COVID-19 Immunologic Antiviral Therapy With Omalizumab (CIAO)

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Covid19
• Intervention / Treatment: Biological: Omalizumab; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Niagara, Ontario, Canada, L2S 0A9
      • Niagara Health - St. Catharine's Sites
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H4A3J1
      • Research Institute of the McGill University Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Spirometry results: Forced Vital Capacity	Evaluation of forced vital capacity, reported in liters, in both omalizumab and control arms at 6 months.	6 months
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
Anti-Inflammatory effects of Omalizumab as compared to the control arm	Assessed by measuring cytokine levels, TNF-α, IL-1, IL-6, and IFN-α in picograms per milliliter on days 0, 2, 7, 14.	Days 0, 2, 7, 14
Anti-fibrotic effects of Omalizumab as compared to the control arm	Assessed by measuring TGF-β level in nanograms per milliliter on days 0, 2, 7, 14.	Days 0, 2, 7, 14

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Investigators: Principal Investigator: Elena Netchiporouk, MD, MSc, RI-MUHC

Publications and helpful links

General Publications

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

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2021
• Primary Completion (Actual): November 7, 2022
• Study Completion (Anticipated): December 16, 2022

Study Registration Dates

• First Submitted: January 13, 2021
• First Submitted That Met QC Criteria: January 20, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): November 16, 2022
• Last Update Submitted That Met QC Criteria: November 14, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Coronavirus; COVID-19; Interferon-alpha; Omalizumab; Corona virus
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: CIAO (2021-7500)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No