28-Day Daily-dose Crossover Study of the Safety and Tolerability of SB-121 (Lactobacillus Reuteri With Sephadex® and Maltose) in Subjects, Ages 15 to 45 Years, Diagnosed With Autistic Disorder

Inclusion criteria

• Subject/parent (or authorized designee) has provided written informed consent for the study.
• Subject is ≥15 and ≤45 years of age at the time of enrollment.
• Diagnosis of autistic disorder (AD) as confirmed by the gold standard clinical interview using Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria and administration of the Autism Diagnostic Observation Schedule-2.
• Subject, if female and of childbearing potential, is not lactating or pregnant.
• Subject, if female, is either not of childbearing potential or is practicing an acceptable effective method of birth control.
• Subject is willing to comply with all study requirements (including the requirements for stool sampling and biobanking) and to return to the study facility for the follow-up evaluations, as required.

Exclusion criteria

• Subject has known allergy or significant adverse reaction to L reuteri, Sephadex®, maltose, or related compounds.
• Subject has previously had GI surgery, intestinal obstruction, Clostridium difficile infection or diverticulitis.
• Subject has travelled outside of the USA in the 30 days prior to screening.
• Subject has had a diarrheal illness in 30 days prior to screening.
• Subject currently has a fever or active/uncontrolled gastrointestinal (GI) symptoms (e.g., nausea, vomiting, diarrhea, constipation, abdominal distention, abdominal pain/cramps, flatulence) or has had these within 14 days prior to screening. If the GI symptoms are stable, in the opinion of the investigator, the subject can be enrolled.
• Subject has any immunological/autoimmune disorder including, but not limited to, systemic lupus erythematosis, rheumatoid arthritis, Sjögren's syndrome, inflammatory bowel disease, or immunoglobulin-deficiency disorder, that would increase the risk to the subject or interfere with the evaluation of SB-121.
• Subject has a documented history of human immunodeficiency virus (HIV), hepatitis B and/or hepatitis C
• Subject has implanted prosthetic devices including prosthetic heart valves.
• Subject has taken, or is taking, any of the following prohibited medications:

• A proton pump inhibitor within 2 weeks prior to screening
• Use of supplemental probiotics within 2 weeks prior to screening except for yogurt
• Current use of immunosuppressive medications, including corticosteroids
• Treatment with monoclonal antibodies within 4 weeks prior to screening
• Systemic antibiotics within 2 weeks prior to screening
• Subject has diabetes mellitus or is prediabetic.
• Subject has received any IP (or investigational device) within 30 days prior to screening.
• Subject has any of the following laboratory test results at Screening:

• An absolute neutrophil count of <1.5 × 10^9/L
• alanine aminotransferase or aspartate aminotransferase >1.5 × upper limit normal (ULN), total bilirubin >1.5 × ULN (subjects with known Gilbert's Syndrome can be included)
• serum creatinine >1.5 × ULN
• any other abnormal laboratory test that is clinically significant in the judgment of the investigator.
• Subject has an unstable medical condition or is otherwise considered unreliable or incapable, in the opinion of the investigator, of complying with the requirements of the protocol.
• Subject tests positive for drugs of abuse in a urine drug screen at screening.
• Subject has a history of alcohol abuse.