Clinical trial NCT04707664: Sargramostim Use in COVID-19 to Recover Patient Health
Official title: A Randomized Phase 2b Trial Evaluating Clinical Outcomes of Inhaled Sargramostim in High-risk Patients With Mild-moderate COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
SARS-CoV Infection
Keywords: COVID-19
SARS-CoV2
sargramostim
Leukine
(recombinant human) GM-CSF
immune modulator
SCOPE
Lead sponsor: Partner Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: United States Department of Defense
First posted: 2021-01-13
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With an Emergency Room Visit or Hospitalization, or Death by Day 28
timeFrame: 28 days
Secondary outcomes:
measure: Disease Progression Based on NIAID Score
timeFrame: Day 28 and Day 60
measure: Time to Disease Progression Based on NIAID Score
timeFrame: Day 28 and Day 60
measure: Change From Baseline in Overall Symptom Scores
timeFrame: Day 7, 14, and 28
measure: Number of Participants With Adverse Events
timeFrame: 60 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: West Valley Research Clinic, LLC
state: Arizona
city: Little Rock
country: United States
facility: Applied Research Center of Arkansas
state: Arkansas
city: Canoga Park
country: United States
facility: Hope Clinical Research
state: California
city: Colton
country: United States
facility: Benchmark Research
state: California
city: Bradenton
country: United States
facility: Synergy Healthcare
state: Florida
city: Fort Lauderdale
country: United States
facility: Invesclinic US, LLC.
state: Florida
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc. (Subject Visits Only)
state: Florida
city: Hollywood
country: United States
facility: Encore Medical Research
state: Florida
city: Palmetto Bay
country: United States
facility: IMIC Inc.
state: Florida
city: Weston
country: United States
facility: Encore Medical Research of Weston
state: Florida
city: Buford
country: United States
facility: Gwinnett Research Institute, LLC
state: Georgia
city: College Park
country: United States
facility: Paramount Research Solutions
state: Georgia
city: Salisbury
country: United States
facility: TidalHealth Peninsula Regional, Inc.
state: Maryland
city: Farmington Hills
country: United States
facility: Revive Research Institute, Inc.
state: Michigan
city: Sterling Heights
country: United States
facility: Revival Research Institute, LLC.
state: Michigan
city: Olive Branch
country: United States
facility: Olive Branch Family Medical Center
state: Mississippi
city: North Platte
country: United States
facility: Great Plains Health
state: Nebraska
city: Las Vegas
country: United States
facility: Excel Clinical Research
state: Nevada
city: Staten Island
country: United States
facility: Richmond University Medical Center
state: New York
city: Monroe
country: United States
facility: Monroe Biomedical Research
state: North Carolina
city: Cincinnati
country: United States
facility: Hometown Urgent Care and Research
state: Ohio
city: Columbus
country: United States
facility: Hometown Urgent Care and Research
state: Ohio
city: Dayton
country: United States
facility: Urgent Care Specialists, LLC DBA Hometown Urgent Care and Research
state: Ohio
city: DuBois
country: United States
facility: TruCare Internal Medicine and Infectious Disease
state: Pennsylvania
city: Easley
country: United States
facility: Urgent Care Clinical Trials @ AFC Urgent Care - Easley
state: South Carolina
city: Chattanooga
country: United States
facility: University Diabetes & Endocrine Consultants
state: Tennessee
city: Dallas
country: United States
facility: UCCT @ City Doc Urgent Care-McKinney
state: Texas
city: Edinburg
country: United States
facility: Invesclinic US LLC
state: Texas
city: Houston
country: United States
facility: Dorrington Medical Associates
state: Texas
city: Houston
country: United States
facility: Encore Imaging & Medical Research
state: Texas
city: Mesquite
country: United States
facility: SMS Clinical Research, LLC
state: Texas
city: Pearland
country: United States
facility: Novotrial Research Group
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Mar del Plata
country: Argentina
facility: Centro de Investigaciones Medicas Mar del Plata
state: Buenos Aires
city: Rosario
country: Argentina
facility: Instituto Medico de la Fundacion Estudios Clinicos
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Sanatorio Santa Barbara
Study officials:
affiliation: Partner Therapeutics, Inc.
name: Fiona Garner, PhD
role: STUDY_DIRECTOR
References: