Coronavirus Disease 2019 COVID-19
Conditions
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.
Interventions
DRUGTJ003234
patients receive a single infusion
DRUGPlacebo
patients receive a single infusion
Sponsors
I-Mab Biopharma US Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Alive and Free of Mechanical Ventilation Among Subjects Who Are Free of Mechanical Ventilation at Baseline | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Recovery by Day 14 | Day 1 through Day 14 | Sustained recovery in clinical status was defined as patients who have hospitalization without oxygen supplement or discharge from hospital. |
| Percentage of Subjects Recovered on Day 30 | Day 1 through Day 30 | Sustained recovery in clinical status was defined as patients who have hospitalization without oxygen supplement or discharge from hospital. |
| All-cause Mortality Rate by Day 30 | Day 1 through Day 30 | The percentage of subjects who deceased by any cause. |
| Time to Recovery Among Subjects Alive by Day 30 | Day 1 through Day 30 | Time to sustained recovery |
| Length of Hospitalization | Day 1 through Day 30 | Duration of hospitalization |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TJ003234 3mg/kg (Part 1) subjects treated by 3mg/kg of TJ003234 | 8 |
| TJ003234 6mg/kg (Part 1) subjects treated by 6mg/kg of TJ003234 in Part 1 | 8 |
| Placebo (Part 1) subjects treated by placebo in Part 1 | 8 |
| TJ003234 6mg/kg (Part 2) subjects treated by 6mg/kg of TJ003234 in Part 2 | 77 |
| TJ003234 10mg/kg (Part 2) subjects treated by 10 mg/kg of TJ003234 in Part 2 | 6 |
| Placebo (Part 2) subjects treated by placebo in Part 2 | 42 |
| Total | 149 |
Baseline characteristics
| Characteristic | TJ003234 3mg/kg (Part 1) | TJ003234 6mg/kg (Part 1) | Placebo (Part 1) | TJ003234 6mg/kg (Part 2) | TJ003234 10mg/kg (Part 2) | Placebo (Part 2) | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 51.9 years | 58.4 years | 58 years | 55.6 years | 57.2 years | 56.4 years | 56 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 33 Participants | 2 Participants | 16 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 7 Participants | 7 Participants | 44 Participants | 4 Participants | 26 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 168.8 cm | 166.8 cm | 173.3 cm | 167.1 cm | 171.0 cm | 168.3 cm | 168.65 cm |
| Mechanical Ventilation No | 3 Participants | 1 Participants | 2 Participants | 67 Participants | 6 Participants | 36 Participants | 115 Participants |
| Mechanical Ventilation Unknown | 2 Participants | 4 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 9 Participants |
| Mechanical Ventilation Yes | 3 Participants | 3 Participants | 3 Participants | 10 Participants | 0 Participants | 6 Participants | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 3 Participants | 23 Participants | 3 Participants | 10 Participants | 46 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 11 Participants | 0 Participants | 6 Participants | 17 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 5 Participants | 39 Participants | 3 Participants | 21 Participants | 77 Participants |
| Region of Enrollment United States | 8 participants | 8 participants | 8 participants | 77 participants | 6 participants | 42 participants | 149 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 4 Participants | 49 Participants | 4 Participants | 24 Participants | 88 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 4 Participants | 28 Participants | 2 Participants | 18 Participants | 61 Participants |
| Weight | 101.4 kg | 88.0 kg | 108.9 kg | 97.2 kg | 98.1 kg | 97.1 kg | 98.3 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 8 | 1 / 8 | 2 / 8 | 11 / 77 | 1 / 6 | 10 / 42 |
| other Total, other adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 77 | 0 / 6 | 0 / 42 |
| serious Total, serious adverse events | 2 / 8 | 4 / 8 | 2 / 8 | 22 / 77 | 1 / 6 | 16 / 42 |
Outcome results
Primary
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.
Time frame: Day 1 through Day 30
Population: All subjects randomized to treatment who were mechanical ventilation free at baseline was collected only for Part 2 arms/groups. Data was not collected from the Part 1 Arms/Groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TJ003234 6mg/kg (Part 2) | Percentage of Subjects Alive and Free of Mechanical Ventilation Among Subjects Who Are Free of Mechanical Ventilation at Baseline | 56 Participants |
| TJ0032034 10mg/kg (Part 2) | Percentage of Subjects Alive and Free of Mechanical Ventilation Among Subjects Who Are Free of Mechanical Ventilation at Baseline | 5 Participants |
| Placebo (Part 2) | Percentage of Subjects Alive and Free of Mechanical Ventilation Among Subjects Who Are Free of Mechanical Ventilation at Baseline | 27 Participants |
p-value: 0.2895% CI: [-6.5, 27]Fisher Exact
Secondary
All-cause Mortality Rate by Day 30
The percentage of subjects who deceased by any cause.
Time frame: Day 1 through Day 30
Population: All subjects randomized was collected only for Part 2 arms/groups. Data was not collected from the Part 1 Arms/Groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TJ003234 6mg/kg (Part 2) | All-cause Mortality Rate by Day 30 | 7 Participants |
| TJ0032034 10mg/kg (Part 2) | All-cause Mortality Rate by Day 30 | 1 Participants |
| Placebo (Part 2) | All-cause Mortality Rate by Day 30 | 9 Participants |
Secondary
Length of Hospitalization
Duration of hospitalization
Time frame: Day 1 through Day 30
Population: All subjects without mechanical ventilation- Part 2. Part 1 is designed as a randomized, double-blind, placebo-controlled, 3-arm, parallel-group study to evaluate the safety of plonmarlimab in subjects with severe COVID-19. So, no available efficacy data for this part.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TJ003234 6mg/kg (Part 2) | Length of Hospitalization | 10 days |
| TJ0032034 10mg/kg (Part 2) | Length of Hospitalization | 9.5 days |
| Placebo (Part 2) | Length of Hospitalization | 11 days |
Secondary
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.
Time frame: Day 1 through Day 14
Population: All subjects randomized was collected only for Part 2 arms/groups. Data was not collected from the Part 1 Arms/Groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TJ003234 6mg/kg (Part 2) | Percentage of Recovery by Day 14 | 47 Participants |
| TJ0032034 10mg/kg (Part 2) | Percentage of Recovery by Day 14 | 5 Participants |
| Placebo (Part 2) | Percentage of Recovery by Day 14 | 20 Participants |
Secondary
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.
Time frame: Day 1 through Day 30
Population: All subjects randomized was collected only for Part 2 arms/groups. Data was not collected from the Part 1 Arms/Groups.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TJ003234 6mg/kg (Part 2) | Percentage of Subjects Recovered on Day 30 | 56 Participants |
| TJ0032034 10mg/kg (Part 2) | Percentage of Subjects Recovered on Day 30 | 5 Participants |
| Placebo (Part 2) | Percentage of Subjects Recovered on Day 30 | 27 Participants |
Secondary
Time to Recovery Among Subjects Alive by Day 30
Time to sustained recovery
Time frame: Day 1 through Day 30
Population: All subjects randomized without mechanical ventilation Part 2. Part 1 is designed as a randomized, double-blind, placebo-controlled, 3-arm, parallel-group study to evaluate the safety of plonmarlimab in subjects with severe COVID-19. So, no available efficacy data for this part.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TJ003234 6mg/kg (Part 2) | Time to Recovery Among Subjects Alive by Day 30 | 8 days |
| TJ0032034 10mg/kg (Part 2) | Time to Recovery Among Subjects Alive by Day 30 | 6.5 days |
| Placebo (Part 2) | Time to Recovery Among Subjects Alive by Day 30 | 10 days |