COVID-19 Immunologic Antiviral Therapy With Omalizumab

Study Overview
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Brief Summary
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To evaluate if omalizumab is effective in decreasing mortality in severe hospitalized COVID-19 cases.

Detailed Description
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Coronavirus disease 2019 (COVID-19) has affected over 88 million people, resulting in the death of at least 1.9 million individuals and numbers continue to climb exponentially. Despite these staggering numbers, there are currently very few effective treatments for COVID-19. The immune response to COVID-19 virus appears to follow 2 phases. During the incubation and early disease, interferon (ex. INF-α) signaling and adaptive immunity preclude the disease from progressing. If, and when, this immune response is impaired, the virus may cause pathologic inflammation leading to massive organ dysfunction leading to acute respiratory distress syndrome (ARDS). Omalizumab is a humanized anti-IgE antibody approved by Health Canada for the treatment of moderate-severe asthma and chronic spontaneous urticaria. Omalizumab has been shown to exhibit antiviral and anti-inflammatory effects in virally exacerbated asthma cases that may be relevant to the treatment of COVID-19. This is a double blind randomized placebo-controlled trial to evaluate the efficacy of a single dose of omalizumab in reducing all cause mortality at day 29 in severe hospitalized COVID-19 cases. Moreover, time to improvement/hospital discharge, incidence and duration of mechanical ventilation and safety will be assessed.

Official Title
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COVID-19 Immunologic Antiviral Therapy With Omalizumab - An Adaptive Phase II Randomized-Controlled Clinical Trial

Conditions
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Covid19

Intervention / Treatment
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* Biological: Omalizumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive RT-PCR assay for SARS-CoV-2; COVID-19 disease requiring hospitalization Dyspnea at rest or during minimal activity (sitting, talking, coughing, swallowing), OR Respiratory rate > 22/min, OR PaO2 < 65mmHg or O2Sat < 90%, OR Infiltrate on chest radiography (CXR) (worsening CXR if baseline abnormal) Age ≥18 years; Ability to provide consent or to provide consent via a substitute decision maker Patients who are pregnant may also be eligible if consent is provided. Patients who have received one of the SARS-CoV2 vaccines and/or bamlanivimab are eligible to participate in the study Exclusion Criteria: Known hypersensitivity to Omalizumab or its excipients Inability to give consent themselves or via proxy Patients who received Omalizumab or another anti-IgE molecule in the last 12 months Patients receiving another monoclonal antibody to treat SARS-CoV-2/other indication prior to starting CIAO trial. However, once the study is initiated, if it is judged by the treating team/patient's doctor that patient's health/clinical status may benefit from a monoclonal antibody (e.g. tocilizumab), this will be allowed. Patients who are below the age of 18

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omalizumab<br>Participants in this arm will receive the study drug, omalizumab. | Biological: Omalizumab<br>* Single subcutaneous dose of 375mg of omalizumab and standard of care.<br>* Other names: Xolair;|
| Placebo Comparator: Placebo<br>Participants in this arm will receive a placebo treatment. | Other: Placebo<br>* Single subcutaneous dose of normal saline in a syringe identical to that of the omalizumab arm and standard of care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Death or Mechanical Ventilation | Outcome reported as the number of patients in each arm that either experience death by any cause or mechanical ventilation. | 14 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Clinical Improvement | Outcome reported as the time to improvement of 2 points on the 8-category ordinal scale. (World Health Organization, 2020) 8-category ordinal scale: 0- Uninfected, no clinical or virological evidence of infection Ambulatory, no limitation of activities Ambulatory, limitation of activities Hospitalized mild disease, no oxygen therapy Hospitalized mild disease, oxygen by mask or nasal prongs Hospitalized severe disease, non invasive ventilation or high-flow oxygen Hospitalized severe disease, intubation and mechanical ventilation Hospitalized severe disease, ventilation + additional organ support - pressors, RRT, ECMO Death | 28 Days | 
| Duration of Mechanical Ventilation | Outcome reported as duration of mechanical ventilation in each arm. | 28 Days | 
| Duration of Hospitalization | Outcome reported as the duration of hospitalization of patients in each arm. | 28 Days | 
| Safety in COVID-19 patients | Outcome reported as the number of adverse events and serious adverse events that occurred in each arm. | 14 Days | 
| Incidence of All-Cause in Hospital Mortality | Outcome reported as the number of patients in each arm that experience death by any cause while in hospital. | 28 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Omalizumab, Interferon-alpha, SARS-CoV-2, Coronavirus, Corona virus