<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01734941</url>
  </required_header>
  <id_info>
    <org_study_id>0522-12-HMO</org_study_id>
    <nct_id>NCT01734941</nct_id>
  </id_info>
  <brief_title>TSO in Pediatric Autistic Spectrum Disorders</brief_title>
  <acronym>TSO</acronym>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hadassah Medical Organization</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hadassah Medical Organization</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to evaluate and compare the safety and efficacy of&#xD;
      Trichuris suis ova (TSO) therapy (versus placebo) in pediatric patients with autism.&#xD;
&#xD;
      Evaluation of the safety and tolerability of treatment with TSO in the target population&#xD;
      across the dose range being tested is considered a primary objective, while the primary&#xD;
      efficacy objective will be assessed via the change from baseline in the Aberrant Behavior&#xD;
      Checklist (ABC) subscale scores.&#xD;
&#xD;
      Dose response will be considered a primary objective as well.&#xD;
&#xD;
      Secondary assessments of efficacy will be assessed via:&#xD;
&#xD;
      • The change from baseline in the Clinical Global Impression scale (CGI-I)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, three-arm double-blind, placebo-controlled, single-center study to&#xD;
      evaluate the effects of oral administration of Trichuris suis ova (as compared to placebo) in&#xD;
      the treatment of pediatric patients diagnosed with Autism. The target sample size to be&#xD;
      randomized into the study will be approximately 60, randomly assigned in a 1:1:1 ratio to one&#xD;
      of three treatment groups:&#xD;
&#xD;
        1. Placebo (n= 20 patients). These patients will receive a blinded dose of placebo every&#xD;
           other week.&#xD;
&#xD;
        2. 2500 TSO every other week (n= 20 patients). These patients will receive a blinded dose&#xD;
           of TSO every other week&#xD;
&#xD;
        3. 7500 TSO every other week (n= 20 patients). These patients will receive a blinded dose&#xD;
           of TSO every other week&#xD;
&#xD;
      Double-blind treatment will be given for a total of 16 weeks.&#xD;
&#xD;
      This study will have 3 phases:&#xD;
&#xD;
        -  Screening period, comprising up to 5 weeks prior to Baseline (Day 1)&#xD;
&#xD;
        -  Double-blind treatment period for 16 weeks&#xD;
&#xD;
        -  An untreated follow-up period for 26 weeks. Following informed consent, patients will be&#xD;
           screened on the basis of diagnosis of autism, vital signs, clinical laboratories medical&#xD;
           history and a physical examination. Eligible patients will be randomized to double-blind&#xD;
           treatment with TSO 2500 every other week, TSO 7500 every other week, or placebo every&#xD;
           other week, in a ratio of 1:1:1. During the double-blind study phase, study drug will be&#xD;
           provided in the clinic in a liquid form and will be administered every other week,&#xD;
           starting with the Baseline visit, through Week 14. Week 14 is the last double-blind&#xD;
           treatment administration of the study, while Week 16 is the primary time point for&#xD;
           assessment of efficacy. Patients will return to the clinic every other week during the&#xD;
           double blind treatment period.&#xD;
&#xD;
      After completion of the double-blind phase, patients will then return to the clinic 26 weeks&#xD;
      following the last dose of study medication for a safety assessment and stool sample culture.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Well tolerated but failed to demonstrate significant activity. So it did not meet its primary&#xD;
    endpoint or key secondary endpoints.&#xD;
  </why_stopped>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">May 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Aberrant Behavior Checklist (ABC) subscale scores</measure>
    <time_frame>16 weeks</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary assessments of efficacy will be assessed via: The change from baseline in the CY-BOCS, CGI-I, SRS, SCQ.</measure>
    <time_frame>49 weeks</time_frame>
    <description>Secondary assessments of efficacy will be assessed via:&#xD;
• The change from baseline in the Clinical Global Impression - Improvement scale (CGI-I)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Clinical Laboratory</measure>
    <time_frame>49 weeks</time_frame>
    <description>Clinical laboratories will include hematology and serum chemistry panels, as well as C-reactive protein</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Autistic Spectrum Disorders</condition>
  <arm_group>
    <arm_group_label>TSO 2500</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2500 TSO every other week</description>
  </arm_group>
  <arm_group>
    <arm_group_label>7500 TSO</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>7500 TSO every other week</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo every other week.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TSO</intervention_name>
    <description>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</description>
    <arm_group_label>7500 TSO</arm_group_label>
    <arm_group_label>TSO 2500</arm_group_label>
    <other_name>Each dose of 2500 and 7500 active Trichuris suis ova will be provided</other_name>
    <other_name>in 15 mL of aqueous suspension (supplied in 30 mL glass container)</other_name>
    <other_name>or matching placebo administered orally at the investigational center</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females, ages 6 to 17 years, inclusive&#xD;
&#xD;
          2. Diagnosis via Diagnostic and Statistical Manual for Mental Disorders- Forth Edition&#xD;
             (DSM-IV)-and confirmed by Autism Diagnostic Observation&#xD;
&#xD;
             Schedule (ADOSI):&#xD;
&#xD;
          3. CGI-Severity score &gt; 4 and ABC irritability score &gt; 18&#xD;
&#xD;
          4. Mental age of &gt; 18 months&#xD;
