Xolair Interventional Study in ASD Patients With Comorbid Atopy

Phase 1

Withdrawn

• Conditions: Autism Spectrum Disorder; Atopy
• Interventions: Drug: Omalizumab Injection [Xolair]

• Registration Number: NCT04535817
• Lead Sponsor: Beth Israel Deaconess Medical Center

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 Timeline

• Study First Submitted: 2020-08-13
• Study First Submitted QC: 2020-08-27
• Study First Posted: 2020-09-02
• Study Start: 2021-01-01
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-11
• Last Update Posted: 2021-08-18
• Primary Completion: 2022-01-01
• Study Completion: 2022-01-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Group	Omalizumab Injection [Xolair]	Subjects will receive subcutaneous treatment of 300mg of omalizumab during the 24-week treatment period. One injection will be administered every 4 weeks.

Primary Outcome Measures

Name	Time	Method
Change from Baseline to Week 48 in Social Responsiveness Scale (SRS) Edition 2	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	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 24 in Aberrant Behavior Checklist (ABC)	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 1 in Autism Treatment Evaluation Checklist (ATEC)	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 8 in Autism Treatment Evaluation Checklist (ATEC)	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 24 in Social Responsiveness Scale (SRS) Edition 2	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 16 in Autism Treatment Evaluation Checklist (ATEC)	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)	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 Week 24 to Week 48 in Autism Treatment Evaluation Checklist (ATEC)	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.
Change from Baseline to Week 12 in Social Responsiveness Scale (SRS) Edition 2	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 4 in Autism Treatment Evaluation Checklist (ATEC)	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 24 in Autism Treatment Evaluation Checklist (ATEC)	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 12 in Aberrant Behavior Checklist (ABC)	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 Week 24 to Week 48 in Aberrant Behavior Checklist (ABC)	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 48 in Aberrant Behavior Checklist (ABC)	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 Baseline to Week 12 in Autism Treatment Evaluation Checklist (ATEC)	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 48 in Autism Treatment Evaluation Checklist (ATEC)	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.

Secondary Outcome Measures

Name	Time	Method
Inflammatory Marker Levels	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).
Epworth Sleepiness Scale (ESS)	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.
Structural MRI	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)	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.
Pittsburgh Sleep Quality Index (PSQI)	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)	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)	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.
Generalized Anxiety Disorder 7-item (GAD-7)	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.
Validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD)	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."

Trial Locations

Locations (1)

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States