Allogeneic faecal microbiota, pooled for Axial spondyloarthritis

Inclusion criteria

• {"criterion_text":"- Adult patient (age 18 to 75 years old) with SpA diagnosed for at least 6 months at the time of inclusion, meeting the ASAS classification criteria for axial SpA, with presence of radiographic sacro-illitis (ankylosing spondylitis) or not\n- Patient suffering of active SpA, with or without current treatment, having a BASDAI score ≥ 4 (0-10) and a score of back pain ≥ 4 (0-10) despite optimal drug management for at least 6 months including at least 2 different NSAIDs at the maximum tolerated dose for at least 2 months (or less in case of intolerance or contra-indication) and at least a first line of biotherapy (anti-TNFα or anti-IL-17) or JAK inhibitor for at least 4 months (or less in case of intolerance or contra-indication)\n- Subjects are allowed to continue oral NSAID, oral and/or subcutaneus methotrexate (≤ 25 mg/week) and/or oral hydroxychloroquine (≤ 400 mg/day) and/or oral corticosteroid (≤ 10 mg/day of prednisone), as long as these treatments have remained at stable dose (i.e. inchanged dose) for 4 weeks prior to inclusion\n- Subjects are allowed to continue anti-TNFα, anti-IL-17 or JAK inhibitor therapies, as long as these treatments have remained at stable dose for 3 months prior to inclusion\n- Women of childbearing potential with efficient contraceptive protection at the inclusion and during at least the interventional phase (D168)\n- Patient with health insurance (AME except)\n- Patient is willing to provide written informed consent prior to enrolment and agrees to follow the protocol"}

Exclusion criteria

• {"criterion_text":"- Patient under legal protection (guardianship or curatorship)\n- Patients with unstable severe condition other than axial SpA on that could jeopardize treatment procedure or evaluation according to the investigator's assessment\n- Previous FMT treatment\n- Contra-indication to colon preparation (Moviprep® or Moviprep orange®) according to SmPC\n- Current or past evidence of bowel obstruction\n- Confirmed or suspected intestinal ischemia\n- Confirmed or suspected toxic megacolon or gastrointestinal perforation\n- Extended colectomy (> two-thirds of colon)\n- Any gastro-intestinal bleeding in the past 3 months before inclusion\n- Any history of gastro-intestinal surgery in the past 3 months before inclusion\n- Severe organ dysfunction\n- Subject who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development\n- Any contra-indication to swallow capsules\n- Known allergy or intolerance to IMP and / or excipients according to Investigator’s Brochure\n- Lack of access to a refrigerator to store the medication (MaaT033® or MaaT030®)\n- Concomitant participation in another interventional clinical trial\n- Pregnant or breastfeeding woman\n- Patient with IBD in active state, according to the judgment of the Investigator\n- Corticosteroid injection within 4 weeks before inclusion\n- Active infection according to the judgment of the Investigator\n- Any antibiotic (including Sulfasalazin) or antifungal treatment within 4 weeks before inclusion\n- Probiotics intake within 4 weeks before inclusion\n- Known infection with Clostridium difficile or Escherichia coli within 10 days before inclusion"}

Primary endpoints

• {"endpoint_text":"- Two co-primary endpoints, in a hierarchical design: 1. Variation of MSP between baseline and D42, 2. The proportion of patients satisfying ASAS 20 improvement criteria at D42, by randomisation group","definition_or_measurement_approach":"1. Variation of MSP between baseline and D42 — measured as change in MSP (microbial species/pangenome) richness/variation between baseline and day 42; 2. Proportion of patients satisfying ASAS20 improvement criteria at D42 — assessed using standard ASAS20 criteria at day 42 by randomisation group."}

