Clinical trial NCT04944901: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Autistic Disorder
Keywords: Lactobacillus reuteri
autistic disorder
microbiome
Lead sponsor: Scioto Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2021-06-30
Enrollment: 15
Sex: ALL
Minimum age (years): 15
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Adverse Event of Special Interest (AESIs) and Adverse Events (AEs) Leading to Discontinuation
timeFrame: Approximately 98 days
measure: Sephadex Microspheres in the Stool
timeFrame: Period 1: Days 1 (pre-dose), 28 and 35; Period 2: Days 28 and 42 (period = 28 days and 14 days wash-out)
measure: Symptomatic Bacteremia With Positive L. Reuteri Identification
timeFrame: Approximately 98 days
Secondary outcomes:
measure: Mean Percent Change From Baseline in Biomarkers: Tumor Necrosis Factor-α
timeFrame: 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)
measure: Mean Percent Change From Baseline in Biomarkers: Serum High-sensitivity C-reactive Protein (Hs-CRP)
timeFrame: 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)
measure: Mean Percent Change From Baseline in Biomarkers: Stool Biomarkers, Fecal Calprotectin
timeFrame: Period 1: Days 1 (pre-dose), 28 and 35; Period 2: Days 28 and 35 (period = 28 days and 14 days wash-out)
measure: Mean Percent Change From Baseline in Biomarkers: Stool Biomarkers, Fecal Lactoferrin
timeFrame: Period 1: Days 1 (pre-dose), 28 and 35; Period 2: Days 28 and 35 (period = 28 days and 14 days wash-out)
measure: Mean Percent Change From Baseline in Biomarkers: Plasma Oxytocin
timeFrame: Day -28 to Day 0, Period 1: Day 28; Period 2: Days 1 and 28 (period = 28 days and 14 days wash-out)
measure: Mean Percent Change From Baseline in Biomarkers: Plasma Vasopressin
timeFrame: 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)
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Craig Erickson, MD
role: PRINCIPAL_INVESTIGATOR
References: