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.

Study Overview

• Status: Terminated
• Conditions: Covid19
• Intervention / Treatment: Other: Placebo; Drug: BGE-175

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 194
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1426ABP
      • Clinica Privada Independencia
  • Ciudad Autonoma De Buenos Aires
    • Buenos Aires, Ciudad Autonoma De Buenos Aires, Argentina, C1039AAO
      • Sanatorio de la Trinidad Mitre
  • Ciudad Autónoma De Buenos Aires
    • Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina, C1430EGF
      • Clinica Adventista Belgrano (CAB)
• Brazil
  • Rio De Janeiro, Brazil, 21040-360
    • Instituto Nacional de Infectologia Evandro Chagas / Fundação Oswaldo Cruz (FIOCRUZ)
  • Espiritu Santo
    • Vitória, Espiritu Santo, Brazil, 29043-260
      • Hospital Universitario Cassiano Antonio de Moraes
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30180-080
      • Hospital Felicio Rocho (HFR)
  • Rio Grande Do Sol
    • Santa Cruz Do Sul, Rio Grande Do Sol, Brazil, 96835-090
      • Centro de Pesquisa Hospital Ana Nery Santa Cruz do Sul
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90160-093
      • Hospital Ernesto Dornelles
  • Santa Catarina
    • Chapecó, Santa Catarina, Brazil, 89801-355
      • Clínica Supera Oncologia
  • Sao Paulo
    • Barretos, Sao Paulo, Brazil, 14784-400
      • Unidade de Pesquisa Clinica da Fundação Pio XII - Hospital de Amor de Barretos
    • Botucatu, Sao Paulo, Brazil, 18618-687
      • Hospital das Clínicas da Faculdade de Medicina de Botucatu UNESP (HC-FMB/UNESP)
    • Campinas, Sao Paulo, Brazil, 13060-904
      • Pontificia Universidade Catolica de Campinas (PUC-CAMP) - Hospital e Maternidade Celso Pierro (HMCP) - Centro de Pesquisa São Lucas
    • Sorocaba, Sao Paulo, Brazil, 18040-425
      • Clinica de Alergia Martti Antila
    • São Paulo, Sao Paulo, Brazil, 02432
      • Conjunto Hospitalar de Mandaqui
  • São Paulo
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Fundação Faculdade Regional de Medicina de São José do Rio Preto
• United States
  • Arizona
    • Mesa, Arizona, United States, 85202
      • Banner Health
  • California
    • Chula Vista, California, United States, 91911
      • Velocity Clinical Research, Chula Vista
    • Long Beach, California, United States, 90806
      • Long Beach Medical Center
    • Orange, California, United States, 92868
      • UCI Center for Clinical Research
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
  • Colorado
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
  • Connecticut
    • Stamford, Connecticut, United States, 06904
      • Stamford Hospital
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida - Health, Jacksonville
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health, Lexington
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical System
    • Silver Spring, Maryland, United States, 20904
      • Jadestone Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BGE-175; BGE-175 tablet to be taken by mouth once a day for 14 days	Drug: BGE-175; Drug
Placebo Comparator: Placebo; Placebo tablet to be taken by mouth once a day for 14 days	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Who Have Died or Progressed to Respiratory Failure	Proportion of participants who have died or progressed to respiratory failure as defined by progressing to the need for high-flow nasal cannula O2 delivery, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) at Day 28. The proportion of participants is represented as a percentage.	First dose date up to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Experiencing Treatment-emergent Adverse Events	Proportion of participants experiencing treatment-emergent adverse events as measured by the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0. The proportion of participants is represented as a percentage.	First dose of treatment through study Day 57
Survival	Proportion of participants surviving at Day 14, Day 28, and Day 57. The proportion of participants is represented as a percentage.	Baseline through Day 57; at Day 14, Day 28 and Day 57
Proportion of Subjects Who Survive Without Progression to Respiratory Failure Through Day 28	Proportion of subjects who survive without progression to respiratory failure at Day 28. The proportion of participants is represented as a percentage.	First dose of treatment through Day 14, Day 28
Time to Two Successive Negative Viral Titers in Nasopharyngeal Swabs	Kaplan-Meier Estimate of Time to Two Successive Negative Viral Titers in Nasopharyngeal Swab (median)	Baseline through Day 28
Time to Clinical Worsening From Baseline Value (Defined by Time to ≥ 1-point Worsening on WHO Ordinal Scale for COVID-19)	Kaplan-Meier Estimate of Time to Clinical Worsening from Baseline Value. Time to clinical worsening from baseline value (defined by time to ≥ 1-point worsening on World Health Organization (WHO) Ordinal Scale for COVID-19). The ordinal scale is an assessment of the clinical status at a given day. Each day, the worst score from the previous day will be recorded. The scale is as follows: 0.) Uninfected 1.) Ambulatory with no limitation of activities 2.) Ambulatory with limitation of activities 3.) Hospitalized, mild disease with no oxygen therapy 4.) Hospitalized, mild disease with oxygen by mask or nasal prongs 5.) Hospitalized, severe disease with noninvasive ventilation or high-flow oxygen 6.) Hospitalized, severe disease with intubation and mechanical ventilation 7.) Hospitalized, severe disease with ventilation and additional organ support (pressors, renal retention therapy, extracorporeal membrane oxygenation) 8.) Death. A higher score means a worse outcome.	First dose date up to Day 57
