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

• ClinicalTrials.gov Identifier: NCT04341116
• Recruitment Status: Completed
• First Posted: April 10, 2020
• Results First Posted: May 6, 2023
• Last Update Posted: May 6, 2023
• Sponsor: I-Mab Biopharma Co. Ltd.
• Information provided by (Responsible Party): I-Mab Biopharma Co. Ltd.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Coronavirus Disease 2019 COVID-19	Drug: TJ003234; Drug: Placebo	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 149 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: April 11, 2020
• Actual Primary Completion Date: February 7, 2022
• Actual Study Completion Date: February 7, 2022

Arms and Interventions

Arm	Intervention/treatment
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
Placebo Comparator: Placebo	Drug: Placebo; patients receive a single infusion
Experimental: TJ003234 High Dose; Part 2 Phase 3 only	Drug: TJ003234; patients receive a single infusion

Outcome Measures

Primary Outcome Measures :

1. Percentage of Subjects Alive and Free of Mechanical Ventilation Among Subjects Who Are Free of Mechanical Ventilation at Baseline [ Time Frame: Day 1 through Day 30 ]

   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.

Secondary Outcome Measures :

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

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Arkansas

University of Arkansas

Little Rock, Arkansas, United States, 72205

United States, California

Olive View-UCLA Medical Center

Sylmar, California, United States, 91342

United States, District of Columbia

Georgetown University Hospital

Washington, District of Columbia, United States, 20007

The GW Medical Faculty Associates

Washington, District of Columbia, United States, 20037

United States, Florida

University of Miami

Miami, Florida, United States, 33146

United States, Illinois

OSF Healthcare Saint Francis Medical Center

Peoria, Illinois, United States, 61637

United States, Indiana

Indiana University Health

Indianapolis, Indiana, United States, 46202

United States, Louisiana

Medpharmics, LLC

Metairie, Louisiana, United States, 70006

Ochsner Medical Center

New Orleans, Louisiana, United States, 70121

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

United States, Mississippi

University of Mississippi Medical Center

Jackson, Mississippi, United States, 39216

United States, Nevada

University Medical Center of Southern Nevada

Las Vegas, Nevada, United States, 89102

United States, New Mexico

UNM Hospitals

Albuquerque, New Mexico, United States, 87106

United States, Texas

Houston Methodist Hospital

Houston, Texas, United States, 77030

Sponsors and Collaborators

I-Mab Biopharma Co. Ltd.

Investigators

• Study Director: Claire Xu, MD, PhD; I-Mab Biopharma US Limited

  Study Documents (Full-Text)

Documents provided by I-Mab Biopharma Co. Ltd.:

Study Protocol  [PDF] September 23, 2021

Statistical Analysis Plan  [PDF] April 21, 2022

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: I-Mab Biopharma Co. Ltd.
• ClinicalTrials.gov Identifier: NCT04341116
• Other Study ID Numbers: TJ003234COV201
• First Posted: April 10, 2020
• Results First Posted: May 6, 2023
• Last Update Posted: May 6, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Coronavirus Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Plonmarlimab; Anti-Inflammatory Agents; Antiviral Agents; Anti-Infective Agents