Sargramostim Use in COVID-19 to Recover Patient Health

Covid19 Clinical Trial

— SCOPE  

Official title:

A Randomized Phase 2b Trial Evaluating Clinical Outcomes of Inhaled Sargramostim in High-risk Patients With Mild-moderate COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04707664
• Other study ID #: PTX-001-003
• Status: Completed
• Phase: Phase 2
• Start date: April 27, 2021
• Est. completion date: January 31, 2022

Study information

• Verified date: December 2022
• Source: Partner Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this research is to understand if the study drug, also called sargramostim or Leukine®, can help prevent the worsening of COVID-19 when the study drug is inhaled. This study will also help researchers understand if inhaled sargramostim can help prevent visits to the emergency room or hospitalization, or death.

Description:

This Phase 2b, multicenter, placebo-controlled, double-blind study will randomize approximately 500 adult patients who are symptomatic with mild or moderate COVID-19 (as defined in the FDA Guidance Document: Covid-19: Developing Drugs and Biological Products for Treatment or Prevention, May 2020) who are at high risk for progression to more severe disease. Patients will be randomized in a 1:1 ratio to inhaled sargramostim plus standard of care (SOC) or placebo plus SOC. Enrollment of patients who have completed a COVID-19 vaccination regimen or participated in a COVID-19 vaccine clinical trial will be capped at approximately 100 patients. All patients will be randomized to receive either 250 mcg of sargramostim or equivalent volume of placebo diluent. Treatment will be administered once daily for 5 days delivered via a vibrating mesh nebulizer. Patients will be followed for up to 60 days after start of treatment.

Sargramostim (Leukine) is a formulation of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), which is a critical cytokine for healthy pulmonary function. Detailed studies have shown that GM-CSF is necessary for alveolar macrophage (AM) maturation and maintenance. Although GM-CSF was discovered as a myelopoietic growth factor, it has diverse additional effects that both promote differentiation of myeloid precursors into neutrophils, monocytes, and dendritic cells and control function of mature myeloid cells. GM-CSF is also known to reverse immunoparalysis seen in sepsis, resulting in beneficial outcomes. In addition, GM-CSF prevents bacteremia in post influenza bacterial pneumonia through locally mediated improved lung antibacterial resistance and increased reactive oxygen species production by AMs. Pulmonary delivery of this GM-CSF has potential to reduce morbidity and mortality due to viral pneumonias, potentially including COVID-19.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: January 31, 2022
• Est. primary completion date: December 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients with a positive laboratory diagnosis of SARS-CoV-2 infection by an antigen or a molecular test =5 days prior to randomization. The test should have been authorized by the relevant regulatory authority.

2. Have one or more of the following mild or moderate COVID-19 symptoms for =5 days prior to randomization:

1. Fever or chills

2. New onset or worsening cough

3. Sore throat

4. Malaise or fatigue

5. Headache

6. Muscle pain (myalgias) or body aches

7. Gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea)

8. New onset or worsening shortness of breath or difficulty breathing

9. Nasal congestion or runny nose

10. New loss of taste (ageusia) and/or smell (anosmia). Note: any of these symptoms (ageusia, anosmia) alone or in combination cannot be used as the SOLE qualifying symptoms for enrollment.

3. At higher risk for progression to more severe COVID-19

1. Age = 60 years

2. Age 18-59 years with a clinically stable medical history of at least 1 or more of the following conditions that could lead to severe COVID-19:

• Chronic respiratory conditions such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis

• Obesity with BMI = 30 kg/m2

• Cardiovascular disease

• Sickle cell disease or thalassemia

• Diabetes mellitus being managed with concomitant medications

• Hypertension being managed with concomitant medications

• Chronic kidney disease

4. Oxygen saturation by pulse oximeter > 93% on room air. Note: at altitudes of >4000 feet above sea level, oxygen saturation by pulse oximeter > 91% on room air is permitted

5. Negative pregnancy test (if woman of childbearing potential)

6. Females of childbearing potential and males with female partners of childbearing potential must agree to use acceptable contraceptive methods from screening to Day 28

7. The patient (or legally authorized decision maker) must give informed consent

Exclusion Criteria:

1. Hospitalized patients

2. Patients who have received or are receiving other treatments that are not approved/authorized by the relevant regulatory authority for the treatment of patients with mild or moderate COVID-19 in an outpatient setting

3. Patients enrolled in interventional clinical trials for other experimental therapies

4. Patients on chronic oxygen supplementation due to cardiopulmonary or other conditions

5. Patients with unstable comorbid conditions (e.g., decompensated congestive heart failure, COPD with exacerbation, current angina pectoris, uncontrolled diabetes mellitus, uncontrolled hypertension, uncontrolled asthma)

6. Patients with severe pulmonary comorbid conditions, including systemic steroid-dependent asthma, systemic steroid-dependent COPD, oxygen-dependent COPD, lung transplant, or cystic fibrosis

7. Patients who have received highly immunosuppressive therapy (to include systemic corticosteroids) or anti-cancer combination chemotherapy within 24 hours prior to first dose of study drug

8. Patients with known or suspected intolerance or hypersensitivity to sargramostim, or any component of the product

9. Patients who have previously experienced severe and unexplained side effects during aerosol delivery of any kind of medical product

10. Pregnant or breastfeeding females

11. Patients who, in the opinion of the Investigator, will not be able to comply with all the study procedures and visits as outlined in the schedule of events, including follow-up

Related Conditions & MeSH terms

• COVID-19
• Covid19
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

Drug:
• Sargramostim
All patients randomized to the sargramostim treatment arm will be treated with 250 mcg inhaled sargramostim administered via a vibrating mesh nebulizer once daily for 5 days.
• Placebo
All patients in the control arm will receive an equivalent volume of inhaled placebo diluent administered via a vibrating mesh nebulizer once daily for 5 days.

