Clinical trial NCT04535817: Xolair Interventional Study in ASD Patients With Comorbid Atopy
Official title: The Effect of Omalizumab (Xolair) on Improving Neuropsychiatric Symptoms in a Subset of ASD Patients With Atopic Disease and Elevated Total IgE Levels
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Autism Spectrum Disorder
Atopy
Keywords: omalizumab
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2020-09-02
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Baseline testing, followed by 24-week treatment period, followed by 24-week follow-up period.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline to Week 12 in Social Responsiveness Scale (SRS) Edition 2
timeFrame: Baseline and Week 12
measure: Change from Baseline to Week 24 in Social Responsiveness Scale (SRS) Edition 2
timeFrame: Baseline and Week 24
measure: Change from Baseline to Week 48 in Social Responsiveness Scale (SRS) Edition 2
timeFrame: Baseline and Week 48
measure: Change from Week 24 to Week 48 in Social Responsiveness Scale (SRS) Edition 2
timeFrame: Week 24 (conclusion of treatment period) and Week 48 (follow-up)
measure: Change from Baseline to Week 12 in Aberrant Behavior Checklist (ABC)
timeFrame: Baseline and Week 12
measure: Change from Baseline to Week 24 in Aberrant Behavior Checklist (ABC)
timeFrame: Baseline and Week 24 (conclusion of treatment period)
measure: Change from Baseline to Week 48 in Aberrant Behavior Checklist (ABC)
timeFrame: Baseline and Week 48 (follow-up)
measure: Change from Week 24 to Week 48 in Aberrant Behavior Checklist (ABC)
timeFrame: Week 24 (conclusion of treatment period) and Week 48 (follow-up)
measure: Change from Baseline to Week 1 in Autism Treatment Evaluation Checklist (ATEC)
timeFrame: Baseline and Week 1
measure: Change from Baseline to Week 4 in Autism Treatment Evaluation Checklist (ATEC)
timeFrame: Baseline and Week 4
measure: Change from Baseline to Week 8 in Autism Treatment Evaluation Checklist (ATEC)
timeFrame: Baseline and Week 8
measure: Change from Baseline to Week 12 in Autism Treatment Evaluation Checklist (ATEC)
timeFrame: Baseline and Week 12
measure: Change from Baseline to Week 16 in Autism Treatment Evaluation Checklist (ATEC)
timeFrame: Baseline and Week 16
measure: Change from Baseline to Week 20 in Autism Treatment Evaluation Checklist (ATEC)
timeFrame: Baseline and Week 20
measure: Change from Baseline to Week 24 in Autism Treatment Evaluation Checklist (ATEC)
timeFrame: Baseline and Week 24 (conclusion of treatment period)
measure: Change from Baseline to Week 48 in Autism Treatment Evaluation Checklist (ATEC)
timeFrame: Baseline and Week 48 (follow-up)
measure: Change from Week 24 to Week 48 in Autism Treatment Evaluation Checklist (ATEC)
timeFrame: Week 24 (conclusion of treatment period) and Week 48 (follow-up)
Secondary outcomes:
measure: Inflammatory Marker Levels
timeFrame: Baseline, Week 12, and Week 24 (conclusion of treatment period)
measure: Structural MRI
timeFrame: Baseline and Week 24 (conclusion of treatment period)
measure: Functional MRI (resting state)
timeFrame: Baseline, and Week 24 (conclusion of treatment period)
measure: Generalized Anxiety Disorder 7-item (GAD-7)
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
measure: Epworth Sleepiness Scale (ESS)
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
measure: Asthma Control Test (ACT)
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
measure: Rhinitis Control Assessment Test (RCAT)
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
measure: Validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD)
timeFrame: 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:
measure: Clinical Global Impressions Scale - Improvement (CGI-I)
timeFrame: 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)
measure: Clinical Global Impressions Scale - Severity (CGI-S)
timeFrame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
measure: Autonomic indices 1
timeFrame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
measure: Autonomic indices 2
timeFrame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
measure: Autonomic indices 3
timeFrame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
measure: Autonomic indices 4
timeFrame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
measure: Autonomic indices 5
timeFrame: Baseline, Week 0, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (conclusion of treatment period), and Week 48 (follow-up)
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Xue-Jun Kong, MD
role: PRINCIPAL_INVESTIGATOR
References: