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| Name | Class |
|---|---|
| United States Department of Defense | FED |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sargramostim Arm | Experimental | Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 |
|
| Control Arm | Active Comparator | Standard of care for COVID-19 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sargramostim | Drug | 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. |
| 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 |
| 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 |
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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)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Information | Partner Therapeutics, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Jude Medical Center | Fullerton | California | 92835 | United States | ||
| St. Joseph Hospital of Orange |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36458916 | Result | 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. |
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One participant was randomized to the sargramostim arm and then withdrew consent prior to treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sargramostim Arm | Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a 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 |
| FG001 | Control Arm | Standard of care for COVID-19 Standard of care: Standard of care for COVID-19 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Period |
|
| |||||||||||||||||||||
| Follow up Period |
|
One patient was randomized to the Sargramostim Arm, but was not treated.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sargramostim Arm | Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Patients analyzed if they had both a baseline and at least 1 post-baseline measurement. | Posted | Least Squares Mean | Standard Error | millimeters of mercury (mmHg) | 1-6 days |
|
Adverse Events: Day 1-58, All-Cause Mortality: Day 1-90
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sargramostim Arm | Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19 Sargramostim: Sargramostim is a 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA v.23.1 | Systematic Assessment | Abnormal heartbeat |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA v.23.1 | Systematic Assessment | Not enough red blood cells |
Limitations include lack of a blinded placebo control and reliance on ABG measurement for estimation of P(A-a)O2 gradient. Some clinical endpoints trial might have been affected by observer bias, availability of hospital or ICU resources, and/or hospital discharge. Missing ABG measurements may have resulted from decreased standard utilization of ABG in recent years, and hospital staff overload due to the COVID-19 pandemic may have led to absent follow-up assessment.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Information | Partner Therapeutics, Inc. | 1-888-479-5385 | PartnerTx@medcomminc.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 2, 2020 | Jan 25, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 17, 2021 | Jan 25, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C081222 | sargramostim |
| D016178 | Granulocyte-Macrophage Colony-Stimulating Factor |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
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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.
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|
|
| Standard of care | Drug | Standard of care for COVID-19 |
|
| 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 |
| Orange |
| California |
| 92868 |
| United States |
| California Pacific Medical Center - Van Ness Campus | San Francisco | California | 94109 | United States |
| TidalHealth Peninsula Regional, Inc | Salisbury | Maryland | 21801 | United States |
| University of Missouri Health Care | Columbia | Missouri | 65212 | United States |
| Great Plains Health | North Platte | Nebraska | 69101 | United States |
| Richmond University Medical Center | Staten Island | New York | 10310 | United States |
| Brody School of Medicine at East Carolina University | Greenville | North Carolina | 27834 | United States |
| University of Toledo Medical Center | Toledo | Ohio | 43614 | United States |
| Memorial Hermann Hospital Affiliated with the University of Texas Health Science Center at Houston, McGovern Medical School | Houston | Texas | 77030 | United States |
| University of Utah Health | Salt Lake City | Utah | 84108 | United States |
| Missed 1 or more doses |
|
| Transferred to another hospital |
|
| NOT COMPLETED |
|
|
| BG001 | Control Arm | Standard of care for COVID-19 Standard of care: Standard of care for COVID-19 |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Body Mass Index | Data to calculate BMI is missing for 5 patients in sargramostim arm and 1 patient in control arm. | Mean | Standard Deviation | kilograms/meter squared |
|
| OG001 |
| Control Arm |
Standard of care for COVID-19 Standard of care: Standard of care for COVID-19 |
|
|
| Primary | Number of Patients Who Have Been Intubated by Day 14 | Posted | Count of Participants | Participants | 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. | Only 86 patients had follow up data at Day 28 | Posted | Mean | Standard Deviation | score on a scale | 1-28 days |
|
|
|
| Secondary | All Cause 28-day Mortality | Posted | Count of Participants | Participants | 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. | Posted | Count of Participants | Participants | 1-58 days |
|
|
|
| Secondary | Survival Time of Patients | Posted | Mean | Standard Deviation | Days | Day 1-90 |
|
|
|
| Secondary | Causes of Death | Patients alive at Day 90 were not analyzed | Posted | Count of Participants | Participants | 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. | Patients were analyzed if they had both a baseline and at least 1 post-baseline measurement of P/F ratio. | Posted | Mean | Standard Deviation | ratio | 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. | Posted | Count of Participants | Participants | 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. | Posted | Count of Participants | Participants | Day 1-90 |
|
|
|
| Secondary | Duration of Invasive, Non-invasive and Supplemental Oxygen | This endpoint includes duration of any/all types of respiratory support | Posted | Mean | Standard Deviation | Days | Day 1-90 |
|
|
|
| Secondary | Duration of Hospitalization | Posted | Mean | Standard Deviation | Days | 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. | Of 78 and 44 participants in the Sargramostim and Control Arms, respectively, only 28 (35.8%) and 17 (38.6%) had both baseline and post-baseline values available for evaluation at the Day 6 timepoint of interest. | Posted | Mean | Standard Deviation | Days | Day 1-90 |
|
|
|
| 11 |
| 78 |
| 15 |
| 78 |
| 47 |
| 78 |
| EG001 | Control Arm | Standard of care for COVID-19 Standard of care: Standard of care for COVID-19 | 8 | 44 | 14 | 44 | 30 | 44 |
|
| Atrial flutter | Cardiac disorders | MedDRA v.23.1 | Systematic Assessment | Abnormal heartbeat |
|
| Cardio-respiratory arrest | Cardiac disorders | MedDRA v.23.1 | Systematic Assessment |
|
| Cardiac death | General disorders | MedDRA v.23.1 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA v.23.1 | Systematic Assessment | Skin infection |
|
| Septic shock | Infections and infestations | MedDRA v.23.1 | Systematic Assessment | Shock due to infection |
|
| False positive investigation result | Investigations | MedDRA v.23.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA v.23.1 | Systematic Assessment | Too much potassium in the blood stream |
|
| Alcohol withdrawal syndrome | Psychiatric disorders | MedDRA v.23.1 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA v.23.1 | Systematic Assessment |
|
| Anuria | Renal and urinary disorders | MedDRA v.23.1 | Systematic Assessment | Absence of urination |
|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA v.23.1 | Systematic Assessment |
|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA v.23.1 | Systematic Assessment | Emphysema |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA v.23.1 | Systematic Assessment | Not enough oxygen in the bloodstream |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA v.23.1 | Systematic Assessment | Blood clot in the lungs |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA v.23.1 | Systematic Assessment | Term respiratory failure includes terms respiratory failure, acute respiratory failure and chronic respiratory failure |
|
|
| Constipation | Gastrointestinal disorders | MedDRA v.23.1 | Systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA v.23.1 | Systematic Assessment | Shock due to infection |
|
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA v.23.1 | Systematic Assessment | Too much glucose in the bloodstream |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v.23.1 | Systematic Assessment | Too little potassium in the bloodstream |
|
| Anxiety | Psychiatric disorders | MedDRA v.23.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA v.23.1 | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA v.23.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA v.23.1 | Systematic Assessment | Low blood pressure |
|
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| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D016298 |
| Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Cardiorespiratory arrest |
|
| Septic shock |
|