Proportion of Patients Who Develop Critical COVID-19 Illness	Proportion of patients who develop critical COVID-19 illness as defined by at least one of the following: A. RF defined based on resource utilization requiring at least one of the following: Endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates > 20 L/min with fraction of delivered oxygen ≥ 0.5), noninvasive positive pressure ventilation, ECMO, clinical diagnosis respiratory failure (i.e., clinical need for one of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation) B. Hemodynamic compromise (defined by systolic blood pressure < 90 mm Hg, or diastolic blood pressure < 60 mm Hg or requiring vasopressors) C. Multi-organ dysfunction/failure The proportion of participants is represented as a percentage.	First dose date up to Day 57
Time to Clinical Improvement From Baseline Value (Defined by Time to ≥ 1-point Improvement on WHO Ordinal Scale for COVID-19 Score - Must be Maintained Through Day 28)	Kaplan-Meier Estimate of Time to Clinical Improvement from Baseline Value. Time to clinical improvement defined by time to ≥ 1-point improvement on World Health Organization (WHO) Ordinal Scale for COVID-19 - must be maintained through Day 28. The ordinal scale is an assessment of the clinical status at a given day. Each day, the worst score from the previous day will be recorded. The scale is as follows: 0.) Uninfected 1.) Ambulatory with no limitation of activities 2.) Ambulatory with limitation of activities 3.) Hospitalized, mild disease with no oxygen therapy 4.) Hospitalized, mild disease with oxygen by mask or nasal prongs 5.) Hospitalized, severe disease with noninvasive ventilation or high-flow oxygen 6.) Hospitalized, severe disease with intubation and mechanical ventilation 7.) Hospitalized, severe disease with ventilation and additional organ support (pressors, renal retention therapy, extracorporeal membrane oxygenation) 8.) Death. A higher score means a worse outcome.	First dose date up to Day 28
Mean Change From Baseline in WHO Ordinal Scale for COVID-19 Score	Mean change from baseline in WHO Ordinal Scale for COVID-19 score World Health Organization (WHO) Ordinal Scale for COVID-19. The ordinal scale is an assessment of the clinical status at a given day. Each day, the worst score from the previous day will be recorded. The scale is as follows: 0.) Uninfected 1.) Ambulatory with no limitation of activities 2.) Ambulatory with limitation of activities 3.) Hospitalized, mild disease with no oxygen therapy 4.) Hospitalized, mild disease with oxygen by mask or nasal prongs 5.) Hospitalized, severe disease with noninvasive ventilation or high-flow oxygen 6.) Hospitalized, severe disease with intubation and mechanical ventilation 7.) Hospitalized, severe disease with ventilation and additional organ support (pressors, renal retention therapy, extracorporeal membrane oxygenation) 8.) Death. A higher score means a worse outcome.	Day 14/End of Treatment, Day 28, Day 57
Number of Patients Who Had Intubation During the Study	Proportion of Patients who had Intubation during the study defined as proportion of patients who had any documented intubation during the study.	First dose date up to Day 57
Duration of Intubation	Duration of Intubation (first post-dosing intubation)	First dose date up to Day 57
Time to Discharge From Hospital Intensive Care Unit	Time from intensive care unit admission to the recorded time of intensive care unit discharge	First dose date up to Day 57
Number of Patients Who Had Supplemental Oxygen Administration	Proportion of patients who had any documented post-dosing supplemental O2 administration during the study.	First dose date up to Day 57
Duration of Supplemental Oxygen Administration	Duration of participants receiving supplemental oxygen	First dose date up to Day 57
Number of Patients Who Had Noninvasive Ventilation or High-flow Nasal Cannula O2 Administration	Proportion of patients who had any documented post-dosing noninvasive ventilation or high-flow nasal cannula O2 administration.	First dose date up to Day 57
Duration of Noninvasive Ventilation by Nonrebreather Mask or High-flow Nasal Cannula	Duration of participants receiving noninvasive ventilation by nonrebreather mask or high-flow nasal cannula	First dose date up to Day 57
Number of Patients Who Had Mechanical Ventilation.	Proportion of patients who had any documented post-dosing mechanical ventilation.	First dose date up to Day 57
Duration of Mechanical Ventilation	Duration of participants receiving mechanical ventilation	First dose date up to Day 57
Number of Patients Who Had Mechanical Ventilation Plus Additional Organ Support Using Vasopressors, and/or Renal Replacement Therapy and/or ECMO.	Proportion of patients who had any documented post-dosing mechanical ventilation plus additional organ support using vasopressors, and/or renal replacement therapy and/or ECMO.	First dose date up to Day 57
Duration of Mechanical Ventilation Plus Additional Organ Support Using Vasopressors, and/or Renal Replacement Therapy and/or ECMO	Duration of participants receiving mechanical ventilation plus additional organ support using vasopressors, and/or renal replacement therapy and/or ECMO	First dose date up to Day 57
Daily Ratio of Oxygen Saturation (SpO2) to Fractional Inspired O2 (SpO2/FiO2)	Daily ratio of participants' oxygen saturation (SpO2) to fractional inspired O2 (SpO2/FiO2)	First dose date up to Day 28
Time to Discharge From the Hospital	Length (in days) of the time of hospitalization until medical discharge	First dose date up to Day 57
Number of Patients With Re-hospitalization	Proportion of patients who are hospitalized again after the discharge of first hospitalization.	First dose date up to Day 57
Proportion of Participants Requiring Intensive Care Unit Admission	Proportion of participants admitted to hospital intensive care unit post randomization. The proportion of participants is represented as a percentage.	First dose date up to Day 57

