Participants |
Setting
Inpatient
Multicentre, USA
Eligibility criteria
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Inclusion criteria
Admitted to a hospital with symptoms suggestive of COVID‐19 and requires ongoing medical care
Participant(or LAR) provides informed consent prior to initiation of any study procedures
Participant(or LAR) understands and agrees to comply with planned study procedures
Male or non‐pregnant female adult ≥ 18 years of age at time of enrolment
Has laboratory‐confirmed SARS‐CoV‐2 infection as determined by PCR or other commercial or public health assay in any specimen, collected < 72 hours prior to screening; OR in sample collected >/= 72 hours but < 14 days prior to screening AND non‐improving or progressive disease suggestive of ongoing SARS‐CoV‐2 infection
Illness of any duration, and requiring, just prior to randomisation, supplemental oxygen (any flow), mechanical ventilation or ECMO (ordinal scale category 5, 6, or 7)
WOCBP must agree to either abstinence or use at least one acceptable method of contraception from the time of screening through 5 months post study intraperitoneal (IP) dosing
Agrees not to participate in another blinded clinical trial (both pharmacologic and other types of interventions) for the treatment of COVID‐19 through day 29
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Exclusion criteria
ALT or AST > 5 times ULN
Pregnancy or breastfeeding
Anticipated discharge from the hospital or transfer to another hospital that is not a study site within 72 hours of enrolment
Allergy to any study medication
Received ≥ 5 doses of remdesivir prior to screening
Received ≥ 2 doses of > 60 mg of prednisone or equivalent in the 7 days prior to screening
Received small molecule tyrosine kinase inhibitors, including Janus kinase (JAK) inhibitors (e.g. baricitinib, ibrutinib, acalabrutinib, imatinib, gefitinib), in the 4 weeks prior to screening
Received mAbs targeting cytokines (e.g. tumour necrosis factor (TNF) inhibitors, anti‐IL‐1, e.g., anakinra, canakinumab, anti‐IL‐6 (e.g., tocilizumab, sarilumab, sitlukimab), or T‐cells (e.g. abatacept) in the 4 weeks prior to screening
Received mAbs targeting B‐cells in the 3 months prior to screening
Received granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) agents (e.g. sargramostim) within 2 months prior to screening
Received other immunosuppressants in the 4 weeks prior to screening
Received any live vaccine in the 4 weeks prior to screening
Known active tuberculosis, history of HIV, Hepatitis B (HBV) or untreated hepatitis C (HCV) infection, pulmonary alveolar proteinosis (PAP)
Has active malignancy, immunodeficiency, uncontrolled opportunistic infection, or uncontrolled cirrhosis
Has a medical condition that could, in the judgment of the investigator, limit the interpretation and generalisability of trial results
Positive test for influenza virus during the current illness
Previous participation in an ACTIV‐5/BET trial
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Outcomes |
Efficacy outcomes
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All‐cause mortality
Clinical progression/improvement of symptoms: planned
Length of hospital stay: planned
Admission to ICU: not planned
Length of ICU stay: not planned
Quality of life, including fatigue: not planned
Viral clearance: not planned
Safety outcomes
Additional study outcomes
Clinical efficacy in adults hospitalised with COVID‐19 according to clinical status on an 8‐point ordinal scale
Day of recovery
Change from baseline in C‐reactive protein (CRP) concentration, d‐dimer concentration, ferritin concentration, fibrinogen concentration, troponin concentration, ALT, AST, creatinine, haemoglobin, international normalised ratio (INR), platelets, total bilirubin over time, WBC count
Clinical efficacy, as assessed by time to recovery
Discontinuation or temporary suspension of study product administration
Subject 14‐day mortality
Proportion of participants alive and without respiratory failure
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