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)

NCT ID: NCT04351243

Last Updated: 2021-12-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

227 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-15

Study Completion Date

2021-04-01

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.

Conditions

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COVID-19

Keywords

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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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Gimsilumab

Gimsilumab 400 mg on Day 1 Gimsilumab 200 mg on Day 8

Group Type EXPERIMENTAL

Gimsilumab

Intervention Type DRUG

Gimsilumab is a fully human monoclonal antibody (mAb).

Placebo

Normal saline on Day 1 Normal saline on Day 8

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Normal saline

Interventions

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Gimsilumab

Gimsilumab is a fully human monoclonal antibody (mAb).

Intervention Type DRUG

Placebo

Normal saline

Intervention Type DRUG

Other Intervention Names

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KIN-1901

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Roivant Sciences, Inc.

INDUSTRY

Sponsor Role collaborator

Kinevant Sciences GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Banner University Medical Center

Phoenix, Arizona, United States

Site Status

HonorHealth John C. Lincoln Medical Center

Phoenix, Arizona, United States

Site Status

HonorHealth Scottsdale Osborn Medical Center

Scottsdale, Arizona, United States

Site Status

HonorHealth

Scottsdale, Arizona, United States

Site Status

HonorHealth Scottsdale Shea Medical Center

Scottsdale, Arizona, United States

Site Status

Banner University Medical Center

Tucson, Arizona, United States

Site Status

UCLA Ronald Reagan Medical Center

Los Angeles, California, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Miami Cancer institute

Miami, Florida, United States

Site Status

Piedmont Healthcare

Atlanta, Georgia, United States

Site Status

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status

NorthShore University HealthSystem

Evanston, Illinois, United States

Site Status

East Jefferson General Hospital

Metairie, Louisiana, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Beaumont Hospital - Royal Oak

Royal Oak, Michigan, United States

Site Status

Jamaica Hospital Medical Center

Jamaica, New York, United States

Site Status

Mount Sinai Beth Israel

New York, New York, United States

Site Status

Mount Sinai West

New York, New York, United States

Site Status

Mount Sinai Morningside

New York, New York, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Baylor Jack & Jane Hamilton Heart and Vascular Hospital

Dallas, Texas, United States

Site Status

Baylor University Medical Center

Dallas, Texas, United States

Site Status

Baylor Scott & White All Saints Medical Center

Fort Worth, Texas, United States

Site Status

Memorial Hermann Hospital Affiliated with University of Texas Health Science Center at Houston, McGovern Medical School

Houston, Texas, United States

Site Status

Baylor Scott & White Medical Center

Irving, Texas, United States

Site Status

Baylor Scott & White Heart Hospital

Plano, Texas, United States

Site Status

Baylor Scott & White Medical Center

Plano, Texas, United States

Site Status

Baylor Scott & White Medical Center

Round Rock, Texas, United States

Site Status

Baylor Scott & White Medical Center

Temple, Texas, United States

Site Status

Inova Fairfax Medical Campus

Falls Church, Virginia, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 35290169 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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KIN-1901-2001

Identifier Type: -

Identifier Source: org_study_id