ALLOGENEIC FAECAL MICROBIOTA, POOLED for Gastrointestinal acute graft-versus-host disease (GI-aGvHD)

Inclusion criteria

• {"criterion_text":"- 1.\tAge ≥ 6 years and < 18 years old at the time point of informed consent.\n- 9. Signature of informed and written consent / assent by the participants legal representative.\n- 11. Use of an acceptable effective method of birth control for the course of the study for female of childbearing potential/sexually active male with partner of childbearing potential. This includes, but is not limited to: a) progestogen-only oral hormonal contraception b) male or female condom with or without spermicide c) cap, diaphragm or sponge with spermicide d) A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) are also considered acceptable birth control methods\n- 10. Negative urine or serum pregnancy test for females of childbearing potential within 72 hours prior to receiving the first dose of MaaT013 treatment.\n- 2.\tKarnofsky/Lansky performance status ≥ 40 at informed consent.\n- 3.\tWeight ≥ 15 kg.\n- 4.\tAllo-HSCT with any type of donor, stem cell source, GvHD prophylaxis or conditioning regimen.\n- 5.\tAcute GvHD episode with GI involvement per MAGIC guidelines (= grade II to IV), with or without involvement of other organs\n- 6.\tAdequate organ function, defined as: o Absolute neutrophil count (ANC) >500/µl, confirmed within 3 days prior to pre-treatment start. Use of growth factor supplementation to support the ANC count is allowed. o Platelet count > 10.000/µl, confirmed within 3 days prior to pre-treatment start. Use of platelet transfusion to support the platelet count is allowed.\n- 7.\tResistance to steroids and ruxolitinib. Resistance to steroids is defined as participants administered high-dose systemic CS (methylprednisolone 2 mg/kg/day – or equivalent prednisone dose 2.5 mg/kg/day), given alone or combined with CNI or mechanistic Target of Rapamycin (mTOR) inhibitor and either: o Lack of improvement (i.e., no decrease in stage in at least 1 involved organ system) after ≥ 5 days of treatment with CS at 2 mg/kg/d methylprednisolone equivalent dose, OR o Progression (i.e., increase of GvHD in any organ system or any new organ involvement) after ≥ 3 days of treatment with CS at 2 mg/kg/d methylprednisolone equivalent dose, OR o Participants treated with 1 mg/kg/d of CS as deemed intolerant by investigator to a dose of 2 mg/kg/d, and who correspond to the definition of SR participants, OR o Participants who previously began CS therapy at a lower dose (at least 1 mg/kg/d methylprednisolone equivalent) for skin or upper GI-GvHD but develop new GvHD in another organ system, OR o Participants intolerant to CS tapering, i.e., begin of CS at 2.0 mg/kg/d, demonstrate response, but show disease progression before a 50% decrease from the initial starting dose of CS is achieved. Resistance to ruxolitinib is defined as any of the following (adapted from (Mohty et al. 2020)): o Progression of GvHD compared to baseline after at least 5 days of treatment with ruxolitinib, based either on objective increase in stage/grade, or new organ involvement; or a lack of improvement for patients already at the highest stage or grade. OR o Lack of improvement in GvHD (PR or better) compared to baseline after at least 14 days of treatment with ruxolitinib, OR o Loss of response, defined as objective worsening of GvHD determined by increase in stage, grade or new organ involvement at any time after initial improvement, OR o Absence of CR or VGPR at D28 after ruxolitinib start. Intolerance to ruxolitinib is defined as: o GvHD manifestations that persist without improvement in participants who had grade 3 or higher ruxolitinib-emergent and ruxolitinib-attributed AE that did not resolve within 7 days of discontinuing ruxolitinib.\n- 8. Allo-HSCT participants with a non-malignant underlying disease may be enrolled only after their eligibility has been reviewed and approved by a multidisciplinary clinical board at clinical site."}

