Joint European Research on active and emerging pandemics

Phase 1

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

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-05-05
• Last Update Posted: 6 December 2021

Recruitment & Eligibility

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

Inclusion Criteria

Master Protocol Number: 2.0 dated 01 November 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 14 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. 2.0 dated 01 November 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.

In addition, the following specific inclusion criterion applies to
immunocompromised patients:
SI-01. Immunocompromised patients are eligible only if they have
elevation of 2 or more inflammatory markers above the following
cutoffs:
-Ferritin = 700 ug/l
-LDH = 400 U/L
-CRP =75 mg/dL
Immunocompromised patients are defined as the presence of at least
one of the following conditions:
1. Hematological malignancy or pre-malignancy, except acute leukemia
or history of lymphoma
2. Organ transplant recipients, except recipients of bone marrow or
solid organ transplant last 6 months, or with transplant rejection last 6
months
3. HIV positive with CD4 count < 350 cells and on stable antiretroviral
therapy
4. Primary immunodeficiency
5. Rhe

Exclusion Criteria

Master Protocol Number 2.0 dated 1 Nov 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

Baricitinib specific protocol v. 2.0 dated 1 Nov 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. Patients receiving Janus kinase (JAK) inhibitors (including
baricitinib) for any indication at screening.
• SE-20. Have received tocilizumab of sarilumab for any indication 4 weeks prior to screening.
Note: Tocilizumab as rescue therapy will be allowed in patients with
clinical progression after inclusion, see section 6.8 concomitant
medication. If tocilizumab or other immunosuppressive rescue therapy is
started, IMP should be discontinued.
• SE-21. Patients with recent changes in immunosuppressive therapy
that could interfere with the potential effect of baricitinib.
- Recipients of bone marrow transplant or solid organ transplant last 6
months, or with transplant rejection last 6 months, should not be
included.
- Organ transplant recipients receiving triple immunosuppression can
only be included if the anti-metabolite (mycophenolic acid or mTOR
inhibitor) has been temporarily discontinued per clinical practice. IMP
should be discontinued once triple immunosuppression is restarted.
• SE-22. Any medical condition that in the opinion of the investigator
poses an inacceptable risk of serious infection or aggravation of the
medical condition by participating in the trial.
Note: Patients with acute leukemia or history of lymphoma should not be
included. Cancer patients under active treatment, HIV positive
individuals with detectable HIV-RNA, or other patient group associated
with high risk of serious infection or aggravation of the medical
condition should only be included if, in the judgement of the
investigator, the potential benefit outweighs the potential risk.
• SE-03. Have received dexamethasone 6 mg daily (or alternative
regimens with equivalent of corticosteroids) 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-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.
• SE-12. Have a history of venous thromboembolism (VTE) (deep vein thrombosis [DVT] and/or pulmonar

Study & Design

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