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Xolair Interventional Study in ASD Patients With Comorbid Atopy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04535817
Recruitment Status : Withdrawn (We are terminating due to loss of funding because of Covid-19.)
First Posted : September 2, 2020
Last Update Posted : August 18, 2021
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Xue-Jun Kong, Beth Israel Deaconess Medical Center

Tracking Information
First Submitted Date  ICMJE August 13, 2020
First Posted Date  ICMJE September 2, 2020
Last Update Posted Date August 18, 2021
Estimated Study Start Date  ICMJE January 1, 2021
Estimated Primary Completion Date January 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 27, 2020)
  • Change from Baseline to Week 12 in Social Responsiveness Scale (SRS) Edition 2 [ Time Frame: Baseline and Week 12 ]
    Social communication and behavior - The scoring is based on T-score which is based on the sum of responses as follows (76 to higher - severe, 66 to 75- moderate deficiencies, 60 to 65 - mild deficiencies, 59 and below is not clinically significant for ASD).
  • Change from Baseline to Week 24 in Social Responsiveness Scale (SRS) Edition 2 [ Time Frame: Baseline and Week 24 ]
    Social communication and behavior - The scoring is based on T-score which is based on the sum of responses as follows (76 to higher - severe, 66 to 75- moderate deficiencies, 60 to 65 - mild deficiencies, 59 and below is not clinically significant for ASD).
  • Change from Baseline to Week 48 in Social Responsiveness Scale (SRS) Edition 2 [ Time Frame: Baseline and Week 48 ]
    Social communication and behavior - The scoring is based on T-score which is based on the sum of responses as follows (76 to higher - severe, 66 to 75- moderate deficiencies, 60 to 65 - mild deficiencies, 59 and below is not clinically significant for ASD).
  • Change from Week 24 to Week 48 in Social Responsiveness Scale (SRS) Edition 2 [ Time Frame: Week 24 (conclusion of treatment period) and Week 48 (follow-up) ]
    Social communication and behavior - The scoring is based on T-score which is based on the sum of responses as follows (76 to higher - severe, 66 to 75- moderate deficiencies, 60 to 65 - mild deficiencies, 59 and below is not clinically significant for ASD).
  • Change from Baseline to Week 12 in Aberrant Behavior Checklist (ABC) [ Time Frame: Baseline and Week 12 ]
    Social behavior test - The total score is calculated based on 5 sub-scales (Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactive/Noncompliance, and Inappropriate Speech). There are 58 questions that are scored on a 0-3 scale 0 -"not at all 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". Based on this sub-scores are calculated and added to get the total score.
  • Change from Baseline to Week 24 in Aberrant Behavior Checklist (ABC) [ Time Frame: Baseline and Week 24 (conclusion of treatment period) ]
    Social behavior test - The total score is calculated based on 5 sub-scales (Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactive/Noncompliance, and Inappropriate Speech). There are 58 questions that are scored on a 0-3 scale 0 -"not at all 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". Based on this sub-scores are calculated and added to get the total score.
  • Change from Baseline to Week 48 in Aberrant Behavior Checklist (ABC) [ Time Frame: Baseline and Week 48 (follow-up) ]
    Social behavior test - The total score is calculated based on 5 sub-scales (Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactive/Noncompliance, and Inappropriate Speech). There are 58 questions that are scored on a 0-3 scale 0 -"not at all 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". Based on this sub-scores are calculated and added to get the total score.
  • Change from Week 24 to Week 48 in Aberrant Behavior Checklist (ABC) [ Time Frame: Week 24 (conclusion of treatment period) and Week 48 (follow-up) ]
    Social behavior test - The total score is calculated based on 5 sub-scales (Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactive/Noncompliance, and Inappropriate Speech). There are 58 questions that are scored on a 0-3 scale 0 -"not at all 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". Based on this sub-scores are calculated and added to get the total score.
  • Change from Baseline to Week 1 in Autism Treatment Evaluation Checklist (ATEC) [ Time Frame: Baseline and Week 1 ]
    Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity.
  • Change from Baseline to Week 4 in Autism Treatment Evaluation Checklist (ATEC) [ Time Frame: Baseline and Week 4 ]
    Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity.
  • Change from Baseline to Week 8 in Autism Treatment Evaluation Checklist (ATEC) [ Time Frame: Baseline and Week 8 ]
    Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity.
  • Change from Baseline to Week 12 in Autism Treatment Evaluation Checklist (ATEC) [ Time Frame: Baseline and Week 12 ]
    Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity.
  • Change from Baseline to Week 16 in Autism Treatment Evaluation Checklist (ATEC) [ Time Frame: Baseline and Week 16 ]
    Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity.
  • Change from Baseline to Week 20 in Autism Treatment Evaluation Checklist (ATEC) [ Time Frame: Baseline and Week 20 ]
    Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity.
