Safety, Tolerability, and Feasibility of Rectal MaaT013 (Allogeneic Pooled Fecal Microbiota) in Ruxolitinib‑Refractory Pediatric and Adolescent Gastrointestinal Acute Graft‑Versus‑Host Disease

The co‑primary objective is to evaluate the safety and tolerability of MaaT013 and to determine the feasibility of its rectal administration in paediatric and adolescent participants with refractory or intolerant Gastrointestinal acute graft-versus-host disease. Establishing a safety profile is essential for informing subsequent therapeutic development in this high‑risk population.

Secondary objectives include:

• Assessment of overall response rate for GI‑aGvHD at days 28, 56, month 3, month 6 and month 12 by independent review committee and investigator.
• Assessment of overall response rate for all affected organs at the same time points.
• Evaluation of duration of response.
• Determination of overall survival.
• Determination of progression‑free survival and time to progression.
• Measurement of the steroid‑free rate and cumulative corticosteroid exposure.
• Frequency of participants successfully tapering off corticosteroids.
• Incidence of chronic graft‑versus‑host disease.

The trial enrolled pediatric participants aged 6 to < 18 years, encompassing both female and male subjects. Eligibility required a performance status (Karnofsky/Lansky) of ≥ 40, a body weight of at least 15 kg, and adequate hematologic and platelet parameters. All enrollees had undergone allogeneic hematopoietic stem‑cell transplantation and experienced an episode of Gastrointestinal Acute Graft-versus-Host Disease (GI-aGvHD) of grade II to IV, with or without additional organ involvement. Inclusion mandated resistance to both high‑dose corticosteroids and ruxolitinib, as defined by lack of improvement or disease progression under specified treatment durations. Participants of child‑bearing potential were required to use effective contraception and provide a negative pregnancy test within 72 hours prior to dosing. The sponsor did not provide the total number of participants. Selection was based on the outlined clinical criteria and review by a multidisciplinary clinical board for subjects with non‑malignant underlying conditions.

The study is a multicentre, phase II, open‑label, single‑arm trial evaluating the safety, tolerability, feasibility and efficacy of the investigational rectal suspension MaaT013 in paediatric and adolescent participants (aged ≥ 6 to < 18 years) with Gastrointestinal Acute Graft-versus-Host Disease refractory or intolerant to ruxolitinib and steroids. Participants undergo an initial screening visit to confirm eligibility criteria, followed by a baseline visit on the day of the first MaaT013 administration. Subsequent follow‑up visits are scheduled at Day 28, Day 56, Month 3, Month 6 and Month 12, with the final end‑of‑study visit occurring at Month 12. At each visit, safety assessments (adverse‑event monitoring, physical examination, vital signs, laboratory tests), procedural tolerance (retention time of the study product), and efficacy evaluations (organ‑specific response, steroid‑free status, overall survival, progression‑free survival) are performed. Participants remain in the study for a maximum of 12 months from the first dose; early termination may occur if serious adverse events, intolerable procedural complications, inability to retain the investigational product for the required duration, or withdrawal of consent arise. The overall trial duration, including recruitment, spans from May 2026 to August 2029.

The investigational product MaaT013 is a pooled allogeneic faecal microbiota suspension supplied as a rectal solution. Each dose consists of 150 ml of the suspension, administered via the rectal route. The pharmaceutical form is identified as “RECTAL SOLUTION.” Dosing frequency and schedule are defined by the study protocol, and participants receive the assigned dose under direct observation to ensure adherence.

Standard‑of‑care therapy includes oral vancomycin, supplied in the pharmaceutical form “PHF00230MIG.” The prescribed dose is 500 mg administered orally. The background medication is provided in accordance with routine clinical practice for gastrointestinal acute graft‑versus‑host disease. Administration of both the investigational and background treatments is recorded in the study case report form, and compliance is monitored through dose administration logs and periodic verification by study staff.

Efficacy will be evaluated using several quantitative and categorical endpoints. The primary efficacy parameters are the proportions of participants achieving a complete response, very good partial response, or partial response for gastrointestinal acute graft-versus-host disease (GI‑aGvHD) and for overall organ involvement. These responses are assessed at day 28, day 56, month 3, month 6, and month 12 by both an independent review committee and the investigator, without the need for additional systemic therapy prior to the assessment time point. Additional efficacy measures include duration of response (time from first documented response ≥ partial response to disease progression or initiation of new systemic therapy), overall survival (time from first MaaT013 administration to death from any cause), progression‑free survival (time from first administration to malignancy relapse, progression, or death), and time to progression (time from first administration to malignancy relapse or progression). Steroid‑free rate (percentage of participants with corticosteroid dose ≤ 0.25 mg/kg/day) and cumulative corticosteroid dose (mg/kg) are recorded at the same scheduled visits, along with the proportion of participants who have definitively tapered off corticosteroids by month 12. Incidence of chronic graft‑versus‑host disease is documented up to month 12 using NIH criteria.

Response assessments are performed using standardized aGvHD grading criteria applied by the IRC and investigators. Corticosteroid dosing is calculated as methylprednisolone‑equivalent daily dose to determine steroid‑free status. Survival and disease‑progression endpoints are derived from patient records and are analyzed using time‑to‑event statistical methods, with competing risks (e.g., onset of chronic GVHD or death) accounted for in the duration of response analysis. All efficacy data are collected at the predefined time points (D28, D56, M3, M6, M12) and summarized descriptively and inferentially according to the trial statistical analysis plan.