Exclusion criteria

• {"criterion_text":"- 1.\t Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring antimicrobials for management. Isolated urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.\n- 2.\tAny other diseases, metabolic dysfunction, physical examination findings, or clinical laboratory abnormalities giving reasonable suspicion of a disease or condition that in the opinion of the investigator would contraindicate study treatment.\n- 3.\tClinical presentation resembling de novo cGvHD or GvHD overlap syndrome with both acute and chronic GvHD features\n- 4. Known hypersensitivity to vancomycin or to any of the excipients listed in the corresponding SmPC.\n- 5.\tActive cytomegalovirus (CMV) colitis.\n- 6.\tRelapsed/persistent malignancy requiring rapid immune suppression withdrawal.\n- 7.\tPrevious lines of systemic aGvHD treatment other than CS and ruxolitinib.\n- 8.\tSevere organ dysfunction or other uncontrolled complication, unrelated to underlying GvHD, including: cholestatic disorders or unresolved veno-occlusive disease (VOD) of the liver (defined as persistent bilirubin abnormalities not attributable to GvHD and ongoing organ dysfunction, with the exception of Gilbert syndrome).\n- 9.\tClinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months before Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support that requires therapy.\n- 18. For France only: Children who are, or who are expected to become, adults under legal protection (tutelle, curatelle, or other court‑ordered protection), children whose parents are not affiliated with a French social security scheme and who therefore cannot be enrolled as dependents (‘ayants droit’), or children who would not be eligible for health coverage under the Protection Universelle Maladie (PUMA) upon reaching 18 years of age.\n- 10.\tClinically significant respiratory disease that requires mechanical ventilation support or oxygen support with a fraction of inspired oxygen at 50%.\n- 11.\tCurrent or past (<6 months) evidence of toxic megacolon, bowel obstruction or GI perforation\n- 12.\tAny condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.\n- 13.\tKnown allergy or intolerance to trehalose or maltodextrin.\n- 14.\tBreastfeeding females.\n- 15.\tParticipant having received any previous microbiome product (FMT). Note: Participants with medical history of probiotic intake are eligible.\n- 16.\tOther ongoing interventional protocol that might interfere with the current study’s primary and secondary endpoints.\n- 17.\tIn the investigator’s judgement, the participant is unlikely to complete all protocol-requiring trial visits or procedures, including FU visits, or comply with the trial requirements for participation."}

Primary endpoints

• {"endpoint_text":"- Co-primary: From inclusion to Month 6 (M6): Incidence of all AEs treatment-emergent AEs (TEAEs), serious AEs (SAEs), and assessment of all safety parameters (physical examinations, vital signs and laboratory clinically significant abnormalities).","definition_or_measurement_approach":"Incidence of AEs/TEAEs/SAEs and clinically significant abnormalities captured from inclusion through Month 6 by clinical assessments, vitals and laboratory tests."}
• {"endpoint_text":"- Co-Primary: From M6 to M12, incidence of SAEs and AESIs only.","definition_or_measurement_approach":"Incidence of SAEs and adverse events of special interest recorded between Month 6 and Month 12."}
• {"endpoint_text":"- Co-Primary: A comprehensive and detailed analysis of the nature, severity and frequency of AEs and SAEs will be performed.","definition_or_measurement_approach":"Descriptive analysis of AE nature, severity and frequency across the study period."}
• {"endpoint_text":"- Co-Primary: 1) Retention time ▪ Proportion of participants able to retain MaaT013 for at least 30 min. ▪ Proportion of participants able to retain MaaT013 for at least 1h. ▪ Proportion of participants able to retain MaaT013 for at least 2h.","definition_or_measurement_approach":"Proportion metrics of participants retaining administered MaaT013 for specified durations (30 minutes, 1 hour, 2 hours) following administration."}
• {"endpoint_text":"- Co-Primary: 2) Stress/anxiety evaluated with the depression anxiety stress scale","definition_or_measurement_approach":"Stress/anxiety measured using the Depression Anxiety Stress Scale at specified timepoints."}
• {"endpoint_text":"- Co-Primary: 3) Procedure-related AEs ▪ Solicited TEAEs related to administration procedure will be collected within 72h after each MaaT013 administration","definition_or_measurement_approach":"Solicited treatment-emergent AEs related to the administration procedure collected within 72 hours after each administration."}
• {"endpoint_text":"- Co-Primary: 4) Factors compromising the administration of the study drug ▪ TEAEs leading to treatment discontinuation, interruption and postponement will be collected.","definition_or_measurement_approach":"Collection and summarisation of TEAEs that lead to discontinuation, interruption or postponement of MaaT013 administration."}

