A Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE)

Study Overview
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Brief Summary
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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
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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.

Official Title
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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 Secondary to COVID-19 (BREATHE)

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Gimsilumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant female age ≥18 years, inclusive 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 Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other approved clinical testing prior to randomization Radiographic evidence of bilateral infiltrates Subject requires high-flow oxygen or meets clinical classification for ARDS Elevated serum CRP or ferritin 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 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: Evidence of life-threatening dysrhythmia or cardiac arrest on presentation Intubated >72 hours Absolute neutrophil count < 1,000 per mm3 Platelet count < 50,000 per mm3 AST or ALT > 5X upper limit of normal eGFR <30 mL/min/1.73m2 or requiring hemofiltration or dialysis History of known anti-GM-CSF autoantibodies or pulmonary alveolar proteinosis 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) 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 Chronic (>4 weeks) use of corticosteroids >10mg/day of prednisone or equivalent Known or suspected active and untreated TB, HIV, hepatitis B or C infection Additional exclusion criteria are detailed in the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gimsilumab<br>Gimsilumab 400 mg on Day 1 Gimsilumab 200 mg on Day 8 | Drug: Gimsilumab<br>* Gimsilumab is a fully human monoclonal antibody (mAb).<br>* Other names: KIN-1901;|
| Placebo Comparator: Placebo<br>Normal saline on Day 1 Normal saline on Day 8 | Drug: Placebo<br>* Normal saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Mortality | Incidence is defined as the percent of subjects that died by Day 43 | Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Who Are Alive and Not on Mechanical Ventilation |  | Day 29 | 
| Number of Ventilator-free Days | Subjects who die will be assigned 0 ventilator-free days | Baseline to Day 29 | 
| Time to Hospital Discharge |  | Baseline to Day 43 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Granulocyte macrophage-colony stimulating factor (GM-CSF), Immunomodulator, Cytokine storm, COVID-19, Coronavirus, Severe Acute Respiratory Syndrome (SARS), Lung Injury, Monoclonal antibody