Xolair Interventional Study in ASD Patients With Comorbid Atopy

NCT04535817 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 2020P000753
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Autism Spectrum Disorder; Atopy

Keywords

omalizumab

Outcome Measures

Primary Outcomes (17)

• 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 Outcomes (9)

• Inflammatory Marker Levels

  Baseline, Week 12, and Week 24 (conclusion of treatment period)

• Structural MRI

  Baseline and Week 24 (conclusion of treatment period)

• Functional MRI (resting state)

  Baseline, and Week 24 (conclusion of treatment period)

• 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)

• 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)

Other Outcomes (7)

• Clinical Global Impressions Scale - Improvement (CGI-I)

  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)

  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

  Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)

Study Arms (1)

Treatment Group

EXPERIMENTAL

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]

Interventions

Omalizumab Injection [Xolair] DRUG

300mg via 2 subcutaneous injections every 4 weeks

Also known as: Xolair

Treatment Group

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Novartis: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Autism Spectrum Disorder

Interventions

Omalizumab

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Study Officials

• Xue-Jun Kong, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Investigator

Model Details: Baseline testing, followed by 24-week treatment period, followed by 24-week follow-up period.

Study Record Dates

• First Submitted: August 13, 2020
• First Posted: September 2, 2020
• Study Start: January 1, 2021
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: August 18, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)