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Study of Sargramostim in Patients With COVID-19 (iLeukPulm)

Primary Purpose

COVID-19, SARS-CoV-2

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sargramostim
Standard of care
Sponsored by
Partner Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring COVID-19, sargramostim, Leukine, rhu-GM-CSF, acute hypoxemia, iLeukPulm, SARS-CoV-2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients aged ≥ 18 years
  • Patients (or legally authorized decision maker) must provide informed consent
  • Test positive for SARS-CoV-2 virus by PCR
  • Admitted to hospital

  • Presence of acute hypoxemia defined as (either or both)

    • saturation below 93% on ≥ 2 L/min oxygen supplementation
    • PaO2/FiO2 below 350

Exclusion Criteria:

  • Patients requiring invasive (mechanical ventilation) or non-invasive (CPAP, BiPAP for hypoxemia) ventilation or ECMO (Note: oxygen supplementation using high flow oxygen systems or low flow oxygen systems would not exclude patients from this study)
  • Intractable metabolic acidosis
  • Cardiogenic pulmonary edema
  • Hypotension requiring use of vasopressors
  • Hyperferritinemia (serum ferritin ≥2,000 mcg/L)
  • White blood cell count > 50,000/mm3
  • Participation in another interventional clinical trial for COVID-19 therapy
  • Highly immunosuppressive therapy or anti-cancer combination chemotherapy within 24 hours prior to first dose of sargramostim
  • Known or suspected intolerance or hypersensitivity to sargramostim, or any component of the product
  • Previous experience of severe and unexplained side effects during aerosol delivery of any kind of medical product
  • Presence of any preexisting illness that, in the opinion of the Investigator, would place the patient at an unreasonably increased risk through participation in this study
  • Pregnant or breastfeeding females
  • Severe or uncontrolled pulmonary comorbid conditions, including systemic steroid dependent asthma, systemic steroid dependent COPD, oxygen dependent COPD, lung transplant, known interstitial lung disease, or cystic fibrosis

Sites / Locations

  • St. Jude Medical Center
  • St. Joseph Hospital of Orange
  • California Pacific Medical Center - Van Ness Campus
  • TidalHealth Peninsula Regional, Inc
  • University of Missouri Health Care
  • Great Plains Health
  • Richmond University Medical Center
  • Brody School of Medicine at East Carolina University
  • University of Toledo Medical Center
  • Memorial Hermann Hospital Affiliated with the University of Texas Health Science Center at Houston, McGovern Medical School
  • University of Utah Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Sargramostim Arm

Control Arm

Arm Description

Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19

Standard of care for COVID-19

Outcomes

Primary Outcome Measures

Change in Oxygenation Parameter of P(A-a)O2 Gradient by Day 6
The P(A-a)O2 gradient is a measure of how well the oxygen moves from the lungs into the bloodstream. Patients with a high gradient have less oxygen in the bloodstream.
Number of Patients Who Have Been Intubated by Day 14

Secondary Outcome Measures

Change in Ordinal Scale
The ordinal scale was used, where 0 is not hospitalized, no clinical or virological evidence of infection, and 8 is death.
All Cause 28-day Mortality
Number of Patients With Treatment-related Adverse Events
Number of patients with side effects related to treatment with sargramostim. Patients on the control arm did not receive sargramostim.
Survival Time of Patients
Causes of Death
Change From Baseline in P/F Ratio
The P/F ratio is a simple way to assess severity of low blood oxygen. It's the ratio of PaO2 (arterial oxygen partial pressure obtained from an arterial blood gas) to FiO2 (fraction of inspired oxygen expressed as a decimal). A normal arterial blood is gas 80 to 100 mm Hg. Normal room air has 21% or 0.21 oxygen. So a "normal" P/F ratio is about 380-475. A high P/F ratio means more oxygen in the bloodstream and a low P/F ratio means less oxygen in the bloodstream. This outcome measure compares the improvement (increase) in P/F ratio between treatment arms.
Number of Participants Wtih Nosocomial Infections
Nosocomial infections also referred to as healthcare-associated infections (HAI), are infection(s) acquired during the process of receiving health care that was not present during the time of admission.
Number of Patients Requiring Invasive Mechanical Ventilation
The is the number of patients that needed to be placed on a ventilator.
Duration of Invasive, Non-invasive and Supplemental Oxygen
This endpoint includes duration of any/all types of respiratory support
Duration of Hospitalization
Time to Normalization of White Blood Cells and Lymphocytes
Normalization of WBC and lymphocyte count is defined as whether WBC and lymphocyte count results are normal or below normal or above normal ranges at available visits.

