COVID-19 trials registries data warehouse

https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-000541-41/PT

Oslo University Hospital - Surgery, Inflam Diseases,Transplant

marius.troseid@medisin.uio.no

2021-05-24

Completed

RCT

Randomized

Adaptive

Blind label

multi-center

Treatment

Master Protocol Number: 2.0 dated 1 Nov 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 1 Nov 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 14 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. Note: these are based on the same criteria as in the WHO living guidelines recommending corticosteroid treatment for severe and critical COVID-19. 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. Rheumatoid arthritis, lupus, vasculitis, inflammatory bowel disease or other autoimmune disorder for which a patient is being treated with systemic immunosuppressive medication 6. Other specified cause, such as history of cancer, cancer treatment or other condition that in the opinion of the investigator could cause impaired host immunity Note: Carefully check exclusion criteria SE-01, SE-20 and SE-21 (immunosuppressive therapy), SE-22 (medical condition), SE-13 (neutropenia) and SE-14 (lymphopenia) for eligibility criteria. Immunocompromised patients should receive appropriate SoC, including anti-SARS-CoV2 monoclonal antibodies or emerging antiviral treatment, if available and indicated by current treatment guidelines at time of inclusion.

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 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.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 > 21 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)). 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 pulmonary embolism [PE]) within 12 weeks prior to randomization or have a history of recurrent (>1) VTE (DVT/PE). SE-13. Neutropenia (absolute neutrophil count <1000 cells/microliters). SE-14. Lymphopenia (absolute lymphocyte count <200 cells/microliters). SE-15. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times ULN. SE-16. Subjects with estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease [MDRD]) <15 millilitre/minute/1.73 meters squared are excluded. Note: Subjects with eGFR 15-30 are excluded unless in the opinion of the PI, the potential benefit of participation outweighs the potential risk of study participation. SE-17. Known hypersensitivity to baricitinib or any of its excipients. SE-18. Are pregnant or breastfeeding, or intend to become pregnant or breastfeed during the study. Note: Women of child bearing potential (WOCBP) can only be included based on a negative pregnancy test and WOCBP must comply with requirements regarding highly effective contraception. Refer to section 10.1 for contraception requirements. SE-19 Participation in any therapeutic clinical trials investigating immunomodulators for COVID-19

2

Oslo University Hospital

18

100

Austria;Belgium;Czech Republic;France;Germany;Greece;Hungary;Ireland;Italy;Luxembourg;Norway;Poland;Portugal;Slovakia;Spain;Turkey

Moderate/severe disease at enrollment

4: Moderate/severe disease at enrollment

100

Master Protocol Number 2.0 dated 1 Nov 2021: Part A, moderate disease: Occurrence of disease progression, defined as a progression of disease state from moderate (WHO score 4-5) to severe/critical (WHO score 6-9) or death (WHO score 10) within 14 days. Part B, severe disease: Occurrence of death within 60 days. Baricitinib specific protocol v.2.0 dated 1 Nov 2021: Occurrence of death within 60 days

Declared number of arm (3.0) differs from found arms (2.0)

Phase 3

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