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of Inflammation Markers	Inflammation marker IL-6	Day 28
Measure of Inflammation Markers	Inflammation marker CRP	Day 28
Measure of Inflammation Markers	Inflammation marker IL-10	Day 28
Measure of Inflammation Markers	Inflammation marker TNF-α	Day 28
Measure of Inflammation Markers	Inflammation marker IFN-γ	Day 28
Measure of Inflammation Markers	Inflammation marker IFN-α	Day 28
Measure of Inflammation Markers	Inflammation marker IP-10	Day 28
Measure of Inflammation Markers	Inflammation marker MCP-1	Day 28
Measure of Inflammation Markers	Inflammation marker CD4+ T cells	Day 28
Measure of Inflammation Markers	Inflammation marker CD8+ T cells	Day 28
Measure of Inflammation Markers	Absolute lymphocyte count	Day 28
Concentration of BGE-175	Assess peak and trough concentrations of BGE-175 at steady-state	Day 14
Activity of prostaglandin D2	Assess prostaglandin D2 pre-diagnostic to assess correlation with response to treatment for COVID-19 based on change in the WHO Ordinal Scale for COVID-19 score	Day 1
Proportion of participants experiencing any treatment-emergent adverse events	Proportion of participants experiencing any treatment-emergent adverse events as measured by the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0	First dose date up to Day 57
Proportion of participants experiencing any adverse events	Proportion of participants experiencing any adverse events as measured by the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0	First dose date up to Day 57
Proportion of participants experiencing any treatment-emergent graded laboratory abnormalities	Proportion of participants experiencing any treatment-emergent graded laboratory abnormalities as defined by laboratory parameters/reference ranges	First dose date up to Day 57

Collaborators and Investigators

• Sponsor: BioAge Labs, Inc.
• Investigators: Principal Investigator: Richard G Wilkerson, MD, University of Maryland Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2021
• Primary Completion (Actual): April 20, 2022
• Study Completion (Actual): May 19, 2022

Study Registration Dates

• First Submitted: January 4, 2021
• First Submitted That Met QC Criteria: January 8, 2021
• First Posted (Actual): January 12, 2021

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 29, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; Respiratory failure; BioAge; BGE-175
• 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; COVID-19
• Other Study ID Numbers: BGE-175-201

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