Clinical trial NCT04411680: Study of Sargramostim in Patients With COVID-19
Official title: A Phase 2 Trial Evaluating Sargramostim in Patients With COVID-19 Associated Acute Hypoxemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
SARS-CoV-2
Keywords: COVID-19
sargramostim
Leukine
rhu-GM-CSF
acute hypoxemia
iLeukPulm
SARS-CoV-2
Lead sponsor: Partner Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: United States Department of Defense
First posted: 2020-06-02
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Oxygenation Parameter of P(A-a)O2 Gradient by Day 6
timeFrame: 1-6 days
measure: Number of Patients Who Have Been Intubated by Day 14
timeFrame: 1-14 days
Secondary outcomes:
measure: Change in Ordinal Scale
timeFrame: 1-28 days
measure: All Cause 28-day Mortality
timeFrame: 1-28 days
measure: Number of Patients With Treatment-related Adverse Events
timeFrame: 1-58 days
measure: Survival Time of Patients
timeFrame: Day 1-90
measure: Causes of Death
timeFrame: Day 1-90
measure: Change From Baseline in P/F Ratio
timeFrame: From Day 1 up to Day 6
measure: Number of Participants Wtih Nosocomial Infections
timeFrame: Day 1-90
measure: Number of Patients Requiring Invasive Mechanical Ventilation
timeFrame: Day 1-90
measure: Duration of Invasive, Non-invasive and Supplemental Oxygen
timeFrame: Day 1-90
measure: Duration of Hospitalization
timeFrame: Day 1-90
measure: Time to Normalization of White Blood Cells and Lymphocytes
timeFrame: Day 1-90
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: St. Jude Medical Center
state: California
city: Orange
country: United States
facility: St. Joseph Hospital of Orange
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center - Van Ness Campus
state: California
city: Salisbury
country: United States
facility: TidalHealth Peninsula Regional, Inc
state: Maryland
city: Columbia
country: United States
facility: University of Missouri Health Care
state: Missouri
city: North Platte
country: United States
facility: Great Plains Health
state: Nebraska
city: Staten Island
country: United States
facility: Richmond University Medical Center
state: New York
city: Greenville
country: United States
facility: Brody School of Medicine at East Carolina University
state: North Carolina
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Houston
country: United States
facility: Memorial Hermann Hospital Affiliated with the University of Texas Health Science Center at Houston, McGovern Medical School
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
Study officials:
affiliation: Partner Therapeutics, Inc.
name: Medical Information
role: STUDY_DIRECTOR
References:
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. 2023 Jul 22;188(7-8):e2629-e2638. doi: 10.1093/milmed/usac362.