Study of Sargramostim in Patients With COVID-19

COVID-19 Clinical Trial

— iLeukPulm  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04411680
• Other study ID #: PTX-001-002
• Status: Completed
• Phase: Phase 2
• Start date: August 18, 2020
• Est. completion date: May 19, 2021

Study information

• Verified date: August 2023
• Source: Partner Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: May 19, 2021
• Est. primary completion date: March 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV-2

Intervention

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.
• Standard of care
Standard of care for COVID-19

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Partner Therapeutics, Inc.	United States Department of Defense

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of Patients Who Have Been Intubated by Day 14		1-14 days
Secondary	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
Secondary	All Cause 28-day Mortality		1-28 days
Secondary	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
Secondary	Survival Time of Patients		Day 1-90
Secondary	Causes of Death		Day 1-90
Secondary	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
Secondary	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
Secondary	Number of Patients Requiring Invasive Mechanical Ventilation	The is the number of patients that needed to be placed on a ventilator.	Day 1-90
Secondary	Duration of Invasive, Non-invasive and Supplemental Oxygen	This endpoint includes duration of any/all types of respiratory support	Day 1-90
Secondary	Duration of Hospitalization		Day 1-90
Secondary	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