COVID-19 Immunologic Antiviral Therapy With Omalizumab

Covid19 Clinical Trial

— CIAO  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04720612
• Other study ID #: CIAO (2021-7500)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 15, 2021
• Est. completion date: December 16, 2022

Study information

• Verified date: November 2022
• Source: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 16, 2022
• Est. primary completion date: November 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Biological:
• Omalizumab
Single subcutaneous dose of 375mg of omalizumab and standard of care.

Other:
• Placebo
Single subcutaneous dose of normal saline in a syringe identical to that of the omalizumab arm and standard of care.

Locations

Country	Name	City	State
Canada	Research Institute of the McGill University Health Centre	Montreal	Quebec
Canada	Niagara Health - St. Catharine's Sites	Niagara	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
McGill University Health Centre/Research Institute of the McGill University Health Centre

Country where clinical trial is conducted

Canada, 

References & Publications (1)

World Health Organization. WHO R&D Blueprint novel Coronavirus COVID-19 Therapeutic Trial Synopsis. In. Geneva, Switzerland. 2020.

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percent of viral clearance of Omalizumab as compared to the control arm	Evaluation of the virologic efficacy of omalizumab as compared to the control arm as assessed by the percent of subjects with SARS-CoV-2 detectable in OP/NP sample at days 0, 2, 7, 14.	Days 0, 2, 7, 14
Other	Spirometry results: Forced Vital Capacity	Evaluation of forced vital capacity, reported in liters, in both omalizumab and control arms at 6 months.	6 months
Other	Spirometry results : Forced expiratory volume in one second	Evaluation of forced expiratory volume in one second, reported in liters, in both omalizumab and control arms at 6 months.	6 months
Other	Anti-Inflammatory effects of Omalizumab as compared to the control arm	Assessed by measuring cytokine levels, TNF-a, IL-1, IL-6, and IFN-a in picograms per milliliter on days 0, 2, 7, 14.	Days 0, 2, 7, 14
Other	Anti-fibrotic effects of Omalizumab as compared to the control arm	Assessed by measuring TGF-ß level in nanograms per milliliter on days 0, 2, 7, 14.	Days 0, 2, 7, 14
Primary	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	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
Secondary	Duration of Mechanical Ventilation	Outcome reported as duration of mechanical ventilation in each arm.	28 Days
Secondary	Duration of Hospitalization	Outcome reported as the duration of hospitalization of patients in each arm.	28 Days
Secondary	Safety in COVID-19 patients	Outcome reported as the number of adverse events and serious adverse events that occurred in each arm.	14 Days
Secondary	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