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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04351243
Recruitment Status : Completed
First Posted : April 17, 2020
Results First Posted : December 10, 2021
Last Update Posted : December 14, 2021
Sponsor:
Collaborator:
Roivant Sciences, Inc.
Information provided by (Responsible Party):
Kinevant Sciences GmbH

Tracking Information
First Submitted Date  ICMJE April 15, 2020
First Posted Date  ICMJE April 17, 2020
Results First Submitted Date  ICMJE November 26, 2021
Results First Posted Date  ICMJE December 10, 2021
Last Update Posted Date December 14, 2021
Actual Study Start Date  ICMJE April 15, 2020
Actual Primary Completion Date December 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 6, 2021)
Incidence of Mortality [ Time Frame: Day 43 ]
"Incidence" is defined as the percent of subjects that died by Day 43
Original Primary Outcome Measures  ICMJE
 (submitted: April 15, 2020)
Primary endpoint [ Time Frame: 43 days ]
Incidence of mortality by Day 43
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 26, 2021)
  • Proportion of Subjects Who Are Alive and Not on Mechanical Ventilation [ Time Frame: Day 29 ]
  • Number of Ventilator-free Days [ Time Frame: Baseline to Day 29 ]
    Subjects who die will be assigned "0" ventilator-free days
  • Time to Hospital Discharge [ Time Frame: Baseline to Day 43 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2020)
  • Secondary endpoint [ Time Frame: Day 43 ]
    To assess the effect of gimsilumab on ventilation requirements
  • Secondary endpoint [ Time Frame: Day 43 ]
    To assess the effect of gimsilumab on the need for Intensive Care Unit level of care
  • Secondary endpoint [ Time Frame: Day 43 ]
    To assess the effect of gimsilumab on overall duration of hospitalization
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Drug: Gimsilumab
    Gimsilumab is a fully human monoclonal antibody (mAb).
    Other Name: KIN-1901
  • Drug: Placebo
    Normal saline
Study Arms  ICMJE
  • Experimental: Gimsilumab
    Gimsilumab 400 mg on Day 1 Gimsilumab 200 mg on Day 8
    Intervention: Drug: Gimsilumab
  • Placebo Comparator: Placebo
    Normal saline on Day 1 Normal saline on Day 8
    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 28, 2020)
227
Original Estimated Enrollment  ICMJE
 (submitted: April 15, 2020)
270
Actual Study Completion Date  ICMJE April 1, 2021
Actual Primary Completion Date December 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04351243
Other Study ID Numbers  ICMJE KIN-1901-2001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Kinevant Sciences GmbH
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Kinevant Sciences GmbH
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Roivant Sciences, Inc.
Investigators  ICMJE Not Provided
PRS Account Kinevant Sciences GmbH
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP