Study to Evaluate the Safety, Tolerability, and Efficacy of BGE-175 in Hospitalized Adults With Coronavirus Disease 2019 (COVID-19) That Are Not in Respiratory Failure

A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study to Investigate the Efficacy and Safety of BGE-175 in Hospitalized Adults With COVID-19

The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of BGE-175 in participants ≥ 50 years of age hospitalized with documented COVID-19.

This is a randomized, placebo-controlled, parallel-group, multicenter, double-blind study of BGE-175 administered PO or NG in participants ≥ 50 years of age and hospitalized with documented COVID-19 who are not yet in respiratory failure.

After signing informed consent, participants will be screened upon presentation at the hospital. Screening will include full physical examination, vital signs, safety laboratory evaluation, oxygen saturation, pre-diagnostics to measure prostaglandin D2 (PGD2) status, and baseline assessment of World Health Organization (WHO) Ordinal Scale for COVID-19. If confirmed that the participant qualifies for this protocol according to listed inclusion and exclusion criteria, participants will receive the first dose of study medication, PO. The participant will then receive study medication PO or NG (if intubated or unable to swallow medication) once daily, at approximately the same time each day for up to 13 additional days. Study medication will be administered in addition to standard of care deemed appropriate by the treating physician(s). Participants will be randomized to receive BGE-175 or placebo. Participants will be monitored daily for all relevant efficacy outcomes, oxygen saturation, and adverse events. Blood will be drawn periodically for safety laboratory measurements, plasma kinetics, lymphocyte subsets, C-reactive protein, and cytokines. Nasopharyngeal swabs will be collected to measure viral load. Participants will be monitored for 14 days after administration of the last dose (Day 28) and followed through Day 57.

Inclusion Criteria:

• Ability to voluntarily provide informed consent that is documented per local requirements

• An understanding, ability, and willingness to fully comply with study procedures and restrictions

• Hospitalized subjects with a confirmed SARS-CoV-2 infection

• Laboratory (polymerase chain reaction [PCR]) confirmed infection with SARS-CoV-2

• Age ≥ 50 years

• COVID-19 illness of any duration, and oxygen saturation measurements ≤ 94% over 5 minutes on room air (Note: low flow oxygen is permitted, but room air oxygen saturation must be ≤ 94%)

• Not in respiratory failure as defined by at least one of the following:

  1. Respiratory failure defined by requiring at least one of the following:

     • Endotracheal intubation and mechanical ventilation
     • Oxygen delivered by high-flow nasal cannula at flow rates > 20 L/min with fraction of delivered oxygen ≥ 0.5)
     • NIPPV
     • ECMO
     • Clinical diagnosis of respiratory failure (i.e., need for one of the preceding therapies, but preceding therapies are not being administered because it is unavailable in the current setting)

  2. Hemodynamic compromise (defined by systolic blood pressure < 90 mm Hg, or diastolic blood pressure < 60 mm Hg) or requiring vasopressors

  3. Multi-organ dysfunction/failure

• Females subjects of childbearing potential must have a negative pregnancy test at screening or pre-treatment on Day 1

• Male and female subjects of childbearing potential must agree to use methods of contraception that are consistent with local regulations for those participating in clinical studies

Exclusion Criteria:

• Participation in any other randomized, controlled clinical trial of an experimental treatment for COVID-19 (uncontrolled, compassionate use trials are allowed)

• In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments

• Currently participating in a vaccination trial for SARS-CoV-2

• Known positive test for influenza A or influenza B at the time of screening

• Positive for human immunodeficiency virus (HIV) that is not controlled with current treatment

• Hepatitis B surface antigen, or Hepatitis C positive at the time of screening. Subjects who are positive for Hepatitis C but have Hepatitis C virus (HCV) RNA below the limit of quantitation may be enrolled. Subjects with Hepatitis B, but with undetectable viral load, may be enrolled.

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 × the upper limit of normal (ULN)

• Stage 4 severe chronic kidney disease (i.e., estimated glomerular filtration rate [eGFR] < 30 mL/min) or acute renal failure resulting in eGFR < 30 mL/min

• Serious comorbidity, including:

  1. Myocardial infarction (within the last month)
  2. Moderate or severe heart failure (New York Heart Association [NYHA] class III or IV)
  3. Acute stroke (within the last month)
  4. Uncontrolled malignancy. Uncontrolled malignancy would include cancers that are not considered in remission, or solid tumor or hematological malignancies with evidence of disease progression in the past 3 months (i.e., there is evidence of disease progression by Response Evaluation Criteria in Solid Tumours [RECIST] or equivalent relevant criterion for the type of malignancy), and are not considered effectively managed with ongoing treatment as determined by the investigator
  5. Recent severe thromboembolic disease or evidence of severe thromboembolic disease defined as a current large vessel thromboembolic event or a thromboembolic event within the past 3 months (e.g., deep vein thrombosis [DVT], pulmonary embolism, ischemic stroke, transient ischemic attack) requiring interventional treatment. This exclusion does not prohibit prophylaxis for thromboembolic events, including those considered possible with concurrent SARS-CoV-2 infection.

• History of severe allergic or anaphylactic reactions or hypersensitivity to the study drug

• Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive study treatment