Sargramostim Use in COVID-19 to Recover Patient Health (SCOPE)

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

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.

Study Overview

• Status: Completed
• Conditions: Covid19; SARS-CoV Infection
• Intervention / Treatment: Drug: Sargramostim; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 600
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Number of Participants With Adverse Events	Adverse events up to Day 60	60 days

Collaborators and Investigators

• Sponsor: Partner Therapeutics, Inc.
• Collaborators: United States Department of Defense

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 27, 2021
• Primary Completion (ACTUAL): December 28, 2021
• Study Completion (ACTUAL): January 31, 2022

Study Registration Dates

• First Submitted: January 11, 2021
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (ACTUAL): January 13, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2023
• Last Update Submitted That Met QC Criteria: February 2, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; SARS-CoV2; immune modulator; Leukine; sargramostim; (recombinant human) GM-CSF; SCOPE
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Severe Acute Respiratory Syndrome; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Sargramostim
• Other Study ID Numbers: PTX-001-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No