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

Covid19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04705597
• Other study ID #: BGE-175-201
• Status: Terminated
• Phase: Phase 2
• Start date: March 18, 2021
• Est. completion date: May 19, 2022

Study information

• Verified date: June 2023
• Source: BioAge Labs, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 194
• Est. completion date: May 19, 2022
• Est. primary completion date: April 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Drug:
• BGE-175
Drug

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
Argentina	Clinica Adventista Belgrano (CAB)	Buenos Aires	Ciudad Autónoma De Buenos Aires
Argentina	Sanatorio De La Trinidad Mitre	Buenos Aires	Ciudad Autonoma De Buenos Aires
Argentina	Clinica Privada Independencia	Ciudad Autonoma de Buenos Aires	Buenos Aires
Brazil	Unidade de Pesquisa Clinica da Fundação Pio XII - Hospital de Amor de Barretos	Barretos	Sao Paulo
Brazil	Hospital Felicio Rocho (HFR)	Belo Horizonte	Minas Gerais
Brazil	Hospital das Clínicas da Faculdade de Medicina de Botucatu UNESP (HC-FMB/UNESP)	Botucatu	Sao Paulo
Brazil	Pontificia Universidade Catolica de Campinas (PUC-CAMP) - Hospital e Maternidade Celso Pierro (HMCP) - Centro de Pesquisa São Lucas	Campinas	Sao Paulo
Brazil	Clínica Supera Oncologia	Chapecó	Santa Catarina
Brazil	Hospital Ernesto Dornelles	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Nacional de Infectologia Evandro Chagas / Fundação Oswaldo Cruz (FIOCRUZ)	Rio De Janeiro
Brazil	Centro de Pesquisa Hospital Ana Nery Santa Cruz do Sul	Santa Cruz Do Sul	Rio Grande Do Sol
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José do Rio Preto	São Paulo
Brazil	Conjunto Hospitalar de Mandaqui	São Paulo	Sao Paulo
Brazil	Clinica de Alergia Martti Antila	Sorocaba	Sao Paulo
Brazil	Hospital Universitário Cassiano Antônio de Moraes	Vitória	Espiritu Santo
United States	University of Maryland Medical System	Baltimore	Maryland
United States	Velocity Clinical Research, Chula Vista	Chula Vista	California
United States	North Colorado Medical Center	Greeley	Colorado
United States	University of Florida - Health, Jacksonville	Jacksonville	Florida
United States	Baptist Health, Lexington	Lexington	Kentucky
United States	Long Beach Medical Center	Long Beach	California
United States	Banner Health	Mesa	Arizona
United States	UCI Center for Clinical Research	Orange	California
United States	Sharp Memorial Hospital	San Diego	California
United States	Jadestone Clinical Research, LLC	Silver Spring	Maryland
United States	Stamford Hospital	Stamford	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
BioAge Labs, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Duration of Intubation	Duration of Intubation (first post-dosing intubation)	First dose date up to Day 57
Secondary	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
Secondary	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
Secondary	Duration of Supplemental Oxygen Administration	Duration of participants receiving supplemental oxygen	First dose date up to Day 57
Secondary	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
Secondary	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
Secondary	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
Secondary	Duration of Mechanical Ventilation	Duration of participants receiving mechanical ventilation	First dose date up to Day 57
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to Discharge From the Hospital	Length (in days) of the time of hospitalization until medical discharge	First dose date up to Day 57
Secondary	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
Secondary	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