Back to resultsA Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE)
Primary Purpose
COVID-19
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gimsilumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring Granulocyte macrophage-colony stimulating factor (GM-CSF), Immunomodulator, Cytokine storm, COVID-19, Coronavirus, Severe Acute Respiratory Syndrome (SARS), Lung Injury, Monoclonal antibody
Eligibility Criteria
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.
Sites / Locations
- Banner University Medical Center
- HonorHealth John C. Lincoln Medical Center
- HonorHealth Scottsdale Osborn Medical Center
- HonorHealth
- HonorHealth Scottsdale Shea Medical Center
- Banner University Medical Center
- UCLA Ronald Reagan Medical Center
- University of Florida
- Miami Cancer institute
- Piedmont Healthcare
- Emory University School of Medicine
- NorthShore University HealthSystem
- East Jefferson General Hospital
- Brigham and Women's Hospital
- Beaumont Hospital - Royal Oak
- Jamaica Hospital Medical Center
- Mount Sinai Beth Israel
- Mount Sinai West
- Mount Sinai Morningside
- Icahn School of Medicine at Mount Sinai
- University Hospitals Cleveland Medical Center
- Temple University Hospital
- Vanderbilt University Medical Center
- Baylor Jack & Jane Hamilton Heart and Vascular Hospital
- Baylor University Medical Center
- Baylor Scott & White All Saints Medical Center
- Memorial Hermann Hospital Affiliated with University of Texas Health Science Center at Houston, McGovern Medical School
- Baylor Scott & White Medical Center
- Baylor Scott & White Heart Hospital
- Baylor Scott & White Medical Center
- Baylor Scott & White Medical Center
- Baylor Scott & White Medical Center
- Inova Fairfax Medical Campus
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Gimsilumab
Placebo
Arm Description
Gimsilumab 400 mg on Day 1 Gimsilumab 200 mg on Day 8
Normal saline on Day 1 Normal saline on Day 8
Outcomes
Primary Outcome Measures
Incidence of Mortality
"Incidence" is defined as the percent of subjects that died by Day 43
Secondary Outcome Measures
Proportion of Subjects Who Are Alive and Not on Mechanical Ventilation
Number of Ventilator-free Days
Subjects who die will be assigned "0" ventilator-free days
Time to Hospital Discharge
Full Information
NCT ID
NCT04351243
First Posted
April 15, 2020
Last Updated
December 10, 2021
Sponsor
Kinevant Sciences GmbH
Collaborators
Roivant Sciences, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04351243
Brief Title
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)
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
April 15, 2020 (Actual)
Primary Completion Date
December 1, 2020 (Actual)
Study Completion Date
April 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kinevant Sciences GmbH
Collaborators
Roivant Sciences, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Granulocyte macrophage-colony stimulating factor (GM-CSF), Immunomodulator, Cytokine storm, COVID-19, Coronavirus, Severe Acute Respiratory Syndrome (SARS), Lung Injury, Monoclonal antibody
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
227 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Gimsilumab
Arm Type
Experimental
Arm Description
Gimsilumab 400 mg on Day 1 Gimsilumab 200 mg on Day 8
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Normal saline on Day 1 Normal saline on Day 8
Intervention Type
Drug
Intervention Name(s)
Gimsilumab
Other Intervention Name(s)
KIN-1901
Intervention Description
Gimsilumab is a fully human monoclonal antibody (mAb).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Normal saline
Primary Outcome Measure Information:
Title
Incidence of Mortality
Description
"Incidence" is defined as the percent of subjects that died by Day 43
Time Frame
Day 43
Secondary Outcome Measure Information:
Title
Proportion of Subjects Who Are Alive and Not on Mechanical Ventilation
Time Frame
Day 29
Title
Number of Ventilator-free Days
Description
Subjects who die will be assigned "0" ventilator-free days
Time Frame
Baseline to Day 29
Title
Time to Hospital Discharge
Time Frame
Baseline to Day 43
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Banner University Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
HonorHealth John C. Lincoln Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85020
Country
United States
Facility Name
HonorHealth Scottsdale Osborn Medical Center
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85251
Country
United States
Facility Name
HonorHealth
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
HonorHealth Scottsdale Shea Medical Center
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85260
Country
United States
Facility Name
Banner University Medical Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Facility Name
UCLA Ronald Reagan Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Miami Cancer institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Piedmont Healthcare
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
NorthShore University HealthSystem
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
East Jefferson General Hospital
City
Metairie
State/Province
Louisiana
ZIP/Postal Code
70006
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beaumont Hospital - Royal Oak
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Jamaica Hospital Medical Center
City
Jamaica
State/Province
New York
ZIP/Postal Code
11418
Country
United States
Facility Name
Mount Sinai Beth Israel
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Mount Sinai West
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Facility Name
Mount Sinai Morningside
City
New York
State/Province
New York
ZIP/Postal Code
10025
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Temple University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Baylor Jack & Jane Hamilton Heart and Vascular Hospital
City
Dallas
State/Province
Texas
ZIP/Postal Code
75226
Country
United States
Facility Name
Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Baylor Scott & White All Saints Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
75061
Country
United States
Facility Name
Memorial Hermann Hospital Affiliated with University of Texas Health Science Center at Houston, McGovern Medical School
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Baylor Scott & White Medical Center
City
Irving
State/Province
Texas
ZIP/Postal Code
75061
Country
United States
Facility Name
Baylor Scott & White Heart Hospital
City
Plano
State/Province
Texas
ZIP/Postal Code
75093
Country
United States
Facility Name
Baylor Scott & White Medical Center
City
Plano
State/Province
Texas
ZIP/Postal Code
75093
Country
United States
Facility Name
Baylor Scott & White Medical Center
City
Round Rock
State/Province
Texas
ZIP/Postal Code
78665
Country
United States
Facility Name
Baylor Scott & White Medical Center
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Inova Fairfax Medical Campus
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35290169
Citation
Criner GJ, Lang FM, Gottlieb RL, Mathews KS, Wang TS, Rice TW, Madduri D, Bellam S, Jeanfreau R, Case AH, Glassberg MK, Lyon GM, Ahmad K, Mendelson R, DiMaio JM, Tran MP, Spak CW, Abbasi JA, Davis SG, Ghamande S, Shen S, Sherman L, Lowry S. Anti-Granulocyte-Macrophage Colony-Stimulating Factor Monoclonal Antibody Gimsilumab for COVID-19 Pneumonia: A Randomized, Double-Blind, Placebo-controlled Trial. Am J Respir Crit Care Med. 2022 Jun 1;205(11):1290-1299. doi: 10.1164/rccm.202108-1859OC. Erratum In: Am J Respir Crit Care Med. 2022 Sep 15;206(6):801.
Results Reference
derived
Learn more about this trial
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)
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