Joint European Research on active and emerging pandemics

Phase 1

• Conditions: SARS-CoV infection; MedDRA version: 21.1Level: LLTClassification code 10037373Term: Pulmonary disorderSystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2021-000541-41-ES
• Lead Sponsor: Oslo University Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-11
• Last Update Posted: 12 July 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.
o Note: A washout period is required prior to screening
• 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.
o Note: If hospitalized early in the disease and then progressing after >7 days of hospitalization, the patient could still be included if COVID-related symptoms had a duration < 14 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)).
o Note: Use of non-live (inactivated) vaccinations, including COVID-19 vaccinations, is allowed for all participants.
• 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.
o Note: Immunocompromised patients, patients with a chronic medical condition, or those taking a medication that cannot be discontinued at enrolment, who, in the judgment of the investigator, are at increased risk for serious infections or other safety concerns should be excluded. However, well treated HIV infection with normal CD4+ T cell count and undetectable HIV-RNA is not an exclusion criterion per se.
• SE-11. Current diagnosis of active malignancy that, in the opinion of the investigator, could constitute a risk when taking investigational product.
o Note: although this risk is established from long term use of baricitinib

Study & Design

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