Overview

This Phase 2 study will evaluate the efficacy, safety, pharmacodynamics and pharmacokinetics of inhaled TD-0903 compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with confirmed COVID-19 associated acute lung injury and impaired oxygenation.

Eligibility

Inclusion Criteria:

• Willing and able to provide written informed consent on their own prior to performing study procedures. Subject assent or proxy consent as per local site procedures, may also be acceptable if both a clinician and second health professional attest that the subject understands the risks and potential benefits of the study and elects to proceed. In the event the subject loses capacity during the study, the subject consents to continued participation, except where this is not clinically indicated.
• Willing and able to comply with study-related procedures/assessments
• Age 18 to 80 years old
• Febrile ( 37.2C oral or equivalent)
• Hospitalized (or documentation of a plan to admit to the hospital if the subject is in an emergency department) and requiring supplemental oxygen to maintain saturation > 90%
• Confirmed COVID-19. If testing results are not immediately available, strong clinical suspicion of COVID-19 can be used for inclusion. Testing should still be done in these subjects. Strong clinical suspicion includes:
• At least 2 of the following:
• Fever
• Cough
• Fatigue
• Dyspnea;
• and At least 1 of the following
• Radiographic evidence of viral pneumonia
• Close contact with a patient who has previously tested positive for COVID-19
• Onset of COVID-19 -related symptoms > 2 days and </= 10 days prior to hospital admission

Exclusion Criteria:

• In the opinion of the investigator, at risk of imminent respiratory failure (i.e., on mechanical ventilation)
• Presence or suspicion of active malignancy with the exception of cancer in situ (e.g., skin cancer)
• In the opinion of the investigator, unlikely to survive for > 24 hours from enrollment
• Women who are pregnant or might be pregnant, or who are currently breast-feeding.
• Presence of significant comorbidity that, in the opinion of the investigator, predisposes the subject to mortality. Such conditions might include: a. New York Heart Association class IV Heart Failure b. Severe hepatic dysfunction c. Severe renal dysfunction or receiving renal replacement therapy
• Presence of septic shock at time of enrollment
• Hemoglobin < 80 g/L
• Platelets < 5010^9
• Hypersensitivity to TD-0903 or its components, or to other JAK inhibitors
• Treatment with anti-IL 6, anti-IL-6R antagonists, or with JAK inhibitors in the past 30 days, or plans to receive a JAK inhibitor during the study period
• Current treatment with conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs)/immunosuppressive agents including: a. Methotrexate, cyclosporine, mycophenolate, tacrolimus, penicillamine, or sulfasalazine within 2 weeks prior to enrollment b. Azathioprine or cyclophosphamide within 12 weeks prior to enrollment c. Tumor necrosis factor-alpha (TNF)) inhibitors within 12 weeks prior to enrollment
• Participating in other clinical trials involving any other experimental treatment for COVID-19, except in the context of a single-arm antiviral compassionate-use protocol
• Use of chronic oral corticosteroids for a non-COVID-19-related condition in a dose higher than prednisone 5 mg or equivalent per day
• Subjects with active or incompletely treated pulmonary tuberculosis, or known history of non-tuberculosis mycobacterium over past 12 months
• Subject requires continuous oxygen supplementation for underlying cardio-respiratory history in the past 90 days
• Body Mass Index 40 kg/cm2