Clinical trial NCT04351243: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Kinevant Sciences GmbH
Sponsor class: INDUSTRY
Collaborators: name: Roivant Sciences, Inc.
First posted: 2020-04-17
Enrollment: 227
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 exclusion criteria are detailed in the protocol.

Primary outcomes:
measure: Incidence of Mortality
timeFrame: Day 43
Secondary outcomes:
measure: Proportion of Subjects Who Are Alive and Not on Mechanical Ventilation
timeFrame: Day 29
measure: Number of Ventilator-free Days
timeFrame: Baseline to Day 29
measure: Time to Hospital Discharge
timeFrame: Baseline to Day 43
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner University Medical Center
state: Arizona
city: Phoenix
country: United States
facility: HonorHealth John C. Lincoln Medical Center
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Scottsdale Osborn Medical Center
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Scottsdale Shea Medical Center
state: Arizona
city: Tucson
country: United States
facility: Banner University Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Ronald Reagan Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: Miami Cancer institute
state: Florida
city: Atlanta
country: United States
facility: Piedmont Healthcare
state: Georgia
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Evanston
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: Metairie
country: United States
facility: East Jefferson General Hospital
state: Louisiana
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Royal Oak
country: United States
facility: Beaumont Hospital - Royal Oak
state: Michigan
city: Jamaica
country: United States
facility: Jamaica Hospital Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: New York
country: United States
facility: Mount Sinai West
state: New York
city: New York
country: United States
facility: Mount Sinai Morningside
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor Jack & Jane Hamilton Heart and Vascular Hospital
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Baylor Scott & White All Saints Medical Center
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital Affiliated with University of Texas Health Science Center at Houston, McGovern Medical School
state: Texas
city: Irving
country: United States
facility: Baylor Scott & White Medical Center
state: Texas
city: Plano
country: United States
facility: Baylor Scott & White Heart Hospital
state: Texas
city: Plano
country: United States
facility: Baylor Scott & White Medical Center
state: Texas
city: Round Rock
country: United States
facility: Baylor Scott & White Medical Center
state: Texas
city: Temple
country: United States
facility: Baylor Scott & White Medical Center
state: Texas
city: Falls Church
country: United States
facility: Inova Fairfax Medical Campus
state: Virginia
Study officials:
References:
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.