  • Change from Baseline to Week 24 in Autism Treatment Evaluation Checklist (ATEC) [ Time Frame: Baseline and Week 24 (conclusion of treatment period) ]
    Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity.
  • Change from Baseline to Week 48 in Autism Treatment Evaluation Checklist (ATEC) [ Time Frame: Baseline and Week 48 (follow-up) ]
    Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity.
  • Change from Week 24 to Week 48 in Autism Treatment Evaluation Checklist (ATEC) [ Time Frame: Week 24 (conclusion of treatment period) and Week 48 (follow-up) ]
    Social Behavior Test - The total score is calculated by adding together the scores of 4 subtests (Speech/Language Communication, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior). This 67 question test will provide scores for each subtest and a total score, for which a higher score indicates greater symptom severity.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2020)
  • Inflammatory Marker Levels [ Time Frame: Baseline, Week 12, and Week 24 (conclusion of treatment period) ]
    Inflammatory marker serum concentration quantification (free IgE, total IgE, interleukin 6, tumor necrosis factor alpha, tryptase).
  • Structural MRI [ Time Frame: Baseline and Week 24 (conclusion of treatment period) ]
    The software Freesurfer will be used to calculate volume of brain regions and diffusion parameters (e.g. fractional anisotropy and mean diffusivity) from structural T1 and diffusion tensor images respectively. Paired t-test will be used to compare brain volume at baseline and post-treatment.
  • Functional MRI (resting state) [ Time Frame: Baseline, and Week 24 (conclusion of treatment period) ]
    Correlation analysis will be used to calculate the connectivity across different brain regions. Paired t-test will be used to compare differences in activity at baseline and post-treatment.
  • Generalized Anxiety Disorder 7-item (GAD-7) [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    Anxiety symptom questionnaire - Scoring is based on how frequently the subject experienced 7 GAD-related symptoms in the last two weeks. Each question is rated on a 0-3 scale: 0 - "Not at all", 1 - "Several days", 2 - "More than half the days", 3 - "Nearly every day." Defined cutoffs will be used to define severity.
  • Epworth Sleepiness Scale (ESS) [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    Sleepiness Questionnaire - Scoring is based on how likely the subject is to doze off or fall asleep during 8 daily activities. Higher scores indicate more severe sleepiness.
  • Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    Sleep Quality Questionnaire - Scoring is based on 19 self-administered questions and 5 roommate questions. An algorithm provided with the questionnaire will be used to calculate global sleep quality score, for which a higher score indicates greater severity.
  • Asthma Control Test (ACT) [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    A 5 question patient survey designed to identify patients with poorly controlled asthma based on the symptom severity over the last 4 weeks.
  • Rhinitis Control Assessment Test (RCAT) [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    A 6 question patient survey designed to evaluate rhinitis symptom control based on symptom severity and frequency over the past week.
  • Validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    A clinical assessment tool used to describe severity of atopic dermatitis. The vIGA-AD includes a single scale from 0-4, in which 0 is "clear" and 4 is "severe."
Original Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2020)
  • Inflammatory Marker Levels [ Time Frame: Baseline, Week 12, and Week 24 (conclusion of treatment period) ]
    Inflammatory marker serum concentration quantification (free IgE, total IgE, interleukin 6, tumor necrosis factor alpha, tryptase).
  • Structural MRI [ Time Frame: Baseline and Week 24 (conclusion of treatment period) ]
    The software Freesurfer will be used to calculate volume of brain regions and diffusion parameters (e.g. fractional anisotropy and mean diffusivity) from structural T1 and diffusion tensor images respectively. Paired t-test will be used to compare brain volume at baseline and post-treatment.
  • Functional MRI (resting state) [ Time Frame: Baseline, and Week 24 (conclusion of treatment period) ]
    Correlation analysis will be used to calculate the connectivity across different brain regions. Paired t-test will be used to compare differences in activity at baseline and post-treatment.
  • Generalized Anxiety Disorder 7-item (GAD-7) [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    Anxiety symptom questionnaire - Scoring is based on how frequently the subject experienced 7 GAD-related symptoms in the last two weeks. Each question is rated on a 0-3 scale: 0 - "Not at all", 1 - "Several days", 2 - "More than half the days", 3 - "Nearly every day." Defined cutoffs will be used to define severity.
  • Epworth Sleepiness Scale (ESS) [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    Sleepiness Questionnaire - Scoring is based on how likely the subject is to doze off or fall asleep during 8 daily activities. Higher scores indicate more severe sleepiness.
  • Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    Sleep Quality Questionnaire - Scoring is based on 19 self-administered questions and 5 roommate questions. An algorithm provided with the questionnaire will be used to calculate global sleep quality score, for which a higher score indicates greater severity.
  • Self Report Measure of Atopic Disease Symptoms [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    Patient will be asked to rate their atopic disease symptoms on a scale from 1-10 based on their perception of their severity.
