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)

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 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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Placebo; Drug: Gimsilumab

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.

• Study Type: Interventional
• Enrollment (Actual): 227
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center
    • Phoenix, Arizona, United States, 85020
      • HonorHealth John C. Lincoln Medical Center
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth
    • Scottsdale, Arizona, United States, 85251
      • HonorHealth Scottsdale Osborn Medical Center
    • Scottsdale, Arizona, United States, 85260
      • HonorHealth Scottsdale Shea Medical Center
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Ronald Reagan Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont HealthCare
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Northshore University Healthsystem
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • East Jefferson General Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Hospital - Royal Oak
  • New York
    • Jamaica, New York, United States, 11418
      • Jamaica Hospital Medical Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10019
      • Mount Sinai West
    • New York, New York, United States, 10003
      • Mount Sinai Beth Israel
    • New York, New York, United States, 10025
      • Mount Sinai Morningside
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Dallas, Texas, United States, 75226
      • Baylor Jack & Jane Hamilton Heart and Vascular Hospital
    • Fort Worth, Texas, United States, 75061
      • Baylor Scott & White All Saints Medical Center
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital Affiliated with University of Texas Health Science Center at Houston, McGovern Medical School
    • Irving, Texas, United States, 75061
      • Baylor Scott & White Medical Center
    • Plano, Texas, United States, 75093
      • Baylor Scott & White Heart Hospital
    • Plano, Texas, United States, 75093
      • Baylor Scott & White Medical Center
    • Round Rock, Texas, United States, 78665
      • Baylor Scott & White Medical Center
    • Temple, Texas, United States, 76508
      • Baylor Scott & White Medical Center
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gimsilumab; Gimsilumab 400 mg on Day 1 Gimsilumab 200 mg on Day 8	Drug: Gimsilumab; Gimsilumab is a fully human monoclonal antibody (mAb).; Other Names: KIN-1901
Placebo Comparator: Placebo; Normal saline on Day 1 Normal saline on Day 8	Drug: Placebo; Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Mortality	"Incidence" is defined as the percent of subjects that died by Day 43	Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Who Are Alive and Not on Mechanical Ventilation		Day 29
Number of Ventilator-free Days	Subjects who die will be assigned "0" ventilator-free days	Baseline to Day 29
Time to Hospital Discharge		Baseline to Day 43

Collaborators and Investigators

• Sponsor: Kinevant Sciences GmbH
• Collaborators: Roivant Sciences, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2020
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): April 1, 2021

Study Registration Dates

• First Submitted: April 15, 2020
• First Submitted That Met QC Criteria: April 15, 2020
• First Posted (Actual): April 17, 2020

Study Record Updates

• Last Update Posted (Actual): December 14, 2021
• Last Update Submitted That Met QC Criteria: December 10, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Monoclonal antibody; Coronavirus; Immunomodulator; COVID-19; Cytokine storm; Lung Injury; Severe Acute Respiratory Syndrome (SARS); Granulocyte macrophage-colony stimulating factor (GM-CSF)
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Wounds and Injuries; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Anti-Infective Agents; Antiviral Agents; Anti-Inflammatory Agents; Gimsilumab
• Other Study ID Numbers: KIN-1901-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No