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)
- Registration Number
- NCT04351243
- Lead Sponsor
- Kinevant Sciences GmbH
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 227
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Normal saline on Day 1 Normal saline on Day 8 Gimsilumab Gimsilumab Gimsilumab 400 mg on Day 1 Gimsilumab 200 mg on Day 8
- Primary Outcome Measures
Name Time Method Incidence of Mortality Day 43 "Incidence" is defined as the percent of subjects that died by Day 43
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (29)
Banner University Medical Center
🇺🇸Tucson, Arizona, United States
HonorHealth
🇺🇸Scottsdale, Arizona, United States
HonorHealth Scottsdale Shea Medical Center
🇺🇸Scottsdale, Arizona, United States
UCLA Ronald Reagan Medical Center
🇺🇸Los Angeles, California, United States
Piedmont Healthcare
🇺🇸Atlanta, Georgia, United States
Beaumont Hospital - Royal Oak
🇺🇸Royal Oak, Michigan, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
NorthShore University HealthSystem
🇺🇸Evanston, Illinois, United States
Baylor Scott & White All Saints Medical Center
🇺🇸Fort Worth, Texas, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Baylor Scott & White Heart Hospital
🇺🇸Plano, Texas, United States
HonorHealth John C. Lincoln Medical Center
🇺🇸Phoenix, Arizona, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Jamaica Hospital Medical Center
🇺🇸Jamaica, New York, United States
University of Florida
🇺🇸Gainesville, Florida, United States
East Jefferson General Hospital
🇺🇸Metairie, Louisiana, United States
Miami Cancer institute
🇺🇸Miami, Florida, United States
Inova Fairfax Medical Campus
🇺🇸Falls Church, Virginia, United States
Mount Sinai West
🇺🇸New York, New York, United States
HonorHealth Scottsdale Osborn Medical Center
🇺🇸Scottsdale, Arizona, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Baylor Scott & White Medical Center
🇺🇸Temple, Texas, United States
Mount Sinai Beth Israel
🇺🇸New York, New York, United States
Mount Sinai Morningside
🇺🇸New York, New York, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Baylor Jack & Jane Hamilton Heart and Vascular Hospital
🇺🇸Dallas, Texas, United States
Memorial Hermann Hospital Affiliated with University of Texas Health Science Center at Houston, McGovern Medical School
🇺🇸Houston, Texas, United States