Current Other Pre-specified Outcome Measures
 (submitted: August 27, 2020)
  • Clinical Global Impressions Scale - Improvement (CGI-I) [ Time Frame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    Psychological Clinical Assessment - Conducted by a physician, this 7-point scale characterizes changes in the subject's clinical presentation.
  • Clinical Global Impressions Scale - Severity (CGI-S) [ Time Frame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    Psychological Clinical Assessment - Conducted by a physician, this 7-point scale defines severity of the subject's psychopathology.
  • Autonomic indices 1 [ Time Frame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    Blood volume pulse
  • Autonomic indices 2 [ Time Frame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    Heart Rate
  • Autonomic indices 3 [ Time Frame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    Blood oxygen saturation
  • Autonomic indices 4 [ Time Frame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    Carboxyhemoglobin blood saturation
  • Autonomic indices 5 [ Time Frame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up) ]
    Blood pressure
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Xolair Interventional Study in ASD Patients With Comorbid Atopy
Official Title  ICMJE The Effect of Omalizumab (Xolair) on Improving Neuropsychiatric Symptoms in a Subset of ASD Patients With Atopic Disease and Elevated Total IgE Levels
Brief Summary Following the publication of two case studies that reported behavioral benefit in ASD patients treated with omalizumab, the investigators will conduct a pilot trial to test the proof-of-concept efficacy of omalizumab in ASD patients with comorbid atopic disease. Investigators will evaluate behavioral improvement using three questionnaires. Investigators will also perform fMRI on all subjects and obtain serum samples for quantification of immunological biomarkers. If the trial is conclusive, the investigators will conduct a larger-scale, randomized-controlled trial to further understand the pathology of allergy in this subpopulation of ASD patients and the efficacy of this intervention.
Detailed Description This clinical trial is a Phase I, single-arm, open-label study. All 20 subjects will be given the same dosage of the study drug. Following baseline testing, subjects will undergo treatment during a 24 week treatment period and will receive six subcutaneous injections total, one injection every 4 weeks. A 24-week follow-up period after the treatment period will be concluded with patient interview. Behavioral questionnaires will be administered throughout the duration of the trial. fMRI will be conducted at baseline and at the conclusion of the treatment period. Blood will be drawn for serum testing at baseline, at Week 12 during the treatment period, and at the conclusion of the treatment period. Vitals and CGI will also be assessed throughout the trial.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Baseline testing, followed by 24-week treatment period, followed by 24-week follow-up period.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Autism Spectrum Disorder
  • Atopy
Intervention  ICMJE Drug: Omalizumab Injection [Xolair]
300mg via 2 subcutaneous injections every 4 weeks
Other Name: Xolair
Study Arms  ICMJE Experimental: Treatment Group
Subjects will receive subcutaneous treatment of 300mg of omalizumab during the 24-week treatment period. One injection will be administered every 4 weeks.
Intervention: Drug: Omalizumab Injection [Xolair]
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: August 11, 2021)
0
Original Estimated Enrollment  ICMJE
 (submitted: August 27, 2020)
20
Estimated Study Completion Date  ICMJE January 1, 2022
Estimated Primary Completion Date January 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Age between 18-30 years old.
  • Clinical diagnosis of ASD during childhood that is still active.
  • History of atopic diseases, including asthma, atopic dermatitis, and allergic rhinitis.
  • Total serum IgE level ≥ 30 IU/ml and ≤ 400 IU/ml

Exclusion criteria:

  • History of omalizumab use.
  • Subjects who have used oral or systemic steroid burst within 6 weeks of study enrollment. Subjects who are receiving a maintenance dose of Prednisone of 5 mg/day or less will be allowed provided the dose of Prednisone is not changed during the study.
  • Subjects actively taking the antipsychotic medication, Loxapine.
  • History of cancer or pre-cancer.
  • Subjects with active or unstable seizure disorder.
  • History or active signs of psychosis.
  • Body weight > 90kg
  • For subjects who meet allergic rhinitis inclusion criteria, RCAT >20
  • IQ < 70
  • Adaptive Behavior Composite score < 90, based on the Vineland 3rd Edition
  • Lactating or pregnant females. Xolair has not been sufficiently tested for safe use in pregnant females.
  • Subjects who are deemed by the study staff to be unable to cooperate with or understand the instructions that will be given during the study.
  • Subjects with severe medical condition(s) that in the view of a Physician Investigator prohibits participation in the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 30 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04535817
Other Study ID Numbers  ICMJE 2020P000753
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: There is no plan to share data with researchers not directly involved in this study and on the research team.
Current Responsible Party Xue-Jun Kong, Beth Israel Deaconess Medical Center
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Beth Israel Deaconess Medical Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Novartis
Investigators  ICMJE
Principal Investigator: Xue-Jun Kong, MD Beth Israel Deaconess Medical Center
PRS Account Beth Israel Deaconess Medical Center
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP