovered adequately from any toxicity and/or complications from the surgery before the first dose of study intervention
2. Has a current stoma. Inclusion will be possible after continuity restoration (during the 5 weeks following continuity restoration)
3. Has active anal fistula
4. Is scheduled to receive an anti-JAK treatment in the 6 months after surgery
5. Has had more than 2 past small bowel resections or cumulated intestinal resection superior to 100 cm
6. Has a contraindication to endoscopy or anaesthesia.
7. 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.
8. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 10

1. 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.
2. 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.
3. Mean values and changed from baseline at Weeks 4, 12 and 24/EOT: • Crohn’s Disease Activity Index (CDAI) overall score • 2-item Patient-Reported Outcome Measure (PRO-2) overall score and subscale scores (stool frequency, abdominal pain, rectal bleeding) • Serum C-reactive protein (CRP) levels • Faecal calprotectin levels
4. SES-CD score (global score and score per GI segment) at Week 24/EOT, evaluated by endoscopy with video capture, and assessed by BICR.
5. RHI score and Geboes score, at Week 24/EOT, evaluated from histopathology images, marked to identify the segment biopsied and assessed by BICR
6. . 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
7. 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)
8. Endoscopic remission of CD at Week 24/EOT, defined as mRSI = i0, evaluated by endoscopy with video capture and assessed by BICR.
9. . AEs (incidence and severity) . Discontinuing study treatment due to an AE
10. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe De Recherche Sur Les Maladies Inflammatoires Digestives

Sponsor organisation

Groupe De Recherche Sur Les Maladies Inflammatoires Digestives

Address

1 Avenue Claude Vellefaux

City

Paris

Postcode

75010

Country

France

Scientific contact point

Organisation

Groupe De Recherche Sur Les Maladies Inflammatoires Digestives

Contact name

Matthieu ALLEZ

Public contact point

Organisation

Groupe De Recherche Sur Les Maladies Inflammatoires Digestives

Contact name

Madeleine BEZAULT

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications