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

A Phase 2 Trial Evaluating Sargramostim in Patients With COVID-19 Associated Acute Hypoxemia

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; SARS-CoV-2
• Intervention / Treatment: Drug: Sargramostim; Drug: Standard of care

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.

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Fullerton, California, United States, 92835
      • St. Jude Medical Center
    • Orange, California, United States, 92868
      • St. Joseph Hospital of Orange
    • San Francisco, California, United States, 94109
      • California Pacific Medical Center - Van Ness Campus
  • Maryland
    • Salisbury, Maryland, United States, 21801
      • TidalHealth Peninsula Regional, Inc
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri Health Care
  • Nebraska
    • North Platte, Nebraska, United States, 69101
      • Great Plains Health
  • New York
    • Staten Island, New York, United States, 10310
      • Richmond University Medical Center
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Brody School of Medicine at East Carolina University
  • Ohio
    • Toledo, Ohio, United States, 43614
      • University of Toledo Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital Affiliated with the University of Texas Health Science Center at Houston, McGovern Medical School
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sargramostim Arm; Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19	Drug: Sargramostim; 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.; Other Names: Leukine; GM-CSF; Drug: Standard of care; Standard of care for COVID-19
Active Comparator: Control Arm; Standard of care for COVID-19	Drug: Standard of care; Standard of care for COVID-19

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1-6 days
Number of Patients Who Have Been Intubated by Day 14		1-14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1-28 days
All Cause 28-day Mortality		1-28 days
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.	1-58 days
Survival Time of Patients		Day 1-90
Causes of Death		Day 1-90
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.	From Day 1 up to Day 6
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.	Day 1-90
Number of Patients Requiring Invasive Mechanical Ventilation	The is the number of patients that needed to be placed on a ventilator.	Day 1-90
Duration of Invasive, Non-invasive and Supplemental Oxygen	This endpoint includes duration of any/all types of respiratory support	Day 1-90
Duration of Hospitalization		Day 1-90
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.	Day 1-90

Collaborators and Investigators

• Sponsor: Partner Therapeutics, Inc.
• Collaborators: United States Department of Defense
• Investigators: Study Director: Medical Information, Partner Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2020
• Primary Completion (Actual): March 2, 2021
• Study Completion (Actual): May 19, 2021

Study Registration Dates

• First Submitted: May 29, 2020
• First Submitted That Met QC Criteria: May 29, 2020
• First Posted (Actual): June 2, 2020

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; Leukine; sargramostim; rhu-GM-CSF; acute hypoxemia; iLeukPulm
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Sargramostim
• Other Study ID Numbers: PTX-001-002

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