Clinical trial NCT04341116: Study of TJ003234 (Anti-GM-CSF Monoclonal Antibody) in Subjects With Severe Coronavirus Disease 2019 (COVID-19)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Coronavirus Disease 2019 COVID-19
Lead sponsor: I-Mab Biopharma US Limited
Sponsor class: INDUSTRY
First posted: 2020-04-10
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Subjects Alive and Free of Mechanical Ventilation Among Subjects Who Are Free of Mechanical Ventilation at Baseline
timeFrame: Day 1 through Day 30
Secondary outcomes:
measure: Percentage of Recovery by Day 14
timeFrame: Day 1 through Day 14
measure: Percentage of Subjects Recovered on Day 30
timeFrame: Day 1 through Day 30
measure: All-cause Mortality Rate by Day 30
timeFrame: Day 1 through Day 30
measure: Time to Recovery Among Subjects Alive by Day 30
timeFrame: Day 1 through Day 30
measure: Length of Hospitalization
timeFrame: Day 1 through Day 30
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas
state: Arkansas
city: Sylmar
country: United States
facility: Olive View-UCLA Medical Center
state: California
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: The GW Medical Faculty Associates
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Peoria
country: United States
facility: OSF Healthcare Saint Francis Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health
state: Indiana
city: Metairie
country: United States
facility: Medpharmics, LLC
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Albuquerque
country: United States
facility: UNM Hospitals
state: New Mexico
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
Study officials:
affiliation: I-Mab Biopharma US Limited
name: Claire Xu, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.