COVID-19 trials registries data warehouse

https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001807-18/RO

Theravance Biopharma US, Inc. - Rajeev Saggar

rsaggar@theravance.com

2020-07-21

Completed

RCT

Randomized

Parallel

Blind label

multi-center

Treatment

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. Confirmed symptomatic 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 6. Onset of COVID-19-related symptoms > 2 days and < 10 days prior to hospital admission

1. Subjects requiring ventilatory support (i.e., on mechanical ventilation, non-invasive ventilation, or high-flow nasal cannula) or those subjects who, in the opinion of the investigator, are at risk of imminent respiratory failure (e.g., prolonged respiratory rate >30, signs of respiratory muscle fatigue, or paradoxical diaphragm) 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 < 500 cells/μL) or thrombocytopenia (i.e., platelets < 50×109/μL) 11. Hypersensitivity to TD-0903 or its components, or to other JAK inhibitors 12. 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 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. Tumor Necrosis Factor-alpha (TNFα) inhibitors within 12 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 compassionate-use protocol 15. Use of chronic oral corticosteroids for a non-COVID-19-related condition in a dose higher than prednisone 5 mg or equivalent per day 16. Subjects with active or incompletely treated pulmonary tuberculosis, or known history of non-tuberculosis mycobacterium over past 12 months 17. Subject requires continuous oxygen supplementation for underlying cardiorespiratory history in the past 90 days 18. Body Mass Index ≥40 kg/cm2 19. Receipt of any live vaccine in the 4 weeks prior to visit 1 or plans to receive a live vaccine during the study period 20. History of venous thromboembolism (VTE), deep venous thrombosis (DVT), Pulmonary Embolism (PE) or hypercoagulable state.

2

Theravance Biopharma Ireland Limited

18

80

Finland;Republic of Moldova;Romania;Sweden;Ukraine;United Kingdom;Ireland

Moderate disease at enrollment

3: Moderate disease at enrollment

50

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 co-primary efficacy endpoints are: • Change from baseline in SaO2/FiO2 ratio in mmHg on Day 7 • Number of VFDs from randomization to Day 28

Declared number of arm (4.0) differs from found arms (2.0)

Phase 2

[{"arm_notes": "Inhalation solution", "treatment_id": 1266, "treatment_name": "Td-0903", "treatment_type": "Kinase inhibitors", "pharmacological_treatment": "Pharmacological treatment"}, {"arm_notes": "", "treatment_id": 2187, "treatment_name": "Placebo", "treatment_type": "Placebo", "pharmacological_treatment": "Placebo"}]