Secondary endpoints

• {"endpoint_text":"- Proportion of participants achieving complete response (CR), very good partial response (VGPR) or partial response (PR) for GI at D28, D56, M3, M6 and M12 assessed by IRC and investigator, without requirement for additional systemic therapies prior to the assessment time point.","definition_or_measurement_approach":"Response rates (CR/VGPR/PR) at D28, D56, M3, M6 and M12 assessed by independent review committee and investigator, excluding participants who received additional systemic therapies prior to assessment."}
• {"endpoint_text":"- Proportion of participants achieving CR, VGPR or PR for all organs at D28, D56, M3, M6 and M12 assessed by IRC and investigator, without requirement for additional systemic therapies prior to the assessment time point.","definition_or_measurement_approach":"Overall organ response rates at specified timepoints assessed by IRC and investigator without prior additional systemic therapy."}
• {"endpoint_text":"- DOR is assessed for responders only and is defined as the time from first response (at least PR) until aGvHD progression (loss of at least PR compared to baseline, confirmed with 2 evaluations), or the starting date of additional systemic therapies for aGvHD. Onset of cGvHD, or death without prior observation of aGvHD progression are considered as competing risks. DOR will be evaluated for both GI and overall aGvHD, until M12.","definition_or_measurement_approach":"Duration of response measured from first response (≥PR) to progression or start of additional systemic therapy; competing risks handled as specified; evaluated to M12."}
• {"endpoint_text":"- OS is defined as the time from the date of first MaaT013 administration to the date of death due to any cause.","definition_or_measurement_approach":"Overall survival measured from first administration to death from any cause."}
• {"endpoint_text":"- PFS is defined as the time from first MaaT013 administration to the date of underlying malignancy relapse, progression or death (all causes). PFS will be evaluated up to M12.","definition_or_measurement_approach":"Progression-free survival from first administration to relapse/progression of underlying malignancy or death; evaluated to M12."}
• {"endpoint_text":"- TTP is defined as the time from first MaaT013 administration to the date of underlying malignancy relapse or progression. TTP will be evaluated up to M12.","definition_or_measurement_approach":"Time to progression from first administration to relapse/progression of underlying malignancy; evaluated to M12."}
• {"endpoint_text":"- SFR is defined as the number and percentage of participants who are steroid-free, defined by a daily dose of CS ≤ 0.25 mg/kg/day (methylprednisolone equivalent dose). Steroid-free rate at D28, D56, M3, M6, and M12 will be provided. SFR will be evaluated up to M12.","definition_or_measurement_approach":"Steroid-free rate defined as CS daily dose ≤0.25 mg/kg/day; reported at specified timepoints up to M12."}
• {"endpoint_text":"- Cumulative total dose of CS in mg/kg from date of first MaaT013 administration to D28, D56, M3, M6, and M12 will be derived and summarized.","definition_or_measurement_approach":"Cumulative corticosteroid dose (mg/kg) calculated from first administration to each timepoint and summarized."}
• {"endpoint_text":"- Number and percentage of participants who definitively tapered off CS at M12.","definition_or_measurement_approach":"Count and percentage of participants who have definitively discontinued corticosteroids by Month 12."}
• {"endpoint_text":"- Proportion of participants with cGvHD, defined as the diagnosis of any cGvHD, including mild, moderate or severe, up to M12 (NIH criteria).","definition_or_measurement_approach":"Proportion diagnosed with chronic GvHD up to M12 per NIH criteria."}

Methods

• Recruitment arrangements documents are provided for France (K1_FR_Recruitment arrangments_For publication).
• Recruitment arrangements documents are provided for Italy (K1_IT_Recruitment and Informed consent procedure).
• Recruitment arrangements documents are provided for Spain (K1_ES_Recruitment arrangments).
• Recruitment arrangements documents are provided for Netherlands (K1_NL_Recruitment arrangement).
• Recruitment website lay summary for Prinses Maxima Center (Netherlands) (K2_NL_Recruitment website lay summary_Prinses Maxima Center).

France

Earliest CTIS Part Ii Submission Date

03-04-2026

Latest Decision Or Authorization Date

17-04-2026

Processing Time Days

14

Number Of Sites

4

Number Of Participants

6

Italy

Earliest CTIS Part Ii Submission Date

24-03-2026

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

29

Number Of Sites

4

Number Of Participants

3

Spain

Earliest CTIS Part Ii Submission Date

10-04-2026

Latest Decision Or Authorization Date

21-04-2026

Processing Time Days

11

Number Of Sites

3

Number Of Participants

6

Netherlands

Earliest CTIS Part Ii Submission Date

24-03-2026

Latest Decision Or Authorization Date

21-04-2026

Processing Time Days

28

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

MaaT PHARMA

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Allucent (NL) B.V.

Responsibilities

CRO Services

Name

Soladis Clinical Studies

Responsibilities

CRO Services

Third parties

• {"country":"Germany","full_name":"Eurofins Genomics Europe Food/Environment/White Biotech Products & Services","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Mt-G Medical Translation GmbH & Co. KG","duties_or_roles":"Translation services","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Labfish Rental Solutions GmbH","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Allucent (NL) B.V.","duties_or_roles":"CRO Services","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Soladis Clinical Studies","duties_or_roles":"CRO Services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient concierge services","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"France","full_name":"Biofortis","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}