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)

COVID-19 Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04351243
• Other study ID #: KIN-1901-2001
• Status: Completed
• Phase: Phase 2
• Start date: April 15, 2020
• Est. completion date: April 1, 2021

Study information

• Verified date: December 2021
• Source: Kinevant Sciences GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 227
• Est. completion date: April 1, 2021
• Est. primary completion date: December 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lung Injury
• COVID-19
• Lung Injury
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn

Intervention

Drug:
• Gimsilumab
Gimsilumab is a fully human monoclonal antibody (mAb).
• Placebo
Normal saline

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Piedmont Healthcare	Atlanta	Georgia
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Baylor Jack & Jane Hamilton Heart and Vascular Hospital	Dallas	Texas
United States	Baylor University Medical Center	Dallas	Texas
United States	NorthShore University HealthSystem	Evanston	Illinois
United States	Inova Fairfax Medical Campus	Falls Church	Virginia
United States	Baylor Scott & White All Saints Medical Center	Fort Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	Memorial Hermann Hospital Affiliated with University of Texas Health Science Center at Houston, McGovern Medical School	Houston	Texas
United States	Baylor Scott & White Medical Center	Irving	Texas
United States	Jamaica Hospital Medical Center	Jamaica	New York
United States	UCLA Ronald Reagan Medical Center	Los Angeles	California
United States	East Jefferson General Hospital	Metairie	Louisiana
United States	Miami Cancer institute	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Mount Sinai Beth Israel	New York	New York
United States	Mount Sinai Morningside	New York	New York
United States	Mount Sinai West	New York	New York
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Banner University Medical Center	Phoenix	Arizona
United States	HonorHealth John C. Lincoln Medical Center	Phoenix	Arizona
United States	Baylor Scott & White Heart Hospital	Plano	Texas
United States	Baylor Scott & White Medical Center	Plano	Texas
United States	Baylor Scott & White Medical Center	Round Rock	Texas
United States	Beaumont Hospital - Royal Oak	Royal Oak	Michigan
United States	HonorHealth	Scottsdale	Arizona
United States	HonorHealth Scottsdale Osborn Medical Center	Scottsdale	Arizona
United States	HonorHealth Scottsdale Shea Medical Center	Scottsdale	Arizona
United States	Baylor Scott & White Medical Center	Temple	Texas
United States	Banner University Medical Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Kinevant Sciences GmbH	Roivant Sciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Mortality	"Incidence" is defined as the percent of subjects that died by Day 43	Day 43
Secondary	Proportion of Subjects Who Are Alive and Not on Mechanical Ventilation		Day 29
Secondary	Number of Ventilator-free Days	Subjects who die will be assigned "0" ventilator-free days	Baseline to Day 29
Secondary	Time to Hospital Discharge		Baseline to Day 43