Study of TJ003234 (Anti-GM-CSF Monoclonal Antibody) in Subjects With Severe Coronavirus Disease 2019 (COVID-19)

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multi-center trial to evaluate the safety and efficacy of TJ003234 administered as an intravenous (IV) infusion in subjects with severe COVID-19 under supportive care, and to assess the effect of TJ003234 on the levels of cytokines.

Official Title
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A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of TJ003234 in Subjects With Severe Coronavirus Disease 2019 (COVID-19)

Conditions
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Coronavirus Disease 2019 COVID-19

Intervention / Treatment
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* Drug: TJ003234
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18 years or older (including 18 years); male or female Laboratory-confirmed SARS-CoV-2 or COVID-19 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay. Bilateral lung infection confirmed by imaging. Severe disease that meets one of the following conditions: (i) At rest, finger blood oxygen saturation ≤ 93% or PaO2/FiO2 ≤ 300 mmHg; (ii) Requiring non-invasive or invasive mechanical ventilation; OR (iii) Requiring high flow oxygen ≥ 15L/min Hospitalized for no more than 5 calendar days at the time of screening Exclusion Criteria: Any previous and/or current clinically significant disease or condition that has not been stable within 3 months prior to enrollment, or acute illness, planned medical/ surgical procedure, or any trauma that occurred within 2 weeks prior to enrollment. Chronic obstructive pulmonary disease (COPD) patients requiring inhaled corticosteroid, long-acting beta-adrenergic agonists, long-acting anticholinergics, or long-term oxygen therapy (Part 1 only). Pulmonary interstitial disease, pulmonary alveolar proteinosis, and pulmonary granulomatosis. Cardiovascular event in the 3 months prior to study drug administration: acute myocardial infarction or unstable angina pectoris, severe arrhythmia (multiple sources of frequent ventricular premature beat, ventricular tachycardia and ventricular fibrillation); New York Heart Association Classification (NYHA): Class III-Class IV. Blood system disorders or routine blood analysis test abnormalities: Hemoglobin < 8 g/dL; Absolute neutrophil count (ANC) <1500 × 109/L; Platelets < 50 × 109/L. Dependence on glucocorticoid treatment equivalent to methylprednisolone 2 mg/kg/ day or more or long-term use of anti-rejection or immunomodulatory drugs. Subjects that have been on invasive mechanical ventilation for ≥120 hours at the time of dosing Subjects that require ECMO. Pregnant or breastfeeding females.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TJ003234 Medium Dose<br> | Drug: TJ003234<br>* patients receive a single infusion<br>|
| Experimental: TJ003234 Low Dose<br>Part 1 only | Drug: TJ003234<br>* patients receive a single infusion<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* patients receive a single infusion<br>|
| Experimental: TJ003234 High Dose<br>Part 2 Phase 3 only | Drug: TJ003234<br>* patients receive a single infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Alive and Free of Mechanical Ventilation Among Subjects Who Are Free of Mechanical Ventilation at Baseline | Free of mechanical ventilation was defined as proportion of subjects who scores 1 to 5 in the following 8-category ordinal scale. 8, death; 7, ventilation in addition to extracorporeal membrane oxygen (ECMO), continuous renal replacement therapy (CRRT) or pressors; 6, intubation and mechanical ventilation; 5, non-invasive mechanical ventilation (NIV) or high-flow oxygen; 4, hospitalization with oxygen by mask or nasal prongs; 3. Hospitalization without oxygen supplementation; 2, limitation of activities, discharge from hospital; and 1, no limitation of activities, discharge from hospital. | Day 1 through Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Recovery by Day 14 | Sustained recovery in clinical status was defined as patients who have hospitalization without oxygen supplement or discharge from hospital. | Day 1 through Day 14 | 
| Percentage of Subjects Recovered on Day 30 | Sustained recovery in clinical status was defined as patients who have hospitalization without oxygen supplement or discharge from hospital. | Day 1 through Day 30 | 
| All-cause Mortality Rate by Day 30 | The percentage of subjects who deceased by any cause. | Day 1 through Day 30 | 
| Time to Recovery Among Subjects Alive by Day 30 | Time to sustained recovery | Day 1 through Day 30 | 
| Length of Hospitalization | Duration of hospitalization | Day 1 through Day 30 |