Full Information

First Posted
May 29, 2020
Last Updated
August 7, 2023
Sponsor
Partner Therapeutics, Inc.
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT04411680
Brief Title
Study of Sargramostim in Patients With COVID-19
Acronym
iLeukPulm
Official Title
A Phase 2 Trial Evaluating Sargramostim in Patients With COVID-19 Associated Acute Hypoxemia
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
August 18, 2020 (Actual)
Primary Completion Date
March 2, 2021 (Actual)
Study Completion Date
May 19, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Partner Therapeutics, Inc.
Collaborators
United States Department of Defense

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
The purpose of this research is to find out if a drug (sargramostim) also known as Leukine® could help patient recover faster from COVID-19. Sargramostim may help the lungs recover from the effects of COVID-19, and this research study will help to find this out.
Detailed Description
This Phase 2 study is designed as a proof of concept study and will randomize 2:1 approximately 120 patients with COVID-19 associated acute hypoxemia: of which 80 patients will receive sargramostim plus standard of care, and 40 patients who will receive standard of care alone. The aim of the study is to determine if inhaled sargramostim, as an adjunct to institutional standard of care, improves clinical outcomes in patients with COVID-19-associated acute hypoxemia. All patients on the sargramostim arm will be treated with 125 mcg inhaled sargramostim twice daily for 5 days, in addition to institutional standard of care. If required, upon progression to an invasive mechanical ventilator, administration of sargramostim may be delivered by intravenous infusion to complete a total of 5 days (including days delivered via inhalation). GM-CSF is a critical cytokine for healthy pulmonary function and is necessary for the maturation and maintenance of alveolar macrophages. Preclinical studies have shown GM-CSF confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages for their health and normal functioning. Clinical studies of sargramostim in patients with severe sepsis and respiratory dysfunction or acute respiratory distress syndrome have shown improvements in oxygenation and lung compliance.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, SARS-CoV-2
Keywords
COVID-19, sargramostim, Leukine, rhu-GM-CSF, acute hypoxemia, iLeukPulm, SARS-CoV-2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
This Phase 2, randomized, open-label study will enroll approximately 120 patients with COVID-19 associated acute hypoxemia. It is a randomized 2:1 study to evaluate sargramostim treatment plus institutional standard of care compared to institutional standard of care alone.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
123 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sargramostim Arm
Arm Type
Experimental
Arm Description
Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19
Arm Title
Control Arm
Arm Type
Active Comparator
Arm Description
Standard of care for COVID-19
Intervention Type
Drug
Intervention Name(s)
Sargramostim
Other Intervention Name(s)
Leukine, GM-CSF
Intervention Description
Sargramostim is a glycosylated, yeast-derived recombinant human granulocyte-macrophage colony stimulating factor (rhu-GM-CSF). Dosage for inhaled sargramostim: 125 mcg twice a day. Dosage for intravenous sargramostim: 125mcg/m2/day given over a 4 hour period.
Intervention Type
Drug
Intervention Name(s)
Standard of care
Intervention Description
Standard of care for COVID-19
Primary Outcome Measure Information:
Title
Change in Oxygenation Parameter of P(A-a)O2 Gradient by Day 6
Description
The P(A-a)O2 gradient is a measure of how well the oxygen moves from the lungs into the bloodstream. Patients with a high gradient have less oxygen in the bloodstream.
Time Frame
1-6 days
Title
Number of Patients Who Have Been Intubated by Day 14
Time Frame
1-14 days
Secondary Outcome Measure Information:
Title
Change in Ordinal Scale
Description
The ordinal scale was used, where 0 is not hospitalized, no clinical or virological evidence of infection, and 8 is death.
Time Frame
1-28 days
Title
All Cause 28-day Mortality
Time Frame
1-28 days
Title
Number of Patients With Treatment-related Adverse Events
Description
Number of patients with side effects related to treatment with sargramostim. Patients on the control arm did not receive sargramostim.
Time Frame
1-58 days
Title
Survival Time of Patients
Time Frame
Day 1-90
Title
Causes of Death
Time Frame
Day 1-90
Title
Change From Baseline in P/F Ratio
Description
The P/F ratio is a simple way to assess severity of low blood oxygen. It's the ratio of PaO2 (arterial oxygen partial pressure obtained from an arterial blood gas) to FiO2 (fraction of inspired oxygen expressed as a decimal). A normal arterial blood is gas 80 to 100 mm Hg. Normal room air has 21% or 0.21 oxygen. So a "normal" P/F ratio is about 380-475. A high P/F ratio means more oxygen in the bloodstream and a low P/F ratio means less oxygen in the bloodstream. This outcome measure compares the improvement (increase) in P/F ratio between treatment arms.
Time Frame
From Day 1 up to Day 6
Title
Number of Participants Wtih Nosocomial Infections
Description
Nosocomial infections also referred to as healthcare-associated infections (HAI), are infection(s) acquired during the process of receiving health care that was not present during the time of admission.
Time Frame
Day 1-90
Title
Number of Patients Requiring Invasive Mechanical Ventilation
Description
The is the number of patients that needed to be placed on a ventilator.
Time Frame
Day 1-90
Title
Duration of Invasive, Non-invasive and Supplemental Oxygen
Description
This endpoint includes duration of any/all types of respiratory support
Time Frame
Day 1-90
Title
Duration of Hospitalization
Time Frame
Day 1-90
Title
Time to Normalization of White Blood Cells and Lymphocytes
Description
Normalization of WBC and lymphocyte count is defined as whether WBC and lymphocyte count results are normal or below normal or above normal ranges at available visits.
Time Frame
Day 1-90

