TSO in Pediatric Autistic Spectrum Disorders

Study Overview
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Brief Summary
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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)

Detailed Description
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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: Placebo (n= 20 patients). These patients will receive a blinded dose of placebo every other week. 2500 TSO every other week (n= 20 patients). These patients will receive a blinded dose of TSO every other week 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.

Official Title
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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

Conditions
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Autistic Spectrum Disorders

Intervention / Treatment
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* Drug: TSO
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, ages 6 to 17 years, inclusive Diagnosis via Diagnostic and Statistical Manual for Mental Disorders- Forth Edition (DSM-IV)-and confirmed by Autism Diagnostic Observation Schedule (ADOSI): CGI-Severity score > 4 and ABC irritability score > 18 Mental age of > 18 months Weight of at least ** kg Currently psychotropic medication free or on stable dose of psychotropic medication for at least 3 months prior to the study. Willing to comply with the schedule of study visits and protocol requirements Patient and/or guardian have the ability to provide informed consent Exclusion Criteria: Previous diagnosis of Rett's Disorder, Aspergers Disorder, Childhood Disintegrative Disorder, Fragile X Syndrome, or other disorders on the autism spectrum History of Bipolar Disorder, Psychotic Disorders, or major Depression Seizure within the previous 6 months 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 Patient with history of drug or alcohol abuse within 6 months prior to Screening Patient with evidence of poor compliance with medical advice and instruction including diet or medication Patient is unable or unwilling to swallow study medication suspension 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 Patient who has participated in another clinical trial within 30 days of Screening for this trial and/or any experimental treatment for this population Females of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period Females who are pregnant or breastfeeding at the time of enrollment Patients with any of the following laboratory values: White blood cell count ≤ 3,000/mm3 (≤ 3.0 x 109/L) or ≥ 14,000/mm3 (≥14 x 109/L) Platelet count ≤ 100,000/μL (≤100 x 109/L) Serum creatinine ≥ 1.5 mg/dL (≥ 132.6 μmol/L) or >2 x upper limit of normal (ULN) AST (SGOT) or ALT (SGPT) > 2 x ULN Total bilirubin >2 mg/dL (34 μmol/L) Hemoglobin < 9 g/dL

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: TSO 2500<br>2500 TSO every other week | Drug: TSO<br>* 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<br>* Other names: or matching placebo administered orally at the investigational center;|
| Active Comparator: 7500 TSO<br>7500 TSO every other week | Drug: TSO<br>* 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<br>* Other names: or matching placebo administered orally at the investigational center;|
| Placebo Comparator: Placebo<br>placebo every other week. | Drug: Placebo<br> <br> |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism, Trichuris Suis Ova, Behavior, Irritability