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

• ClinicalTrials.gov Identifier: NCT04411680
• Recruitment Status: Completed
• First Posted: June 2, 2020
• Results First Posted: February 18, 2022
• Last Update Posted: February 18, 2022
• Sponsor: Partner Therapeutics, Inc.
• Collaborator: United States Department of Defense
• Information provided by (Responsible Party): Partner Therapeutics, Inc.

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.

Condition or disease	Intervention/treatment	Phase
COVID-19; SARS-CoV-2	Drug: Sargramostim; Drug: Standard of care	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 123 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Trial Evaluating Sargramostim in Patients With COVID-19 Associated Acute Hypoxemia
• Actual Study Start Date: August 18, 2020
• Actual Primary Completion Date: March 2, 2021
• Actual Study Completion Date: May 19, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change in Oxygenation Parameter of P(A-a)O2 Gradient by Day 6 [ Time Frame: 1-6 days ]
   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.
2. Number of Patients Who Have Been Intubated by Day 14 [ Time Frame: 1-14 days ]

Secondary Outcome Measures :

1. Change in Ordinal Scale [ Time Frame: 1-28 days ]
   The ordinal scale was used, where 0 is not hospitalized, no clinical or virological evidence of infection, and 8 is death.
2. All Cause 28-day Mortality [ Time Frame: 1-28 days ]
3. Number of Patients With Treatment-related Adverse Events [ Time Frame: 1-58 days ]
   Number of patients with side effects related to treatment with sargramostim. Patients on the control arm did not receive sargramostim.
4. Survival Time of Patients [ Time Frame: Day 1-90 ]
5. Causes of Death [ Time Frame: Day 1-90 ]
6. Change From Baseline in P/F Ratio [ Time Frame: From Day 1 up to Day 6 ]

   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.

7. Number of Participants Wtih Nosocomial Infections [ Time Frame: Day 1-90 ]
   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.
8. Number of Patients Requiring Invasive Mechanical Ventilation [ Time Frame: Day 1-90 ]
   The is the number of patients that needed to be placed on a ventilator.
9. Duration of Invasive, Non-invasive and Supplemental Oxygen [ Time Frame: Day 1-90 ]
   This endpoint includes duration of any/all types of respiratory support
10. Duration of Hospitalization [ Time Frame: Day 1-90 ]
11. Time to Normalization of White Blood Cells and Lymphocytes [ Time Frame: Day 1-90 ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

St. Jude Medical Center

Fullerton, California, United States, 92835

St. Joseph Hospital of Orange

Orange, California, United States, 92868

California Pacific Medical Center - Van Ness Campus

San Francisco, California, United States, 94109

United States, Maryland

TidalHealth Peninsula Regional, Inc

Salisbury, Maryland, United States, 21801

United States, Missouri

University of Missouri Health Care

Columbia, Missouri, United States, 65212

United States, Nebraska

Great Plains Health

North Platte, Nebraska, United States, 69101

United States, New York

Richmond University Medical Center

Staten Island, New York, United States, 10310

United States, North Carolina

Brody School of Medicine at East Carolina University

Greenville, North Carolina, United States, 27834

United States, Ohio

University of Toledo Medical Center

Toledo, Ohio, United States, 43614

United States, Texas

Memorial Hermann Hospital Affiliated with the University of Texas Health Science Center at Houston, McGovern Medical School

Houston, Texas, United States, 77030

United States, Utah

University of Utah Health

Salt Lake City, Utah, United States, 84108

Sponsors and Collaborators

Partner Therapeutics, Inc.

United States Department of Defense

Investigators

• Study Director: Medical Information; Partner Therapeutics, Inc.

  Study Documents (Full-Text)

Documents provided by Partner Therapeutics, Inc.:

Study Protocol  [PDF] December 2, 2020

Statistical Analysis Plan  [PDF] March 17, 2021

More Information

• Responsible Party: Partner Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT04411680
• Other Study ID Numbers: PTX-001-002
• First Posted: June 2, 2020
• Results First Posted: February 18, 2022
• Last Update Posted: February 18, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Partner Therapeutics, Inc.:

COVID-19; sargramostim; Leukine; rhu-GM-CSF; acute hypoxemia; iLeukPulm; SARS-CoV-2

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Sargramostim; Immunologic Factors; Physiological Effects of Drugs