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

Randomized, Double-blind, Placebo-controlled, 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

SB-121 is being developed for use in the treatment of autistic disorder (AD).

This study is a multiple-dose, randomized, double-blind, placebo-controlled, cross-over single-site Phase I study.

The primary objective is to evaluate the safety and tolerability of multiple doses of SB-121 in subjects ages 15 to 45 years with AD.

Additionally, multiple measures of AD, as well as mechanistic biomarkers, will be assessed in order to inform later stage trials.

Study Overview

• Status: Completed
• Conditions: Autistic Disorder
• Intervention / Treatment: Drug: SB-121; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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:

  1. A proton pump inhibitor within 2 weeks prior to screening
  2. Use of supplemental probiotics within 2 weeks prior to screening except for yogurt
  3. Current use of immunosuppressive medications, including corticosteroids
  4. Treatment with monoclonal antibodies within 4 weeks prior to screening
  5. 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:

  1. An absolute neutrophil count of <1.5 × 10^9/L
  2. 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)
  3. serum creatinine >1.5 × ULN
  4. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SB-121; One dose of SB-121 daily for 28 days according to the treatment group to which they are allocated. Administration: Oral	Drug: SB-121; SB-121 is a formulation of L. reuteri
Placebo Comparator: Placebo; One dose of placebo daily for 28 days according to the treatment group to which they are allocated. Administration: Oral	Drug: Placebo; Placebo oral formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event of Special Interest (AESIs) and Adverse Events (AEs) Leading to Discontinuation	Adverse event of special interest (AESIs) and adverse events (AEs) leading to discontinuation from the study are presented. Treatment Period 1: 2 participants reported 4 events in the SB-121 group and 3 participant reported 6 events in the placebo group. Treatment Period 2: 1 participant reported 3 events in the SB-121 group and 1 participant reported 4 events in the placebo group.	Approximately 98 days
Sephadex Microspheres in the Stool	The presence of Sephadex microspheres in the stool was assessed. The number of participants with data available at each stage are presented.	Period 1: Days 1 (pre-dose), 28 and 35; Period 2: Days 28 and 42 (period = 28 days and 14 days wash-out)
Symptomatic Bacteremia With Positive L. Reuteri Identification	The presence of symptomatic bacteremia with positive L. reuteri identification was assessed and none of the participants in either group showed any clinical features of suspected bacteremia in this study.	Approximately 98 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Percent Change From Baseline in Biomarkers: Tumor Necrosis Factor-α	Mean (standard deviation) percent changes from baseline in tumor necrosis factor-α	Day -28 to Day 0, Period 1: Day 28; Period 2: Days 1 (pre-dose) and 28 (period = 28 days and 14 days wash-out)
Mean Percent Change From Baseline in Biomarkers: Serum High-sensitivity C-reactive Protein (Hs-CRP)	Mean (standard deviation) percent change from baseline in serum high-sensitivity C-reactive protein (hs-CRP)	Day -28 to Day 0, Period 1: Day 28; Period 2: Days 1 (pre-dose) and 28 (period = 28 days and 14 days wash-out)
Mean Percent Change From Baseline in Biomarkers: Stool Biomarkers, Fecal Calprotectin	Mean (standard deviation) percent change from baseline in stool biomarkers, fecal calprotectin. The number of participants with data available are presented.	Period 1: Days 1 (pre-dose), 28 and 35; Period 2: Days 28 and 35 (period = 28 days and 14 days wash-out)
Mean Percent Change From Baseline in Biomarkers: Stool Biomarkers, Fecal Lactoferrin	Mean (standard deviation) percent change from baseline in stool biomarkers, fecal lactoferrin. The number of participants with data available are presented.	Period 1: Days 1 (pre-dose), 28 and 35; Period 2: Days 28 and 35 (period = 28 days and 14 days wash-out)
Mean Percent Change From Baseline in Biomarkers: Plasma Oxytocin	The mean (standard deviation) percent changes from baseline in plasma oxytocin.	Day -28 to Day 0, Period 1: Day 28; Period 2: Days 1 and 28 (period = 28 days and 14 days wash-out)
Mean Percent Change From Baseline in Biomarkers: Plasma Vasopressin	Mean (standard deviation) percent changes from baseline in plasma vasopressin levels	Day -28 to Day 0, Period 1: Day 28; Period 2: Days 1 (pre-dose) and 28 (period = 28 days and 14 days wash-out)

Collaborators and Investigators

• Sponsor: Scioto Biosciences, Inc.
• Investigators: Principal Investigator: Craig Erickson, MD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2021
• Primary Completion (Actual): March 3, 2022
• Study Completion (Actual): March 3, 2022

Study Registration Dates

• First Submitted: June 21, 2021
• First Submitted That Met QC Criteria: June 28, 2021
• First Posted (Actual): June 30, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: microbiome; autistic disorder; Lactobacillus reuteri
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder
• Other Study ID Numbers: SBI-SB121-20-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No