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

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)

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.

Study Overview

• Status: Completed
• Conditions: Coronavirus Disease 2019 COVID-19
• Intervention / Treatment: Drug: TJ003234; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 149
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas
  • California
    • Sylmar, California, United States, 91342
      • Olive View-UCLA Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
    • Washington, District of Columbia, United States, 20037
      • The GW Medical Faculty Associates
  • Florida
    • Miami, Florida, United States, 33146
      • University of Miami
  • Illinois
    • Peoria, Illinois, United States, 61637
      • OSF HealthCare Saint Francis Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • MedPharmics, LLC
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • UNM Hospitals
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; patients receive a single infusion
Experimental: TJ003234 Medium Dose	Drug: TJ003234; patients receive a single infusion
Experimental: TJ003234 Low Dose; Part 1 only	Drug: TJ003234; patients receive a single infusion
Experimental: TJ003234 High Dose; Part 2 Phase 3 only	Drug: TJ003234; patients receive a single infusion

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: I-Mab Biopharma Co. Ltd.
• Investigators: Study Director: Claire Xu, MD, PhD, I-Mab Biopharma US Limited

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2020
• Primary Completion (Actual): February 7, 2022
• Study Completion (Actual): February 7, 2022

Study Registration Dates

• First Submitted: April 4, 2020
• First Submitted That Met QC Criteria: April 9, 2020
• First Posted (Actual): April 10, 2020

Study Record Updates

• Last Update Posted (Estimate): May 4, 2023
• Last Update Submitted That Met QC Criteria: May 3, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Anti-Infective Agents; Antiviral Agents; Anti-Inflammatory Agents; Plonmarlimab
• Other Study ID Numbers: TJ003234COV201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No