Locations

Country	Name	City	State
Argentina	Sanatorio Santa Barbara	Buenos Aires
Argentina	Centro de Investigaciones Medicas Mar del Plata	Mar del Plata	Buenos Aires
Argentina	Instituto Medico de la Fundacion Estudios Clinicos	Rosario	Santa Fe
United States	Synergy Healthcare	Bradenton	Florida
United States	Gwinnett Research Institute, LLC	Buford	Georgia
United States	Hope Clinical Research	Canoga Park	California
United States	University Diabetes & Endocrine Consultants	Chattanooga	Tennessee
United States	Hometown Urgent Care and Research	Cincinnati	Ohio
United States	Paramount Research Solutions	College Park	Georgia
United States	Benchmark Research	Colton	California
United States	Hometown Urgent Care and Research	Columbus	Ohio
United States	UCCT @ City Doc Urgent Care-McKinney	Dallas	Texas
United States	Urgent Care Specialists, LLC DBA Hometown Urgent Care and Research	Dayton	Ohio
United States	TruCare Internal Medicine and Infectious Disease	DuBois	Pennsylvania
United States	Urgent Care Clinical Trials @ AFC Urgent Care - Easley	Easley	South Carolina
United States	Invesclinic US LLC	Edinburg	Texas
United States	Revive Research Institute, Inc.	Farmington Hills	Michigan
United States	Invesclinic US, LLC.	Fort Lauderdale	Florida
United States	Indago Research & Health Center, Inc. (Subject Visits Only)	Hialeah	Florida
United States	Encore Medical Research	Hollywood	Florida
United States	Dorrington Medical Associates	Houston	Texas
United States	Encore Imaging & Medical Research	Houston	Texas
United States	Excel Clinical Research	Las Vegas	Nevada
United States	Applied Research Center of Arkansas	Little Rock	Arkansas
United States	SMS Clinical Research, LLC	Mesquite	Texas
United States	Monroe Biomedical Research	Monroe	North Carolina
United States	Great Plains Health	North Platte	Nebraska
United States	Olive Branch Family Medical Center	Olive Branch	Mississippi
United States	IMIC Inc.	Palmetto Bay	Florida
United States	Novotrial Research Group	Pearland	Texas
United States	West Valley Research Clinic, LLC	Phoenix	Arizona
United States	TidalHealth Peninsula Regional, Inc.	Salisbury	Maryland
United States	University of Utah Health	Salt Lake City	Utah
United States	Sun Research Institute	San Antonio	Texas
United States	Richmond University Medical Center	Staten Island	New York
United States	Revival Research Institute, LLC.	Sterling Heights	Michigan
United States	Encore Medical Research of Weston	Weston	Florida

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Argentina, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With an Emergency Room Visit or Hospitalization, or Death by Day 28	Percentage of patients who experience any emergency room visit or hospitalization, or death	28 days
Secondary	Disease Progression Based on NIAID Score	Proportion of patients with any progression of disease as determined by a = 2-point increase from baseline in the National Institute of Allergy and Infectious Disease (NIAID) Ordinal Scale up to Day 28, and Day 60. The NIAID Ordinal Scale is a 1-8 scale and is an assessment of clinical status on a given study day. A score of 1 indicates the patient is not hospitalized and has no limitations on activities. A score of 8 indicates the patient has died.	Day 28 and Day 60
Secondary	Time to Disease Progression Based on NIAID Score	Time to progression of disease as determined by a = 2-point increase in the NIAID ordinal scale up to Day 28, and Day 60. The NIAID ordinal scale is a 1-8 scale and is an assessment of clinical status on a given study day. A score of 1 indicates the patient is not hospitalized and has no limitations on activities. A score of 8 indicates the patient has died.	Day 28 and Day 60
Secondary	Change From Baseline in Overall Symptom Scores	Change from baseline in overall symptom score as measured by the Symptom Score Questionnaire on Day 7, Day 14 and Day 28. The overall symptom score is the sum of 14 individual symptom scores from Symptom Score Questionnaire. Individual symptom scores correspond to the following responses: None = 0, Mild = 1, Moderate = 2, Severe = 3; None = 0, 1-2 times = 1, 3-4 times = 2, 5 or more times = 3; Same as usual = 0, Less than usual = 1, No sense = 2. The lowest score could be 0, and the highest score could be 42. Patients with higher scores have more severe symptoms from COVID-19.	Day 7, 14, and 28
Secondary	Number of Participants With Adverse Events	Adverse events up to Day 60	60 days