Phase IIa Open-Label Study on the Efficacy and Safety of Allogeneic Fecal Microbiota Transplantation in Pediatric Autism Spectrum Disorder with Gastrointestinal Symptoms

The primary objective of this study is to **assess the initial efficacy** of fecal microbiota transplantation (FMT) on gastrointestinal symptoms in children aged 36 to 72 months with autism spectrum disorders (ASD) at week 18. This is clinically relevant as gastrointestinal symptoms are prevalent in children with ASD and can significantly impact their quality of life and overall health. Addressing these symptoms may lead to improvements in both gastrointestinal and behavioral outcomes.

Secondary objectives include:

• Estimating changes in autistic core symptoms, which could provide insights into the broader impact of FMT on ASD.
• Estimating the safety of FMT by monitoring the occurrence of side effects, ensuring the intervention's risk profile is acceptable.
• Estimating the tolerability of FMT, which is crucial for determining the feasibility of this treatment in pediatric populations.
• Estimating the impact of FMT on the quality of life of both children and their parents, as improvements could enhance daily functioning and family dynamics.
• Measuring the impact on gut microbiota diversity and immune markers, which may elucidate the biological mechanisms underlying the effects of FMT.

The clinical trial involves a study population of children aged **36 to 72 months** diagnosed with **autism spectrum disorder** (ASD). The trial includes both male and female participants, and the population is considered vulnerable due to the young age of the subjects. The sponsor has not provided the total number of participants. Participants were selected based on specific criteria, including a confirmed ASD diagnosis according to DSM-5 criteria and the presence of gastrointestinal symptoms, such as diarrhea, abdominal pain, constipation, indigestion, or reflux, persisting for over a year. Consent from all legal guardians and social insurance affiliation were also required. The trial aims to assess the initial efficacy of fecal microbiota transplantation on gastrointestinal symptoms in this demographic at week 18. Lifestyle considerations such as diet, physical activity, or habits were not specified by the sponsor.

The clinical trial is designed as an open-label, phase IIa study to evaluate the effect and safety of **fecal microbiota transplantation** (FMT) in children diagnosed with **autism spectrum disorder** (ASD) and concurrent gastrointestinal symptoms. The trial aims to assess the initial efficacy of FMT on gastrointestinal symptoms over an 18-week period. The study will involve children aged 36 to 72 months who meet specific inclusion criteria, including a confirmed ASD diagnosis based on DSM-5 criteria, persistent gastrointestinal symptoms, and consent from legal guardians. The trial will utilize an **enema** formulation of pooled allogeneic fecal microbiota, administered rectally.

The trial is expected to commence recruitment on August 1, 2025, and conclude by January 31, 2027. Participants will be involved in the study for a maximum of 12 months, with the primary endpoint being the reduction of more than 50% in the composite score of the Gastrointestinal Symptoms Rating Scale (GSRS) by week 18. Secondary endpoints include improvements in autistic core symptoms, global improvement, and monitoring of FMT side effects. The study will also evaluate adherence to the FMT process and quality of life using various scales and questionnaires.

Study visits are structured as follows: an initial inclusion (screening) visit to confirm eligibility, followed by treatment administration and monitoring visits at day 0, day 5, week 4, week 18, week 24, and month 12. The end-of-study visit will occur at month 12. Participants may be withdrawn from the study if they experience significant adverse events, fail to adhere to study protocols, or withdraw consent. The trial is not categorized as low intervention and is conducted under the auspices of Assistance Publique - Hôpitaux de Paris.

The clinical trial involves the administration of an **experimental medication** known as "Enema transplant of fecal microbiota 25g/100mL." This medication is formulated as an **enema** and is intended for **rectal use**. The active substance in this treatment is **allogeneic fecal microbiota, pooled**, which is classified as a structurally diverse substance used in cell therapy. The enema is administered with a maximum daily dose of 25 grams, and the total dose should not exceed 75 grams over the course of the treatment. The maximum treatment period is 14 days. The enema is produced by Assistance Publique - Hôpitaux de Paris and is not a pediatric formulation.

In this study, there are no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments mentioned. The focus is solely on evaluating the efficacy and safety of the fecal microbiota transplantation in children with autism spectrum disorders and gastrointestinal symptoms. Compliance with the dosing schedule and administration route is crucial for the integrity of the trial results. Participants' adherence to the treatment regimen will be monitored throughout the study to ensure accurate assessment of the treatment's effects.

The clinical trial aims to assess the efficacy of fecal microbiota transplantation in children with autism spectrum disorders and gastrointestinal symptoms. The primary endpoint for evaluating efficacy is the rate of children achieving a success, defined as a reduction of more than 50% in the composite score of the Gastrointestinal Symptoms Rating Scale (GSRS). This scale, validated in French, measures the intensity of five gastrointestinal symptoms: diarrhea, abdominal pain, constipation, indigestion, and reflux. The GSRS will be evaluated by parents from the time of inclusion to week 18.

Secondary endpoints include improvements in autistic core symptoms and global improvement, assessed at multiple timepoints: week 0, week 4, week 18, week 24, and month 12. These will be measured using various questionnaires and scales. Additionally, the Pediatric Adverse Event Rating Scale will be used to monitor side effects of the fecal microbiota transplantation at day 0, day 5, week 4, week 18, week 24, and month 12. Adherence to the fecal microbiota transplantation process, dropout rates, and reasons for dropout will also be evaluated. Stool consistency will be assessed using the Bristol Stool Form Scale by parents from week 0 to week 4 and from week 17 to week 18. The Caregiver Strain Index will be used to measure global improvement, assessed by a psychologist at week 0, week 4, week 18, week 24, and month 12. The Pediatric Quality of Life Inventory (PedsQL) will be evaluated at week 0, week 18, and month 12.