Joint European Research on active and emerging pandemics

Phase 1

• Conditions: SARS-CoV infection; MedDRA version: 23.0Level: PTClassification code 10084268Term: COVID-19System Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2021-000541-41-IT
• Lead Sponsor: OSLO UNIVERSITETSSYKEHUS HF

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-17
• Last Update Posted: 24 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 2000

Inclusion Criteria

Master Protocol Number: 1.1 dated 07 April 2021:
Participants are eligible to be included in the study only if all the following general inclusion (GI) criteria apply:
GI1. >= 18 years of age
GI2. Laboratory-confirmed SARS-CoV-2 infection (new infection or reinfection) as determined by PCR not more than 9 days old
GI3. Admitted to hospital
GI4. Informed consent by the participant or legally authorized representative.
GI5A: Moderate disease state defined as hospitalised patients without oxygen therapy or oxygen by mask or nasal prongs needed, or
GI5B: Severe/critical disease state defined as fulfilliing at least one of the following criteria:
1.SpO2<90% on room air, or
2.SpO2 90-94% with a downwards trend and/or signs of respiratory distress*, or
3.Need of oxygen by NIV (CPAP, BIPAP), high flow or non-rebreather mask, or
4.Need of mechanical ventilation/ECMO
*persistently increased respiratory rate, use of accessory muscles, inability to complete full sentences. Clinical judgement must be applied to determine whether a low oxygen saturation is indicative of disease progression or severity or is habitual for a given patient (i.e., with underlying chronic lung disease).
NIV=non-invasive ventilation. CPAP= Continuous Positive Airway Pressure, BPAP= Bi-level Positive Airway Pressure, ECMO = Extracorporeal membrane oxygenation.
Additional inclusion criteria are given in the intervention-specific sub-protocols.

Baricitinib specific protocol v. 1.1 dated 07 April 2021:
All participants must be eligible according to the master protocol inclusion criteria (SolidAct Part B).
Only the general inclusion criteria (GI) for severe/critical COVID-19 are applicable:
GI1.>=18 years of age
GI2.Laboratory-confirmed SARS-CoV-2 infection (new infection or reinfection) as determined by PCR in any specimen not more than 9 days old
GI3.Admitted to hospital
GI4.Informed consent by the participant or legally authorized representative.
GI5B: Severe/critical disease state defined as fulfilling at least one of the following criteria:
1.SpO2<90% on room air, or
2.SpO2 90-94% with a downwards trend and/or signs of respiratory distress*, or
3.Need of oxygen by NIV (CPAP, BIPAP), high flow or non-rebreather mask, or
4.Need of mechanical ventilation/ECMO
*persistently increased respiratory rate, use of accessory muscles, inability to complete full sentences. Clinical judgement must be applied to determine whether a low oxygen saturation is indicative of disease progression or severity or is habitual for a given patient (i.e., with underlying chronic lung disease).
NIV=non-invasive ventilation. CPAP= Continuous Positive Airway Pressure, BPAP= Bi-level Positive Airway Pressure, ECMO = extracorporeal membrane oxygenation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1000

Exclusion Criteria

Master Protocol Number 1.1 dated 07 April 2021:
Participants are excluded from the study if any of the following general exclusion criteria apply:
GE1.Anticipated transfer to another non-trial hospital within 72 hours
Additional exclusion criteria, included prohibited medication, confounding trials and details on contraception and pregnancy are given in the intervention-specific sub-protocols.

Baricitinib specific protocol v. 1.1 dated 07 April 2021:
GE1. Anticipated transfer to another non-trial hospital within 72 hours.

In addition, participants are excluded from being eligible for the intervention cohort if any of the additional specific exclusion (SE) criteria below apply:
• SE-01. Receiving cytotoxic or biologic treatments (such as tumour necrosis factor [TNF] inhibitors, anti-interleukin-1 [IL-1, e.g. anakinra], anti-IL-6 [e.g. tocilizumab or sarilumab], T-cell or B-cell targeted therapies (e.g. rituximab), interferon, or Janus kinase (JAK) inhibitors (including baricitinib) for any indication at study entry.
• SE-02. Have received high dose corticosteroids at doses >20 mg prednisone (or prednisone equivalent) per day administered for =14 consecutive days in the month prior to study entry.
• SE-03. Have received dexamethasone 6 mg once daily for more than 4 days prior to screening as part of SoC for severe/critical COVID-19
• SE-04. Had COVID-related symptoms > 14 days or hospitalized > 7 days.
• SE-05. Strong inhibitors of organic anion transporter 3 [OAT3], (e.g. probenecid) that cannot be discontinued at study entry.
• SE-06. Have received neutralizing antibodies for COVID-19, except if receiving such treatment as part of EU SolidAct part A after disease progression.
• SE-07. Have received any live vaccine within 4 weeks before screening, or intend to receive a live vaccine during the study (until day 90 (+/- 14 days)).

• SE-08. Are using or will use extracorporeal blood purification (EBP) device to remove proinflammatory cytokines from the blood such as a cytokine absorption or filtering device, for example, CytoSorb®.
• SE-09. Have diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening tests required).
• SE-10. Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product.
• SE-11. Current diagnosis of active malignancy that, in the opinion of the investigator, could constitute a risk when taking investigational product.
• SE-12. Have a history of venous thromboembolism (VTE) (deep vein thrombosis [DVT] and/or pulmonary embolism [PE]) within 12 weeks prior to randomization or have a history of recurrent (>1) VTE (DVT/PE).
• SE-13. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times ULN.
• SE-14. Subjects with estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease [MDRD]) <15 millilitre/minute/1.73 meters squared are excluded.
• SE-15. Known hypersensitivity to baricitinib or any of its excipients.
• SE-16. Are pregnant, or intend to become pregnant or breastfeed during the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified