SCOPE: Sargramostim Use in COVID-19 to Recover Patient Health

Sponsor

Partner Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT04707664

Collaborator

United States Department of Defense (U.S. Fed)

600

Enrollment

Locations

Arms

9.2

Actual Duration (Months)

16.2

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Covid19 SARS-CoV Infection	Drug: Sargramostim Drug: Placebo	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

600 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model 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.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.

Masking:

Double (Participant, Investigator)

Masking Description:

Double blind

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 27, 2021

Actual Primary Completion Date :

Dec 28, 2021

Actual Study Completion Date :

Jan 31, 2022

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 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. Other Names: Leukine GM-CSF
Placebo Comparator: Placebo Arm Day 1 - 5: Placebo treatment in addition to standard of care for COVID-19	Drug: 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.

Arm

Intervention/Treatment

Experimental: Sargramostim Arm

Day 1 - 5: Sargramostim treatment in addition to standard of care for COVID-19

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.

Other Names:

Leukine

GM-CSF

Placebo Comparator: Placebo Arm

Day 1 - 5: Placebo treatment in addition to standard of care for COVID-19

Drug: 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.

Outcome Measures

Primary Outcome Measures

Any emergency room visit or hospitalization, or death [28 days]
Proportion of patients who experience any emergency room visit or hospitalization, or death

Secondary Outcome Measures

Disease Progression based on NIAID Score [28, 60 days]
Proportion of patients with any progression of disease as determined by a ≥ 2-point increase from baseline in the NIAID ordinal scale up to Day 28, and Day 60
Time to Disease Progression based on NIAID Score [28, 60 days]
Time to progression of disease as determined by a ≥ 2-point increase in the NIAID ordinal scale up to Day 28, and Day 60
Change from Baseline in Symptom Scores [28 days]
Change from baseline in overall symptom score, and individual symptom scores, as measured by the Symptom Score Questionnaire up to Day 28
Adverse Events [60 days]
Adverse events up to Day 60

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
Have one or more of the following mild or moderate COVID-19 symptoms for ≤5 days prior to randomization:
Fever or chills
New onset or worsening cough
Sore throat
Malaise or fatigue
Headache
Muscle pain (myalgias) or body aches
Gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea)
New onset or worsening shortness of breath or difficulty breathing
Nasal congestion or runny nose
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.
At higher risk for progression to more severe COVID-19
Age ≥ 60 years
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

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
Negative pregnancy test (if woman of childbearing potential)
Females of childbearing potential and males with female partners of childbearing potential must agree to use acceptable contraceptive methods from screening to Day 28
The patient (or legally authorized decision maker) must give informed consent

Exclusion Criteria:

Hospitalized patients
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
Patients enrolled in interventional clinical trials for other experimental therapies
Patients on chronic oxygen supplementation due to cardiopulmonary or other conditions
Patients with unstable comorbid conditions (e.g., decompensated congestive heart failure, COPD with exacerbation, current angina pectoris, uncontrolled diabetes mellitus, uncontrolled hypertension, uncontrolled asthma)
Patients with severe pulmonary comorbid conditions, including systemic steroid-dependent asthma, systemic steroid-dependent COPD, oxygen-dependent COPD, lung transplant, or cystic fibrosis
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
Patients with known or suspected intolerance or hypersensitivity to sargramostim, or any component of the product
Patients who have previously experienced severe and unexplained side effects during aerosol delivery of any kind of medical product
Pregnant or breastfeeding females
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	West Valley Research Clinic, LLC	Phoenix	Arizona	United States	85031
2	Applied Research Center of Arkansas	Little Rock	Arkansas	United States	72212
3	Hope Clinical Research	Canoga Park	California	United States	91303
4	Benchmark Research	Colton	California	United States	92324
5	Synergy Healthcare	Bradenton	Florida	United States	34208
6	Invesclinic US, LLC.	Fort Lauderdale	Florida	United States	33308
7	Indago Research & Health Center, Inc. (Subject Visits Only)	Hialeah	Florida	United States	33012
8	Encore Medical Research	Hollywood	Florida	United States	33021
9	IMIC Inc.	Palmetto Bay	Florida	United States	33157
10	Encore Medical Research of Weston	Weston	Florida	United States	33331
11	Gwinnett Research Institute, LLC	Buford	Georgia	United States	30519
12	Paramount Research Solutions	College Park	Georgia	United States	30349
13	TidalHealth Peninsula Regional, Inc.	Salisbury	Maryland	United States	21801
14	Revive Research Institute, Inc.	Farmington Hills	Michigan	United States	48334
15	Revival Research Institute, LLC.	Sterling Heights	Michigan	United States	48312
16	Olive Branch Family Medical Center	Olive Branch	Mississippi	United States	38654
17	Great Plains Health	North Platte	Nebraska	United States	69101
18	Excel Clinical Research	Las Vegas	Nevada	United States	89109
19	Richmond University Medical Center	Staten Island	New York	United States	10310
20	Monroe Biomedical Research	Monroe	North Carolina	United States	28112
21	Hometown Urgent Care and Research	Cincinnati	Ohio	United States	45215
22	Hometown Urgent Care and Research	Columbus	Ohio	United States	43214
23	Urgent Care Specialists, LLC DBA Hometown Urgent Care and Research	Dayton	Ohio	United States	45424
24	TruCare Internal Medicine and Infectious Disease	DuBois	Pennsylvania	United States	15801
25	Urgent Care Clinical Trials @ AFC Urgent Care - Easley	Easley	South Carolina	United States	29640
26	University Diabetes & Endocrine Consuttants	Chattanooga	Tennessee	United States	37411
27	UCCT @ City Doc Urgent Care-McKinney	Dallas	Texas	United States	75204
28	Invesclinic US LLC	Edinburg	Texas	United States	78539
29	Dorrington Medical Associates	Houston	Texas	United States	77030
30	Encore Imaging & Medical Research	Houston	Texas	United States	77065
31	SMS Clinical Research, LLC	Mesquite	Texas	United States	75149
32	Novotrial Research Group	Pearland	Texas	United States	77584
33	Sun Research Institute	San Antonio	Texas	United States	78215
34	University of Utah Health	Salt Lake City	Utah	United States	84108
35	Centro de Investigaciones Medicas Mar del Plata	Mar del Plata	Buenos Aires	Argentina	7600
36	Instituto Medico de la Fundacion Estudios Clinicos	Rosario	Santa Fe	Argentina	2000
37	Sanatorio Santa Barbara	Buenos Aires		Argentina	C1414DTK