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

NCT04321993 | Unknown Phase 2

• 1 other identifier: SAIL-004
• Study Type: interventional
• Target: 363
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

COVID-19

Keywords

COVID; coronavirus; SARS-CoV-2

Outcome Measures

Primary Outcomes (1)

• Clinical status of subject at day 15 (on a 7 point ordinal scale).

  1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death.

  Up to 15 days

Secondary Outcomes (13)

• Status on an ordinal scale assessed daily while hospitalized and on days 15 and 29 and 180.

  Up to 180 days

• Length of time to clinical improvement

  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

  Up to 29 days

Other Outcomes (1)

• Global and SARS-CoV-2-specific immune responses before, during and after intervention and in standard of care treatment arm

  Up to 180 days

Study Arms (5)

Baricitinib

EXPERIMENTAL

Moderate and severe, not critical disease

Drug: Baricitinib (janus kinase inhibitor)

Remdesivir

EXPERIMENTAL

Moderate and severe, not critical disease

Drug: Remdesivir (antiviral)

Remdesivir + baricitinib

EXPERIMENTAL

Moderate and severe, not critical disease

Drug: Remdesivir (antiviral) + barictinib (janus kinase inhibitor)

Tocilizumab

EXPERIMENTAL

Severe, critical disease

Drug: Tocilizumab (interleukin 6 inhibitor)

Clinical standard of care

NO INTERVENTION

Moderate and severe, not critical disease AND severe, critical disease as applicable

Interventions

Baricitinib (janus kinase inhibitor) DRUG

Baricitinib will be administered as 4 mg po daily for 14 days or until hospital discharge, whichever is sooner.

Baricitinib

Remdesivir (antiviral) + barictinib (janus kinase inhibitor) DRUG

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.

Remdesivir + baricitinib

Remdesivir (antiviral) DRUG

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).

Remdesivir

Tocilizumab (interleukin 6 inhibitor) DRUG

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.

Tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 X upper limit of normal (ULN)
• Baricitinib:
• Contraindicated for patients with known hypersensitivity to baricitinib or to any of the excipients.
• Prior untreated latent tuberculosis
• Any individuals with TB risk factors will not be enrolled in the baricitinib arm of the study.
• Presence of active viral hepatitis C or B
• People with a clinical history of invasive or active fungal infection
• People with a clinical history of active CMV disease in the last year
• Patients who are pregnant or breastfeeding
• Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR \<15)
• Tocilizumab:
• Known hypersensitivity to tocilizumab or any of its components
• Prior untreated latent tuberculosis
• Any individuals with TB risk factors will not be enrolled in the tocilizumab arm of the study.
• Presence of active viral hepatitis C or B

Sponsors & Collaborators

• Lisa Barrett: lead
• Nova Scotia Health Authority: collaborator
• Dalhousie University: collaborator

Study Sites (1)

Nova Scotia Health Authority

Halifax, Nova Scotia, B3H 1V7, Canada

Location

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

baricitinib; Janus Kinase Inhibitors; remdesivir; Antiviral Agents; tocilizumab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Anti-Infective Agents; Therapeutic Uses

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinician Scientist

Study Record Dates

• First Submitted: March 24, 2020
• First Posted: March 26, 2020
• Study Start: April 17, 2020
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: September 18, 2023

Record last verified: 2023-09

Locations

CA (1)