Clinical trial NCT04720612: COVID-19 Immunologic Antiviral Therapy With Omalizumab
Official title: COVID-19 Immunologic Antiviral Therapy With Omalizumab - An Adaptive Phase II Randomized-Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Covid19
Keywords: Omalizumab
Interferon-alpha
COVID-19
SARS-CoV-2
Coronavirus
Corona virus
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
First posted: 2021-01-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate if omalizumab is effective in decreasing mortality in severe hospitalized COVID-19 cases.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Positive RT-PCR assay for SARS-CoV-2;
2. COVID-19 disease requiring hospitalization
3. 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)
4. Age ≥18 years;
5. 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:

1. Known hypersensitivity to Omalizumab or its excipients
2. Inability to give consent themselves or via proxy
3. Patients who received Omalizumab or another anti-IgE molecule in the last 12 months
4. 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.
5. Patients who are below the age of 18

Primary outcomes:
measure: Incidence of Death or Mechanical Ventilation
timeFrame: 14 Days
Secondary outcomes:
measure: Time to Clinical Improvement
timeFrame: 28 Days
measure: Duration of Mechanical Ventilation
timeFrame: 28 Days
measure: Duration of Hospitalization
timeFrame: 28 Days
measure: Safety in COVID-19 patients
timeFrame: 14 Days
measure: Incidence of All-Cause in Hospital Mortality
timeFrame: 28 Days
Other outcomes:
measure: Percent of viral clearance of Omalizumab as compared to the control arm
timeFrame: Days 0, 2, 7, 14
measure: Spirometry results: Forced Vital Capacity
timeFrame: 6 months
measure: Spirometry results : Forced expiratory volume in one second
timeFrame: 6 months
measure: Anti-Inflammatory effects of Omalizumab as compared to the control arm
timeFrame: Days 0, 2, 7, 14
measure: Anti-fibrotic effects of Omalizumab as compared to the control arm
timeFrame: Days 0, 2, 7, 14
Locations:
city: Niagara
country: Canada
facility: Niagara Health - St. Catharine's Sites
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Research Institute of the McGill University Health Centre
state: Quebec
Study officials:
affiliation: RI-MUHC
name: Elena Netchiporouk, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: World Health Organization. WHO R&D Blueprint novel Coronavirus COVID-19 Therapeutic Trial Synopsis. In. Geneva, Switzerland. 2020.