Acute lung injury associated with COVID-19 MedDRA version: 20.1 Level: HLT Classification code 10047468 Term: Viral lower respiratory tract infections System Organ Class: 100000004855
Conditions
Interventions
Product Name: TD-0903
Pharmaceutical Form: Inhalation solution
INN or Proposed INN: TD-0903
Current Sponsor code: TD-0903
Other descriptive name: TD-0903
Concentration unit: mg/ml milligram(s)/millili
Sponsors
Theravance Biopharma Ireland Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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. 2. Willing and able to comply with study-related procedures/assessments 3. Age 18 to 80 years old 4. 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% 5. 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 2 days and = 14 days prior to hospital admission Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 72
Exclusion criteria
Exclusion criteria: 1. Subjects currently receiving invasive mechanical ventilation. 2. Presence or suspicion of active malignancy with the exception of cancer in situ (e.g., skin cancer) 3. Evidence of serious active infections other than COVID-19 4. Current diagnosis of human immunodeficiency virus, hepatitis B or C 5. In the opinion of the investigator, unlikely to survive for > 24 hours from enrollment 6. 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. 7. 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) <50 mL/min) or receiving renal replacement therapy 8. Presence of septic shock at time of enrollment 9. Hemoglobin < 80 g/L 10. Evidence of neutropenia (i.e., absolute neutrophil count < 1000 cells/µL), lymphopenia (i.e., absolute lymphocyte count < 200 cells/µL) or thrombocytopenia (i.e., platelets < 50×10^9/L) 11. Hypersensitivity to TD-0903 or its components, or to other JAK inhibitors 12. Treatment with anti-IL 6 (e.g., tocilizumab, sarilumab), anti-IL-1, anti-T cell (e.g., abatacept) antibodies, anti-IL-6R antagonists, 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 periodTreatment 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 13. 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. Monoclonal antibodies targeting B cells (eg rituximab) within 12 weeks prior to enrollment d. Tumor Necrosis Factor-alpha (TNFa) inhibitors within 4 weeks prior to enrollment 14. 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 15. Subjects with active or incompletely treated pulmonary tuberculosis, or known history of non-tuberculosis mycobacterium over past 12 months 16. Subject requires continuous oxygen supplementation for underlying cardio-respiratory history in the past 90 days 17. Body Mass Index =40 kg/m2 18. Receipt of any 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. 19. 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 The objectives are: • Evaluate the safety and tolerability of inhaled TD-0903 in subjects with COVID-19 • Assess the plasma pharmacokinetics (PK) of TD-0903 in subjects with COVID-19 • Characterize the effect of TD-0903 on reducing the acute lung injury (as measured by SaO2/FiO2 ratio) associated with COVID-19 • Explore the effect of TD-0903 on swab viral infection status, SARS-CoV-2 antibody levels, blood cytokine levels, and biomarkers of inflammation, thrombosis and lung injury Part 2 The primary objective is to characterize the efficacy of TD-0903 as measured by respiratory failure-free days (RFDs) through Day 28. ;Secondary Objective: The secondary objectives are to evaluate the effect of TD-0903 on: • Reducing the acute lung injury (as measured by SaO2/FiO2 ratio) associated with COVID-19 • Safety and tolerability • Clinical outcomes as measured by an 8-point clinical status scale • The proportion of subjects alive and respiratory failure-free on Day 28;Primary end point(s): Part 1: Endpoints (through Day 7) Safety • Change from baseline in vital signs and clinical laboratory results • Incidence and severity of treatment-emergent AEs (TEAEs) Pharmacokinetics • Plasma PK parameters on Day 1 and Day 7 Pharmacodynamics (PD) • Change from baseline in SaO2/FiO2 ratio Additional Endpoints (through Day 28) Safety • Change from baseline in vital signs, and clinical laboratory results • Incidence and severity of TEAEs Part 2 The primary endpoint is the number of RFDs from randomization through Day 28;Timepoint(s) of evaluation of this end point: Part 1: Endpoints Safety (Vital signs, clinical laboratory results, TEAEs): Day 1 through 7 PK: Day 1 pre-dose, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hours, Day 7 PD (SaO2/FiO2 ratio): Day 1 through 7 Additional Endpoints Safety (Vital signs, clinical laboratory results, TEAEs): Day 1 through 28 Part 2 The primary endpoint is: RFDs: up to Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 2: Secondary Endpoints are: • Change from baseline in SaO2/FiO2 ratio on Day 7 • Proportion of subjects in each category of the 8-point clinical status scale on Days 7, 14, 21 and 28 • Proportion of subjects alive and respiratory failure-free on Day 28;Timepoint(s) of evaluation of this end point: Part 2: • Change from baseline in SaO2/FiO2 ratio: Day 7 • Proportion of subjects in each category of the 8-point clinical status scale: Days 7, 14, 21 and 28 • Proportion of subjects alive and respiratory failure-free on Day 28 | — |
Countries
Argentina, Brazil, Finland, Moldova, Republic of, Poland, Romania, South Africa, Ukraine, United Kingdom, United States
Contacts
Public ContactRajeev Saggar
Theravance Biopharma US, Inc.
Outcome results
None listed