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients aged ≥ 18 years Patients (or legally authorized decision maker) must provide informed consent Test positive for SARS-CoV-2 virus by PCR Admitted to hospital Presence of acute hypoxemia defined as (either or both) saturation below 93% on ≥ 2 L/min oxygen supplementation PaO2/FiO2 below 350 Exclusion Criteria: Patients requiring invasive (mechanical ventilation) or non-invasive (CPAP, BiPAP for hypoxemia) ventilation or ECMO (Note: oxygen supplementation using high flow oxygen systems or low flow oxygen systems would not exclude patients from this study) Intractable metabolic acidosis Cardiogenic pulmonary edema Hypotension requiring use of vasopressors Hyperferritinemia (serum ferritin ≥2,000 mcg/L) White blood cell count > 50,000/mm3 Participation in another interventional clinical trial for COVID-19 therapy Highly immunosuppressive therapy or anti-cancer combination chemotherapy within 24 hours prior to first dose of sargramostim Known or suspected intolerance or hypersensitivity to sargramostim, or any component of the product Previous experience of severe and unexplained side effects during aerosol delivery of any kind of medical product Presence of any preexisting illness that, in the opinion of the Investigator, would place the patient at an unreasonably increased risk through participation in this study Pregnant or breastfeeding females Severe or uncontrolled pulmonary comorbid conditions, including systemic steroid dependent asthma, systemic steroid dependent COPD, oxygen dependent COPD, lung transplant, known interstitial lung disease, or cystic fibrosis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Information
Organizational Affiliation
Partner Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
St. Jude Medical Center
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
Facility Name
St. Joseph Hospital of Orange
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
California Pacific Medical Center - Van Ness Campus
City
San Francisco
State/Province
California
ZIP/Postal Code
94109
Country
United States
Facility Name
TidalHealth Peninsula Regional, Inc
City
Salisbury
State/Province
Maryland
ZIP/Postal Code
21801
Country
United States
Facility Name
University of Missouri Health Care
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
Facility Name
Great Plains Health
City
North Platte
State/Province
Nebraska
ZIP/Postal Code
69101
Country
United States
Facility Name
Richmond University Medical Center
City
Staten Island
State/Province
New York
ZIP/Postal Code
10310
Country
United States
Facility Name
Brody School of Medicine at East Carolina University
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
University of Toledo Medical Center
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43614
Country
United States
Facility Name
Memorial Hermann Hospital Affiliated with the University of Texas Health Science Center at Houston, McGovern Medical School
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah Health
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36458916
Citation
Paine R, Chasse R, Halstead ES, Nfonoyim J, Park DJ, Byun T, Patel B, Molina-Pallete G, Harris ES, Garner F, Simms L, Ahuja S, McManus JL, Roychowdhury DF. Inhaled Sargramostim (Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor) for COVID-19-Associated Acute Hypoxemia: Results of the Phase 2, Randomized, Open-Label Trial (iLeukPulm). Mil Med. 2022 Dec 2;188(7-8):e2629-38. doi: 10.1093/milmed/usac362. Online ahead of print.
Results Reference
result

Learn more about this trial

Study of Sargramostim in Patients With COVID-19

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