COVID-19
Conditions
Keywords
Granulocyte macrophage-colony stimulating factor (GM-CSF), Immunomodulator, Cytokine storm, COVID-19, Coronavirus, Severe Acute Respiratory Syndrome (SARS), Lung Injury, Monoclonal antibody
Brief summary
Study KIN-1901-2001 is a multi-center, adaptive, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of gimsilumab in subjects with lung injury or acute respiratory distress syndrome (ARDS) secondary to COVID-19.
Detailed description
Gimsilumab is a monoclonal antibody against granulocyte macrophage-colony stimulating factor (GM-CSF), which is a myeloid cell growth factor and pro- inflammatory cytokine. Late stages of COVID-19 can be marked by a cytokine storm and the overactivation of inflammatory myeloid cells that infiltrate and damage tissue, such as the lungs. Inhibition of GM-CSF may be able to reverse this pathology. The anti-GM-CSF mechanism is distinct from antiviral therapeutic mechanisms and may provide synergistic effects when used in combination. Study KIN-1901-2001 will consist of a 2-week treatment period (last dose Day 8, if administered) and a 22-week follow-up period, for a total study duration of 24 weeks for each subject. A total of 270 subjects (135 subjects per arm) who have a confirmed diagnosis of COVID-19 with clinical evidence of acute lung injury or ARDS will be entered into the trial. Subjects will receive a 400 mg dose of gimsilumab on Day 1 and a 200 mg dose of gimsilumab on Day 8, or matching placebo (saline solution) on Day 1 and on Day 8. The Day 8 dose will be omitted if the subject is discharged from the hospital prior to the dose or is no longer in need of supplemental oxygen or ventilatory support for \>48 hours. The primary objective of Study KIN-1901-2001 is to evaluate the impact of IV treatment with gimsilumab on mortality in subjects with lung injury or ARDS secondary to COVID-19.
Interventions
DRUGGimsilumab
Gimsilumab is a fully human monoclonal antibody (mAb).
DRUGPlacebo
Normal saline
Sponsors
Roivant Sciences, Inc.
Kinevant Sciences GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or non-pregnant female age ≥18 years, inclusive 2. Subject (or legally authorized representative) is able and willing to provide written informed consent, which includes compliance with study requirements and restrictions listed in the consent form 3. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other approved clinical testing prior to randomization 4. Radiographic evidence of bilateral infiltrates 5. Subject requires high-flow oxygen or meets clinical classification for ARDS 6. Elevated serum CRP or ferritin 7. Subjects who have been treated with convalescent plasma (CP) prior to enrollment are eligible if the subject continues to meet all inclusion criteria at screening 8. The use of investigational anti-viral treatment (e.g., remdesivir) is allowed if the subject continues to meet all inclusion criteria at screening Additional inclusion criteria are detailed in the protocol
Exclusion criteria
1. Evidence of life-threatening dysrhythmia or cardiac arrest on presentation 2. Intubated \>72 hours 3. Absolute neutrophil count \< 1,000 per mm3 4. Platelet count \< 50,000 per mm3 5. AST or ALT \> 5X upper limit of normal 6. eGFR \<30 mL/min/1.73m2 or requiring hemofiltration or dialysis 7. History of known anti-GM-CSF autoantibodies or pulmonary alveolar proteinosis 8. Severe chronic respiratory disease (e.g., COPD, PAH, IPF, ILD) requiring supplemental oxygen therapy or mechanical ventilation pre-hospitalization (e.g., prior to COVID-19 diagnosis) 9. Use of any immunomodulatory biologic, cell therapy, or small molecule JAK inhibitor within past 7 days or 5 half lives or planned use of any of these agents unless approved by medical monitor 10. Chronic (\>4 weeks) use of corticosteroids \>10mg/day of prednisone or equivalent 11. Known or suspected active and untreated TB, HIV, hepatitis B or C infection Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Mortality | Day 43 | Incidence is defined as the percent of subjects that died by Day 43 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Who Are Alive and Not on Mechanical Ventilation | Day 29 | — |
| Number of Ventilator-free Days | Baseline to Day 29 | Subjects who die will be assigned 0 ventilator-free days |
| Time to Hospital Discharge | Baseline to Day 43 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gimsilumab Gimsilumab 400 mg on Day 1 Gimsilumab 200 mg on Day 8
Gimsilumab: Gimsilumab is a fully human monoclonal antibody (mAb). | 113 |
| Placebo Normal saline on Day 1 Normal saline on Day 8
Placebo: Normal saline | 112 |
| Total | 225 |
Baseline characteristics
| Characteristic | Placebo | Total | Gimsilumab |
|---|---|---|---|
| Age, Continuous | 60.4 years STANDARD_DEVIATION 14.27 | 60.2 years STANDARD_DEVIATION 14.44 | 59.9 years STANDARD_DEVIATION 14.66 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 42 Participants | 101 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 70 Participants | 124 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 29 Participants | 45 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 23 Participants | 53 Participants | 30 Participants |
| Race (NIH/OMB) White | 52 Participants | 113 Participants | 61 Participants |
| Sex: Female, Male Female | 31 Participants | 71 Participants | 40 Participants |
| Sex: Female, Male Male | 81 Participants | 154 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 32 / 113 | 31 / 112 |
| other Total, other adverse events | 84 / 113 | 77 / 112 |
| serious Total, serious adverse events | 47 / 113 | 45 / 112 |
Outcome results
Primary
Incidence of Mortality
Incidence is defined as the percent of subjects that died by Day 43
Time frame: Day 43
Population: Intent-to-Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gimsilumab | Incidence of Mortality | 32 Participants |
| Placebo | Incidence of Mortality | 26 Participants |
p-value: 0.188595% CI: [-0.06, 0.17]Mantel Haenszel
Secondary
Number of Ventilator-free Days
Subjects who die will be assigned 0 ventilator-free days
Time frame: Baseline to Day 29
Population: Intent-to-Treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gimsilumab | Number of Ventilator-free Days | 29.0 Days |
| Placebo | Number of Ventilator-free Days | 29.0 Days |
Secondary
Proportion of Subjects Who Are Alive and Not on Mechanical Ventilation
Time frame: Day 29
Population: Intent-to-Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gimsilumab | Proportion of Subjects Who Are Alive and Not on Mechanical Ventilation | 80 Participants |
| Placebo | Proportion of Subjects Who Are Alive and Not on Mechanical Ventilation | 78 Participants |
Secondary
Time to Hospital Discharge
Time frame: Baseline to Day 43
Population: Intent-to-Treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gimsilumab | Time to Hospital Discharge | 13.0 Days |
| Placebo | Time to Hospital Discharge | 15.0 Days |