Xolair Interventional Study in ASD Patients With Comorbid Atopy

The Effect of Omalizumab (Xolair) on Improving Neuropsychiatric Symptoms in a Subset of ASD Patients With Atopic Disease and Elevated Total IgE Levels

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.

Study Overview

• Status: Withdrawn
• Conditions: Autism Spectrum Disorder; Atopy
• Intervention / Treatment: Drug: Omalizumab Injection [Xolair]

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: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Omalizumab Injection [Xolair]; 300mg via 2 subcutaneous injections every 4 weeks; Other Names: Xolair

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline to Week 12 in Social Responsiveness Scale (SRS) Edition 2	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).	Baseline and Week 12
Change from Baseline to Week 24 in Social Responsiveness Scale (SRS) Edition 2	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).	Baseline and Week 24
Change from Baseline to Week 48 in Social Responsiveness Scale (SRS) Edition 2	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).	Baseline and Week 48
Change from Week 24 to Week 48 in Social Responsiveness Scale (SRS) Edition 2	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).	Week 24 (conclusion of treatment period) and Week 48 (follow-up)
Change from Baseline to Week 12 in Aberrant Behavior Checklist (ABC)	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.	Baseline and Week 12
Change from Baseline to Week 24 in Aberrant Behavior Checklist (ABC)	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.	Baseline and Week 24 (conclusion of treatment period)
Change from Baseline to Week 48 in Aberrant Behavior Checklist (ABC)	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.	Baseline and Week 48 (follow-up)
Change from Week 24 to Week 48 in Aberrant Behavior Checklist (ABC)	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.	Week 24 (conclusion of treatment period) and Week 48 (follow-up)
Change from Baseline to Week 1 in Autism Treatment Evaluation Checklist (ATEC)	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.	Baseline and Week 1
Change from Baseline to Week 4 in Autism Treatment Evaluation Checklist (ATEC)	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.	Baseline and Week 4
Change from Baseline to Week 8 in Autism Treatment Evaluation Checklist (ATEC)	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.	Baseline and Week 8
Change from Baseline to Week 12 in Autism Treatment Evaluation Checklist (ATEC)	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.	Baseline and Week 12
Change from Baseline to Week 16 in Autism Treatment Evaluation Checklist (ATEC)	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.	Baseline and Week 16
Change from Baseline to Week 20 in Autism Treatment Evaluation Checklist (ATEC)	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.	Baseline and Week 20
Change from Baseline to Week 24 in Autism Treatment Evaluation Checklist (ATEC)	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.	Baseline and Week 24 (conclusion of treatment period)
Change from Baseline to Week 48 in Autism Treatment Evaluation Checklist (ATEC)	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.	Baseline and Week 48 (follow-up)
Change from Week 24 to Week 48 in Autism Treatment Evaluation Checklist (ATEC)	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.	Week 24 (conclusion of treatment period) and Week 48 (follow-up)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory Marker Levels	Inflammatory marker serum concentration quantification (free IgE, total IgE, interleukin 6, tumor necrosis factor alpha, tryptase).	Baseline, Week 12, and Week 24 (conclusion of treatment period)
Structural MRI	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.	Baseline and Week 24 (conclusion of treatment period)
Functional MRI (resting state)	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.	Baseline, and Week 24 (conclusion of treatment period)
Generalized Anxiety Disorder 7-item (GAD-7)	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.	Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
Epworth Sleepiness Scale (ESS)	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.	Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
Pittsburgh Sleep Quality Index (PSQI)	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.	Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
Asthma Control Test (ACT)	A 5 question patient survey designed to identify patients with poorly controlled asthma based on the symptom severity over the last 4 weeks.	Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
Rhinitis Control Assessment Test (RCAT)	A 6 question patient survey designed to evaluate rhinitis symptom control based on symptom severity and frequency over the past week.	Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
Validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD)	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."	Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impressions Scale - Improvement (CGI-I)	Psychological Clinical Assessment - Conducted by a physician, this 7-point scale characterizes changes in the subject's clinical presentation.	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)
Clinical Global Impressions Scale - Severity (CGI-S)	Psychological Clinical Assessment - Conducted by a physician, this 7-point scale defines severity of the subject's psychopathology.	Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
Autonomic indices 1	Blood volume pulse	Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
Autonomic indices 2	Heart Rate	Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
Autonomic indices 3	Blood oxygen saturation	Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
Autonomic indices 4	Carboxyhemoglobin blood saturation	Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
Autonomic indices 5	Blood pressure	Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Novartis
• Investigators: Principal Investigator: Xue-Jun Kong, MD, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2021
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: August 13, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): September 2, 2020

Study Record Updates

• Last Update Posted (Actual): August 18, 2021
• Last Update Submitted That Met QC Criteria: August 11, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: omalizumab
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: 2020P000753

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no plan to share data with researchers not directly involved in this study and on the research team.

Drug and device information, study documents

• 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