TSO in Pediatric Autistic Spectrum Disorders (TSO)

A Phase 2 Randomized Three-Arm Double-Blind Placebo-Controlled Study to Evaluate the Safety and Efficacy of 16 Weeks of Treatment With Trichuris Suis Ova (TSO) Therapy in Pediatric Patients Ages 6 to 17 With Autism

The primary objective of this study is to evaluate and compare the safety and efficacy of Trichuris suis ova (TSO) therapy (versus placebo) in pediatric patients with autism.

Evaluation of the safety and tolerability of treatment with TSO in the target population across the dose range being tested is considered a primary objective, while the primary efficacy objective will be assessed via the change from baseline in the Aberrant Behavior Checklist (ABC) subscale scores.

Dose response will be considered a primary objective as well.

Secondary assessments of efficacy will be assessed via:

• The change from baseline in the Clinical Global Impression scale (CGI-I)

Study Overview

• Status: Terminated
• Conditions: Autistic Spectrum Disorders
• Intervention / Treatment: Drug: Placebo; Drug: TSO

Detailed Description

This is a randomized, three-arm double-blind, placebo-controlled, single-center study to evaluate the effects of oral administration of Trichuris suis ova (as compared to placebo) in the treatment of pediatric patients diagnosed with Autism. The target sample size to be randomized into the study will be approximately 60, randomly assigned in a 1:1:1 ratio to one of three treatment groups:

1. Placebo (n= 20 patients). These patients will receive a blinded dose of placebo every other week.
2. 2500 TSO every other week (n= 20 patients). These patients will receive a blinded dose of TSO every other week
3. 7500 TSO every other week (n= 20 patients). These patients will receive a blinded dose of TSO every other week

Double-blind treatment will be given for a total of 16 weeks.

This study will have 3 phases:

• Screening period, comprising up to 5 weeks prior to Baseline (Day 1)
• Double-blind treatment period for 16 weeks
• An untreated follow-up period for 26 weeks. Following informed consent, patients will be screened on the basis of diagnosis of autism, vital signs, clinical laboratories medical history and a physical examination. Eligible patients will be randomized to double-blind treatment with TSO 2500 every other week, TSO 7500 every other week, or placebo every other week, in a ratio of 1:1:1. During the double-blind study phase, study drug will be provided in the clinic in a liquid form and will be administered every other week, starting with the Baseline visit, through Week 14. Week 14 is the last double-blind treatment administration of the study, while Week 16 is the primary time point for assessment of efficacy. Patients will return to the clinic every other week during the double blind treatment period.

After completion of the double-blind phase, patients will then return to the clinic 26 weeks following the last dose of study medication for a safety assessment and stool sample culture.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Mount Scopus
    • Jerusalem, Mount Scopus, Israel, 91240
      • The Neuro-Cognitive Center, Pediatric Division, Hadassah-Hebrew University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females, ages 6 to 17 years, inclusive

2. Diagnosis via Diagnostic and Statistical Manual for Mental Disorders- Forth Edition (DSM-IV)-and confirmed by Autism Diagnostic Observation

   Schedule (ADOSI):

3. CGI-Severity score > 4 and ABC irritability score > 18
4. Mental age of > 18 months
5. Weight of at least ** kg
6. Currently psychotropic medication free or on stable dose of psychotropic medication for at least 3 months prior to the study.
7. Willing to comply with the schedule of study visits and protocol requirements
8. Patient and/or guardian have the ability to provide informed consent

Exclusion Criteria:

1. Previous diagnosis of Rett's Disorder, Aspergers Disorder, Childhood Disintegrative Disorder, Fragile X Syndrome, or other disorders on the autism spectrum
2. History of Bipolar Disorder, Psychotic Disorders, or major Depression
3. Seizure within the previous 6 months
4. Patient received antibiotic, antifungal or antiparasitic medication in the last 2 weeks prior to Screening and/or would potentially require this during the study treatment period
5. Patient with history of drug or alcohol abuse within 6 months prior to Screening
6. Patient with evidence of poor compliance with medical advice and instruction including diet or medication
7. Patient is unable or unwilling to swallow study medication suspension
8. Patient with a significant medical condition which puts the patient at risk for study participation and/or for any reason is considered by the Investigator to be an unsuitable candidate to receive TSO or is potentially put at risk by study procedures
9. Patient who has participated in another clinical trial within 30 days of Screening for this trial and/or any experimental treatment for this population
10. Females of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period
11. Females who are pregnant or breastfeeding at the time of enrollment

12. Patients with any of the following laboratory values:

    1. White blood cell count ≤ 3,000/mm3 (≤ 3.0 x 109/L) or ≥ 14,000/mm3 (≥14 x 109/L)
    2. Platelet count ≤ 100,000/μL (≤100 x 109/L)
    3. Serum creatinine ≥ 1.5 mg/dL (≥ 132.6 μmol/L) or >2 x upper limit of normal (ULN)
    4. AST (SGOT) or ALT (SGPT) > 2 x ULN
    5. Total bilirubin >2 mg/dL (34 μmol/L)
    6. Hemoglobin < 9 g/dL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TSO 2500; 2500 TSO every other week	Drug: TSO; There is evidence of a relationship between ASD symptomatology and immune dysfunction suggests that immunomodulatory treatments effective in other autoimmune disorders might be investigated in ASD, including Trichuris Ova Suis (TSO), a helminth porcine whipworm; Other Names: Each dose of 2500 and 7500 active Trichuris suis ova will be provided; in 15 mL of aqueous suspension (supplied in 30 mL glass container); or matching placebo administered orally at the investigational center
Active Comparator: 7500 TSO; 7500 TSO every other week	Drug: TSO; There is evidence of a relationship between ASD symptomatology and immune dysfunction suggests that immunomodulatory treatments effective in other autoimmune disorders might be investigated in ASD, including Trichuris Ova Suis (TSO), a helminth porcine whipworm; Other Names: Each dose of 2500 and 7500 active Trichuris suis ova will be provided; in 15 mL of aqueous suspension (supplied in 30 mL glass container); or matching placebo administered orally at the investigational center
Placebo Comparator: Placebo; placebo every other week.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aberrant Behavior Checklist (ABC) subscale scores	The ABC consists of 58 questions and the five subscales as described above. Each question on the ABC is rated on a 4-point scale: 0 = 'not a problem,' 1 ='the behavior is a problem but slight in degree,' 2 = 'the problem is moderately serious,' and 3 = 'the problem is severe in degree.' The subscale score is the sum of the responses to the questions that make up the subscale.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary assessments of efficacy will be assessed via: The change from baseline in the CY-BOCS, CGI-I, SRS, SCQ.	Secondary assessments of efficacy will be assessed via: • The change from baseline in the Clinical Global Impression - Improvement scale (CGI-I)	49 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Laboratory	Clinical laboratories will include hematology and serum chemistry panels, as well as C-reactive protein	49 weeks

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization

Publications and helpful links

General Publications

• Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV. Trichuris suis therapy in Crohn's disease. Gut. 2005 Jan;54(1):87-90. doi: 10.1136/gut.2004.041749.
• Fleming JO, Isaak A, Lee JE, Luzzio CC, Carrithers MD, Cook TD, Field AS, Boland J, Fabry Z. Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study. Mult Scler. 2011 Jun;17(6):743-54. doi: 10.1177/1352458511398054. Epub 2011 Mar 3.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: November 19, 2012
• First Submitted That Met QC Criteria: November 22, 2012
• First Posted (Estimate): November 28, 2012

Study Record Updates

• Last Update Posted (Estimate): February 2, 2016
• Last Update Submitted That Met QC Criteria: January 31, 2016
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Behavior; Trichuris Suis Ova; Autism; Irritability
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
• Other Study ID Numbers: 0522-12-HMO