&#xD;
          5. Weight of at least ** kg&#xD;
&#xD;
          6. Currently psychotropic medication free or on stable dose of psychotropic medication&#xD;
             for at least 3 months prior to the study.&#xD;
&#xD;
          7. Willing to comply with the schedule of study visits and protocol requirements&#xD;
&#xD;
          8. Patient and/or guardian have the ability to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous diagnosis of Rett's Disorder, Aspergers Disorder, Childhood Disintegrative&#xD;
             Disorder, Fragile X Syndrome, or other disorders on the autism spectrum&#xD;
&#xD;
          2. History of Bipolar Disorder, Psychotic Disorders, or major Depression&#xD;
&#xD;
          3. Seizure within the previous 6 months&#xD;
&#xD;
          4. Patient received antibiotic, antifungal or antiparasitic medication in the last 2&#xD;
             weeks prior to Screening and/or would potentially require this during the study&#xD;
             treatment period&#xD;
&#xD;
          5. Patient with history of drug or alcohol abuse within 6 months prior to Screening&#xD;
&#xD;
          6. Patient with evidence of poor compliance with medical advice and instruction including&#xD;
             diet or medication&#xD;
&#xD;
          7. Patient is unable or unwilling to swallow study medication suspension&#xD;
&#xD;
          8. Patient with a significant medical condition which puts the patient at risk for study&#xD;
             participation and/or for any reason is considered by the Investigator to be an&#xD;
             unsuitable candidate to receive TSO or is potentially put at risk by study procedures&#xD;
&#xD;
          9. Patient who has participated in another clinical trial within 30 days of Screening for&#xD;
             this trial and/or any experimental treatment for this population&#xD;
&#xD;
         10. Females of childbearing potential who are unwilling or unable to use an acceptable&#xD;
             method to avoid pregnancy for the entire study period&#xD;
&#xD;
         11. Females who are pregnant or breastfeeding at the time of enrollment&#xD;
&#xD;
         12. Patients with any of the following laboratory values:&#xD;
&#xD;
               1. White blood cell count ≤ 3,000/mm3 (≤ 3.0 x 109/L) or ≥ 14,000/mm3 (≥14 x 109/L)&#xD;
&#xD;
               2. Platelet count ≤ 100,000/μL (≤100 x 109/L)&#xD;
&#xD;
               3. Serum creatinine ≥ 1.5 mg/dL (≥ 132.6 μmol/L) or &gt;2 x upper limit of normal (ULN)&#xD;
&#xD;
               4. AST (SGOT) or ALT (SGPT) &gt; 2 x ULN&#xD;
&#xD;
               5. Total bilirubin &gt;2 mg/dL (34 μmol/L)&#xD;
&#xD;
               6. Hemoglobin &lt; 9 g/dL&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Itai Berger, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hadassah Medical Organization</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Neuro-Cognitive Center, Pediatric Division, Hadassah-Hebrew University Medical Center</name>
      <address>
        <city>Jerusalem</city>
        <state>Mount Scopus</state>
        <zip>91240</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>15591509</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>21372112</PMID>
  </reference>
  <verification_date>April 2014</verification_date>
  <study_first_submitted>November 19, 2012</study_first_submitted>
  <study_first_submitted_qc>November 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2012</study_first_posted>
  <last_update_submitted>January 31, 2016</last_update_submitted>
  <last_update_submitted_qc>January 31, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 2, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Autism</keyword>
  <keyword>Trichuris Suis Ova</keyword>
  <keyword>Behavior</keyword>
  <keyword>Irritability</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Autistic Disorder</mesh_term>
    <mesh_term>Autism Spectrum Disorder</mesh_term>
    <mesh_term>Child Development Disorders, Pervasive</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01734941
org study id: 0522-12-HMO
nct id: NCT01734941
lead sponsor: 
has dmc: Yes
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)
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Aberrant Behavior Checklist (ABC) subscale scores
time frame: 16 weeks
description: 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.
measure: Secondary assessments of efficacy will be assessed via: The change from baseline in the CY-BOCS, CGI-I, SRS, SCQ.
time frame: 49 weeks
description: Secondary assessments of efficacy will be assessed via:
• The change from baseline in the Clinical Global Impression - Improvement scale (CGI-I)
measure: Clinical Laboratory
time frame: 49 weeks
description: Clinical laboratories will include hematology and serum chemistry panels, as well as C-reactive protein
arm group label: TSO 2500
arm group type: Active Comparator
description: 2500 TSO every other week
arm group label: 7500 TSO
arm group type: Active Comparator
description: 7500 TSO every other week
arm group label: Placebo
arm group type: Placebo Comparator
description: placebo every other week.
intervention type: Drug
intervention name: TSO
description: 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
arm group label: 7500 TSO
arm group label: TSO 2500
other name: Each dose of 2500 and 7500 active Trichuris suis ova will be provided
other name: in 15 mL of aqueous suspension (supplied in 30 mL glass container)
other name: or matching placebo administered orally at the investigational center
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 6 Years
maximum age: 17 Years
healthy volunteers: No
last name: Itai Berger, MD
role: Principal Investigator
affiliation: Hadassah Medical Organization
facility: 
country: Israel
citation: 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.
PMID: 15591509
citation: 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.
PMID: 21372112
responsible party type: Sponsor
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder
mesh term: Child Development Disorders, Pervasive