Secondary endpoints

• {"endpoint_text":"- A superior efficacy of FMT over placebo to correct dysbiosis at D42, defined by an increase in OTU richness in the FMT group, superior to variation in the placebo group","definition_or_measurement_approach":"Measured as increase in OTU richness (microbial diversity) at D42 in FMT versus placebo."}
• {"endpoint_text":"- A correction of dysbiotic fecal microbiota at D28, D84 and D168 in FMT-treated group defined by an average increase of at least 65 MSP as compared to baseline (D0)","definition_or_measurement_approach":"Measured as average increase of at least 65 MSP (microbial species/pangenome) at D28, D84 and D168 versus baseline in FMT group."}
• {"endpoint_text":"- A superior efficacy of FMT over placebo to correct dysbiosis at D28, D84 and D168 defined by an increase in MSP richness in the FMT group, superior to variation in the placebo group","definition_or_measurement_approach":"Measured as increase in MSP richness at specified timepoints comparing FMT versus placebo."}
• {"endpoint_text":"- A clinical improvement during the 168 days follow-up after FMT defined by a greater proportion of patients satisfying ASAS20 improvement criteria as compared to baseline (D0), throughout this period in the FMT group, as compared to the placebo group","definition_or_measurement_approach":"Proportion of patients meeting ASAS20 improvement criteria at scheduled visits up to day 168 compared between arms."}
• {"endpoint_text":"- A clinical improvement during the 168 days follow-up after FMT defined by a greater proportion of patients satisfying ASAS40 improvement criteria as compared to baseline (D0), at D28, D42, D84 and D168 in the FMT group, as compared to the placebo group","definition_or_measurement_approach":"Proportion of patients meeting ASAS40 criteria at D28, D42, D84 and D168 compared between arms."}
• {"endpoint_text":"- A greater achievement of a partial remission according to the ASAS definition at D28, D42, D84 and D168 in the FMT group, as compared to the placebo group","definition_or_measurement_approach":"Proportion achieving ASAS partial remission (value <20 in each of 4 ASAS domains) at specified timepoints."}
• {"endpoint_text":"- An improvement of biological inflammation assessed by CRP levels variation, between baseline (D0) and D28, D42, D84 and D168 in the FMT group, as compared to the placebo group","definition_or_measurement_approach":"Change in CRP levels from baseline at D28, D42, D84 and D168 compared between arms."}
• {"endpoint_text":"- An improvement of ASDAS_CRP at D28, D42, D84 and D168, as compared to baseline (D0) greater in the FMT group, as compared to the placebo group","definition_or_measurement_approach":"Change in ASDAS-CRP score from baseline at listed timepoints comparing arms."}
• {"endpoint_text":"- An improvement of Bath Ankylosing Spondylitis Metrology Index (BASMI) at D28, D42, D84 and D168, as compared to baseline (D0) greater in the FMT group, as compared to the placebo group","definition_or_measurement_approach":"Change in BASMI score from baseline at specified visits compared between arms."}
• {"endpoint_text":"- An improvement of MASES at D28, D42, D84 and D168, as compared to baseline (D0) greater in the FMT group, as compared to the placebo group","definition_or_measurement_approach":"Change in MASES (Maastricht Ankylosing Spondylitis Enthesitis Score) from baseline at specified visits compared between arms."}
• {"endpoint_text":"- A decrease of non-steroidal anti-inflammatory drugs (NSAID) intake score at D28, D42, D84 and D168, as compared to baseline (D0) greater in the FMT group, as compared to the placebo group","definition_or_measurement_approach":"Change in NSAID intake score from baseline at listed timepoints compared between arms."}

France

Earliest CTIS Part Ii Submission Date

18-01-2024

Latest Decision Or Authorization Date

11-09-2025

Processing Time Days

602

Number Of Sites

1

Number Of Participants

25

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Contract research organisations

Name

Euromed Pharma

Responsibilities

Designated/mandated by partner MaaT Pharma for packaging and labelling of treatment units / supply chain (mentioned in serious breach description)

Third parties

• {"country":"","full_name":"Fondation Arthritis & Clarins Worldwide 2016 (private charity organization)","duties_or_roles":"Source of monetary support","organisation_type":"Private charity organization"}
• {"country":"","full_name":"MAAT PHARMA","duties_or_roles":"Manufacturer/supplier of MaaT033 investigational product; partner for product provision","organisation_type":""}
• {"country":"","full_name":"NORGINE","duties_or_roles":"Supplier/manufacturer of MOVIPREP colon preparation used as auxiliary product","organisation_type":""}