The Efficacy of Fecal Microbiota Transplatation on Axial Spondyloarthritis Patients Resistant to Conventional Treatment

NCT05654753 | Recruiting Phase 2 DMC

• 2 other identifiers: APHP2209342023-504852-89-00
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Current pharmacological management of inflammatory rheumatism and in particular axial SpA remains imperfect. Only 50% of patients respond to the most effective biotherapies, and many of them are only partially relieved. In addition, these are extremely expensive treatments that expose them to the risk of potentially serious side effects. Compelling evidence indicates that gut dybiosis could be a critical trigger of inflammation in axial SpA and thus correcting dysbiosis represents an attractive way of reversing the pathogenic process.The efficacy of FMT in patients with axial SpA has never been studied. This randomized double-blind study will be the first to assess feasability of FMT in axial SpA, the capacity of this procedure to restore healthy microbiome, its tolerance and its potential efficacy on disease activity. If sucessfull, this trial would set the path to larger-scale clinical trials of FMT to treat axial SpA. Two-co primary objectives in a hierarchical design:

• to evaluate the capacity of FMT to correct dysbiosis in active axial SpA despite well-conducted phamacological treatment by replacing pre-existing dysbiotic microbiota with healthier microbiota.
• to explore the efficacy of FMT versus placebo on clinical evolution of SpA.

Conditions

Axial Spondyloarthritis

Keywords

Axial Spondyloarthritis; dysbiotic microbiota; Fecal microbiota transplantation; eubiotic microbiota

Outcome Measures

Primary Outcomes (2)

• Increase in gut Metagenome Species Pangenome (MSP) richness in the "intervention" arm.

  Fecal microbiota composition will be assessed by thorough microbial DNA sequencing (shotgun) at baseline (anytime between D-4 and D-1) and then at D28, D42, D84 and D168. The success will be evaluated by an increase in gut Metagenome Species Pangenome (MSP) richness over the period of study.

  at baseline and D 42

• The proportion of patients satisfying ASAS 20 improvement criteria by randomization group

  ASAS20 is defined by an improvement of ≥ 20% and of ≥ 10 points on a 0-100 numerical scale of 3 of the 4 following domains: global evaluation by the patient (PGA), pain, Bath Ankylosing Spondylitis Functional Index (BASFI) and inflammation (evaluated by the answer to both last questions of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) as well as an absence of deterioration from baseline by ≥ 20% and by ≥ 10 points in the fourth domain. The comparison of ASAS20 scores at D42 between randomization groups will be an exploratory analysis, considering literature data.

  at D 42

Secondary Outcomes (7)

• efficacy of FMT

  week 6

• Change of dysbiotic fecal microbiota

  at baseline, at weeks 3, 12 and 24

• Clinical improvement

  at baseline, weeks 3, 6, 12 and 24

• ESR and CRP levels

  at weeks 3, 6, 12 and 24

• CHANGE OF ASDAS_CRP and ASDAS_ESR

  at weeks 3, 6, 12 and 24

Study Arms (2)

Experimental

EXPERIMENTAL

active FMT

Drug: active FMT

Placebo

PLACEBO COMPARATOR

placebo

Drug: Placebo

Interventions

active FMT DRUG

MaaT033®, a lyophilized full-ecosystem intestinal microbiota delayed release oral capsule containing native, donor-derived (pooled from 4-6 donors) microbiome product manufactured by MaaT Pharma® will be delivered orally. Patients will receive 20 Maat033 capsules, each containing approximatively 0.42 g of microbiome product at once at day 0, then 3 capsules/day from day 1 through day 20.

Experimental

Placebo DRUG

Patients will receive 20 capsules placebo, each containing placebo at once at day 0, then 3 capsules/day from day 1 through day 20.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patient (age 18 to 75 years old) with SpA, meeting the ASAS classification criteria for axial SpA, with presence of radiographic sacro-illitis (ankylosing spondylitis) or not.
• Patient suffering of active SpA, with or without treatment, having a BASDAI score ≥ 4 (0-10) at baseline 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) for at least 4 months (or less in case of intolerance or contra-indication).
• Subjects are allowed to continue NSAID, sulfasalazin (≤ 3 g/day) and/or methotrextae ( ≤ 25 mg/week) and/or hydroxychloroquine (≤ 400 mg/day) and/or oral corticosteroid (≤ 10 mg/day of prednisone), as long as these treatments have remained at stable dose for 4 weeks prior to baseline.
• Subjects are allowed to continue anti-TNFα, anti-IL-17 or JAKinhibitor therapies, as long as these treatments have remained at stable dose for 3 months prior to baseline.
• Patient with health insurance (AME except).
• Patient is willing to provide written informed consent prior to enrolment and agrees to follow the protocol.

You may not qualify if:

• Patient under legal protection (guardianship or curatorship)
• 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
• Pregnant or breastfeeding woman
• Patient with IBD in active state, according to the judgment of the Investigator
• Active infection according to the judgment of the Investigator
• Patients with unstable severe condition other than axial SpA on that could jeopardize treatment procedure or evaluation according to the investigator's assessment
• Previous FMT treatment
• Contra-indication to colon preparation (Moviprep® or Moviprep orange®) according to SmPC
• Current or past evidence of bowel obstruction
• Confirmed or suspected intestinal ischemia
• Confirmed or suspected toxic megacolon or gastrointestinal perforation
• Extended colectomy (\> two-thirds of colon)
• Severe organ dysfunction
• Any contra-indication to swallow capsules
• Known allergy or intolerance to IMP and / or excipients according to Investigator's Brochure

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Fondation Arthritis & Clarins Worldwide 2016: collaborator

Study Sites (1)

Rheumatology Department, Ambroise Paré hospital - APHP

Boulogne-Billancourt, 92100, France

RECRUITING

MeSH Terms

Conditions

Axial Spondyloarthritis

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Study Officials

• Maxime Breban, MD, PhD

  Rheumatology Department - Ambroise Paré hospital - APHP

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maxime Breban, MD, PhD

CONTACT

+33 0149095674; maxime.breban@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2022
• First Posted: December 16, 2022
• Study Start: March 28, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 9, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)