Treatment of Moderate to Severe Coronavirus Disease (COVID-19) in Hospitalized Patients

Investigational medications adjunct to clinical standard of care treatment will be assessed to evaluate safety and effectiveness as an anti-COVID-19 treatment. All hospitalized persons with moderate to severe COVID-19 disease that meet eligibility criteria will be offered participation.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: Baricitinib (janus kinase inhibitor); Drug: Remdesivir (antiviral); Drug: Remdesivir (antiviral) + barictinib (janus kinase inhibitor); Drug: Tocilizumab (interleukin 6 inhibitor)

• Study Type: Interventional
• Enrollment (Actual): 363
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Health Authority

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18 years or older
• Moderate to severe COVID-19 associated disease as defined by the WHO
• Willing and able to provide informed consent prior to performing study procedures
• Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay
• Illness of any duration, and at least one of the following: Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), or Clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤ 94% on room air, or Require mechanical ventilation and/or supplemental oxygen.
• Normal potassium, magnesium, and calcium levels pre-therapy when used in agents at risk of QT prolongation

Patients will be further distinguished based on their disease severity into one of two categories:

• Moderate and severe, not critical disease: patients with SpO2 ≤ 94% on room air, and those who require supplemental oxygen
• Severe, critical disease: patients with critical illness requiring ICU-level care including requiring mechanical ventilation or ECMO, and/or end organ dysfunction as seen in sepsis/septic shock.

Exclusion Criteria:

• Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 X upper limit of normal (ULN)
• Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive study treatment Medication specific Exclusion

Baricitinib:

1. Contraindicated for patients with known hypersensitivity to baricitinib or to any of the excipients.
2. Prior untreated latent tuberculosis
3. Any individuals with TB risk factors will not be enrolled in the baricitinib arm of the study.
4. Presence of active viral hepatitis C or B
5. People with a clinical history of invasive or active fungal infection
6. People with a clinical history of active CMV disease in the last year
7. Patients who are pregnant or breastfeeding
8. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <15)

Tocilizumab:

1. Known hypersensitivity to tocilizumab or any of its components
2. Prior untreated latent tuberculosis
3. Any individuals with TB risk factors will not be enrolled in the tocilizumab arm of the study.
4. Presence of active viral hepatitis C or B
5. People with a clinical history of invasive or active fungal infection
6. People with a clinical history of active CMV disease in the last year
7. CRP<75 mg/L
8. SpO2 ≥ 92% on room air

Remdesivir:

1. Known hypersensitivity to remdesivir or any of its components
2. Weight below 40 kg
3. SpO2 ≥ 94% on room air
4. Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR <30)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Baricitinib; Moderate and severe, not critical disease	Drug: Baricitinib (janus kinase inhibitor); Baricitinib will be administered as 4 mg po daily for 14 days or until hospital discharge, whichever is sooner.
Experimental: Remdesivir; Moderate and severe, not critical disease	Drug: Remdesivir (antiviral); Remdesivir will be administered as a loading dose of 200 mg IV over one hour on day 1 followed by 100 mg IV daily over one hour on days 2-5 (with a possibility to extend to up to 10 days total).
Experimental: Remdesivir + baricitinib; Moderate and severe, not critical disease	Drug: Remdesivir (antiviral) + barictinib (janus kinase inhibitor); Remdesivir will be administered as a loading dose of 200 mg IV over one hour on day 1 followed by 100 mg IV daily over one hour on days 2-5 (with a possibility to extend to up to 10 days total). Baricitinib will be administered as 4 mg po daily for 14 days or until hospital discharge, whichever is sooner.
Experimental: Tocilizumab; Severe, critical disease	Drug: Tocilizumab (interleukin 6 inhibitor); Tocilizumab will be administered as a single IV infusion over one hour. Dosage will be 8 mg/kg total bodyweight up to a maximum of 800 mg.
No Intervention: Clinical standard of care; Moderate and severe, not critical disease AND severe, critical disease as applicable

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical status of subject at day 15 (on a 7 point ordinal scale).	Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities;; Hospitalized, not requiring supplemental oxygen;; Hospitalized, requiring supplemental oxygen;; Hospitalized, on non-invasive ventilation or high flow oxygen devices;; Hospitalized, on invasive mechanical ventilation or ECMO;; Death.	Up to 15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Status on an ordinal scale assessed daily while hospitalized and on days 15 and 29 and 180.	Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities;; Hospitalized, not requiring supplemental oxygen;; Hospitalized, requiring supplemental oxygen;; Hospitalized, on non-invasive ventilation or high flow oxygen devices;; Hospitalized, on invasive mechanical ventilation or ECMO;; Death.	Up to 180 days
Length of time to clinical improvement	Time to clinical improvement is defined as the time to normalization of respiratory rate, fever, and oxygen saturation, and alleviation of cough within 72 hours.	Up to 29 days
Number of participants with normal pulmonary function and normal O2 saturation on days 11, 15 and 29		Up to 29 days
Number of participants that developed Acute Respiratory Distress Syndrome (ARDS) after treatment		Up to 24 weeks
Length of time to clinical progression	Time to clinical progression, defined as the time to death, mechanical ventilation, or ICU admission	Up to 29 days
Cause of death (if applicable)		Up to 24 weeks
Sequential Organ Failure Assessment (SOFA) score, daily while hospitalized and on days 15 and 29. (Initial, highest, deltas and mean)		Up to 29 days
Length of time to normalization of fever	Fever normalization as defined by: Temperature < 36.6 °C armpit, < 37.2 °C oral, or < 37.8 °C rectal sustained for minimum 24 hours	Up to 29 days
Length of time to normalization of oxygen saturation	Oxygen normalization as defined by: peripheral capillary oxygen saturation (Sp02) > 94% sustained minimum 24 hours.	Up to 29 days
Duration of supplemental oxygen (if applicable)		Up to 29 days
Duration of mechanical ventilation (if applicable)		Up to 29 days
Duration of hospitalization		Up to 29 days
Adverse events		Up to 180 days

Other Outcome Measures

Outcome Measure	Time Frame
Global and SARS-CoV-2-specific immune responses before, during and after intervention and in standard of care treatment arm	Up to 180 days

Collaborators and Investigators

• Sponsor: Lisa Barrett
• Collaborators: Nova Scotia Health Authority; Dalhousie University

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2020
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: March 24, 2020
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: September 15, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID; coronavirus
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites; Protein Kinase Inhibitors; Antiviral Agents; Remdesivir; Janus Kinase Inhibitors
• Other Study ID Numbers: SAIL-004

Drug and device information, study documents

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