Fecal Microbiota Transplantation Trial in Axial Spondyloarthritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

7 Apr 2025 → ongoing

Decision date (initial)

2024-02-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Fondation Arthritis & Clarins Worldwide 2016 (private charity organization)

External identifiers

EU CT number

2023-504852-89-00

ClinicalTrials.gov

NCT05654753

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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.

Secondary objectives 11

1. Superior efficacy of FMT over placebo defined by an increase in MSP richness at D42 in the FMT group, superior to variation in the placebo group
2. Variation of MSP richness between baseline and D28, D84 and D168 in the FMT group
3. Comparison of MSP richness variation between baseline and D28, D84 and D168 between both arms
4. Clinical improvement over the 24 weeks following FMT or sham-FMT. We will compare between both arms the proportion of patients satisfying ASAS20 improvement criteria throughout this period as compared to baseline (D0)
5. Improvement according to "ASAS40" criteria at D28, D42, D84 and D168, which is defined in a manner similar to ASAS20 by an improvement of ≥ 40% and ≥ 20 points of 3 of the same 4 domains and an absence of deterioration of the 4th parameter by ≥20% and by ≥ 10 points
6. Achievement of a partial remission according to the ASAS definition at D28, D42, D84 and D168, which is defined as a value of < 20 points (on a scale of 0-100) in each of the 4 ASAS domains
7. Improvement of biological inflammation by CRP levels variation, at D28, D42, D84 and D168
8. Improvement of ASDAS_CRP at D28, D42, D84 and D168
9. Improvement of Bath Ankylosing Spondylitis Metrology Index (BASMI) at D28, D42, D84 and D168
10. Improvement of Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at D28, D42, D84 and D168
11. Decrease of non-steroidal anti-inflammatory drugs (NSAID) intake score at D28, D42, D84 and D168 as compared to baseline (D0)

Conditions and MedDRA coding

AXIAL SPONDYLOARTHRITIS

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 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
2. 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)
3. 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
4. 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
5. Women of childbearing potential with efficient contraceptive protection at the inclusion and during at least the interventional phase (D168)
6. Patient with health insurance (AME except)
7. Patient is willing to provide written informed consent prior to enrolment and agrees to follow the protocol

Exclusion criteria 23

1. Patient under legal protection (guardianship or curatorship)
2. 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
3. Pregnant or breastfeeding woman
4. Patient with IBD in active state, according to the judgment of the Investigator
5. Corticosteroid injection within 4 weeks before inclusion
6. Active infection according to the judgment of the Investigator
7. Any antibiotic (including Sulfasalazin) or antifungal treatment within 4 weeks before inclusion
8. Probiotics intake within 4 weeks before inclusion
9. Known infection with Clostridium difficile or Escherichia coli within 10 days before inclusion
10. Patients with unstable severe condition other than axial SpA on that could jeopardize treatment procedure or evaluation according to the investigator's assessment
11. Previous FMT treatment
12. Contra-indication to colon preparation (Moviprep® or Moviprep orange®) according to SmPC
13. Current or past evidence of bowel obstruction
14. Confirmed or suspected intestinal ischemia
15. Confirmed or suspected toxic megacolon or gastrointestinal perforation
16. Extended colectomy (> two-thirds of colon)
17. Any gastro-intestinal bleeding in the past 3 months before inclusion
18. Any history of gastro-intestinal surgery in the past 3 months before inclusion
19. Severe organ dysfunction
20. Any contra-indication to swallow capsules
21. Known allergy or intolerance to IMP and / or excipients according to Investigator’s Brochure
22. Lack of access to a refrigerator to store the medication (MaaT033® or MaaT030®)
23. Concomitant participation in another interventional clinical trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 11

1. 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
2. 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)
3. 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
4. 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
5. 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
6. 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
7. 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
8. 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
9. 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
10. 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
11. 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

Investigational products

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

Test 1

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Head of rheumatology department, Coordinating Investigator

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Head of rheumatology department, Coordinating Investigator

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Temporary halts 1 · Art. 38 CTR

Urgent safety measures 1 · Art. 54 CTR

Results and documents

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

Documents 10 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