TD-0903 for ALI Associated With COVID-19
Condition: Acute Lung Injury (ALI) Associated With COVID-19; Lung Inflammation Associated With COVID-19
MeSH terms: COVID-19; Pneumonia; Lung Injury; Acute Lung Injury; Inflammation
Intervention: TD-0903; Placebo
Intervention description: Study Drug to be administered by inhalation; Placebo to be administered by inhalation
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Parallel group, randomized, double-blind, placebo-controlled
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Pharmacist & Sponsor are not blinded for Part 1. Sponsor is blinded for Part 2. Pharmacist is not blinded for Part 2.
Enrollment: 235.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Acute lung injury; ALI; COVID-19; Coronavirus Disease 2019; inflammatory lung conditions; Inflammatory lung disease; ARDS; SARS-CoV-2; Pneumonia

Summary:

      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 criteria:

        Inclusion Criteria:

          -  Willing and able to provide written informed consent on their own prior to performing
             study procedures. In the U.K., 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. Outside the U.K., written informed consent may only be obtained
             from the subject or legally authorized representative. 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

          -  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%

          -  A diagnosis of symptomatic COVID-19 defined as a positive test for SARS-CoV-2 RNA
             detected by RT-PCR on a sample from the upper respiratory tract (e.g., nasopharyngeal,
             nasal, or oropharyngeal swab) collected < 72 hours prior to randomization

          -  Onset of COVID-19 -related symptoms > 2 days and </= 10 days prior to hospital
             admission

        Exclusion Criteria:

          -  Subjects currently receiving invasive mechanical ventilation

          -  Presence or suspicion of active malignancy with the exception of cancer in situ (e.g.,
             skin cancer)

          -  Evidence of serious active infection other than COVID-19

          -  Current diagnosis of human immunodeficiency virus, hepatitis B or C

          -  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.
             Subjects must agree to not donate ova or sperm through 30 days after the last dose of
             study medication

          -  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. Hepatic dysfunction (i.e., AST or ALT >3x upper
             limit of normal) c. Renal dysfunction (i.e., estimated glomerular filtration rate
             (eGFR) < 50mL/min) or receiving renal replacement therapy

          -  Presence of septic shock at time of enrollment

          -  Hemoglobin < 80 g/L

          -  Evidence of neutropenia (i.e., absolute neutrophil count < 1000 cells/uL), lymphopenia
             (i.e., absolute lymphocyte count < 200 cells/uL) or thrombocytopenia (i.e.Platelets <
             50×10^9/L)

          -  Hypersensitivity to TD-0903 or its components, or to other JAK inhibitors

          -  Treatment with anti-IL 6 (e.g., tocilizumab, sarilumab), anti-IL-6R antagonists (e.g.,
             abatacept), JAK inhibitors (e.g., baricitinib, tofacitinib) supplemental interferon
             therapy, or tyrosine kinase inhibitors (e.g., erlotinib, gefinitib) 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:

               1. Methotrexate, cyclosporine, mycophenolate, tacrolimus, penicillamine, or
                  sulfasalazine within 2 weeks prior to enrollment

               2. Azathioprine or cyclophosphamide within 12 weeks prior to enrollment

               3. Monoclonal antibodies targeting B cells (e.g., rituximab) within 12 weeks prior
                  to enrollment

               4. Tumor necrosis factor-alpha (TNFα)) inhibitors within 4 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 or convalescent plasma
             compassionate-use protocol

          -  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/m2

          -  Receipt of live vaccine (i.e., live attenuated) in the 4 weeks prior to visit 1 or
             plans to receive a live vaccine (or live attenuated) during the study period. Note:
             Use of non-live (inactivated) vaccinations is allowed for all subjects

          -  History of venous thromboembolism (VTE), deep venous thrombosis (DVT), Pulmonary
             Embolism (PE) or known hypercoagulable disorder (e.g., factor V Leiden,
             antiphospholipid antibody syndrome, protein C or S deficiency)