Clinical trial NCT04705597: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Covid19
Keywords: COVID-19
BGE-175
BioAge
Respiratory failure
Lead sponsor: BioAge Labs, Inc.
Sponsor class: INDUSTRY
First posted: 2021-01-12
Enrollment: 194
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, Randomized, Double-blind, Placebo-controlled
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Participants Who Have Died or Progressed to Respiratory Failure
timeFrame: First dose date up to Day 28
Secondary outcomes:
measure: Proportion of Participants Experiencing Treatment-emergent Adverse Events
timeFrame: First dose of treatment through study Day 57
measure: Survival
timeFrame: Baseline through Day 57; at Day 14, Day 28 and Day 57
measure: Proportion of Subjects Who Survive Without Progression to Respiratory Failure Through Day 28
timeFrame: First dose of treatment through Day 14, Day 28
measure: Time to Two Successive Negative Viral Titers in Nasopharyngeal Swabs
timeFrame: Baseline through Day 28
measure: Time to Clinical Worsening From Baseline Value (Defined by Time to ≥ 1-point Worsening on WHO Ordinal Scale for COVID-19)
timeFrame: First dose date up to Day 57
measure: Proportion of Patients Who Develop Critical COVID-19 Illness
timeFrame: First dose date up to Day 57
measure: 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)
timeFrame: First dose date up to Day 28
measure: Mean Change From Baseline in WHO Ordinal Scale for COVID-19 Score
timeFrame: Day 14/End of Treatment, Day 28, Day 57
measure: Number of Patients Who Had Intubation During the Study
timeFrame: First dose date up to Day 57
measure: Duration of Intubation
timeFrame: First dose date up to Day 57
measure: Time to Discharge From Hospital Intensive Care Unit
timeFrame: First dose date up to Day 57
measure: Number of Patients Who Had Supplemental Oxygen Administration
timeFrame: First dose date up to Day 57
measure: Duration of Supplemental Oxygen Administration
timeFrame: First dose date up to Day 57
measure: Number of Patients Who Had Noninvasive Ventilation or High-flow Nasal Cannula O2 Administration
timeFrame: First dose date up to Day 57
measure: Duration of Noninvasive Ventilation by Nonrebreather Mask or High-flow Nasal Cannula
timeFrame: First dose date up to Day 57
measure: Number of Patients Who Had Mechanical Ventilation.
timeFrame: First dose date up to Day 57
measure: Duration of Mechanical Ventilation
timeFrame: First dose date up to Day 57
measure: Number of Patients Who Had Mechanical Ventilation Plus Additional Organ Support Using Vasopressors, and/or Renal Replacement Therapy and/or ECMO.
timeFrame: First dose date up to Day 57
measure: Duration of Mechanical Ventilation Plus Additional Organ Support Using Vasopressors, and/or Renal Replacement Therapy and/or ECMO
timeFrame: First dose date up to Day 57
measure: Daily Ratio of Oxygen Saturation (SpO2) to Fractional Inspired O2 (SpO2/FiO2)
timeFrame: First dose date up to Day 28
measure: Time to Discharge From the Hospital
timeFrame: First dose date up to Day 57
measure: Number of Patients With Re-hospitalization
timeFrame: First dose date up to Day 57
measure: Proportion of Participants Requiring Intensive Care Unit Admission
timeFrame: First dose date up to Day 57
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Banner Health
state: Arizona
city: Chula Vista
country: United States
facility: Velocity Clinical Research, Chula Vista
state: California
city: Long Beach
country: United States
facility: Long Beach Medical Center
state: California
city: Orange
country: United States
facility: UCI Center for Clinical Research
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Greeley
country: United States
facility: North Colorado Medical Center
state: Colorado
city: Stamford
country: United States
facility: Stamford Hospital
state: Connecticut
city: Jacksonville
country: United States
facility: University of Florida - Health, Jacksonville
state: Florida
city: Lexington
country: United States
facility: Baptist Health, Lexington
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Medical System
state: Maryland
city: Silver Spring
country: United States
facility: Jadestone Clinical Research, LLC
state: Maryland
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Clinica Privada Independencia
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Sanatorio De La Trinidad Mitre
state: Ciudad Autonoma De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Clinica Adventista Belgrano (CAB)
state: Ciudad Autónoma De Buenos Aires
city: Vitória
country: Brazil
facility: Hospital Universitário Cassiano Antônio de Moraes
state: Espiritu Santo
city: Belo Horizonte
country: Brazil
facility: Hospital Felicio Rocho (HFR)
state: Minas Gerais
city: Santa Cruz Do Sul
country: Brazil
facility: Centro de Pesquisa Hospital Ana Nery Santa Cruz do Sul
state: Rio Grande Do Sol
city: Porto Alegre
country: Brazil
facility: Hospital Ernesto Dornelles
state: Rio Grande Do Sul
city: Chapecó
country: Brazil
facility: Clínica Supera Oncologia
state: Santa Catarina
city: Barretos
country: Brazil
facility: Unidade de Pesquisa Clinica da Fundação Pio XII - Hospital de Amor de Barretos
state: Sao Paulo
city: Botucatu
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Botucatu UNESP (HC-FMB/UNESP)
state: Sao Paulo
city: Campinas
country: Brazil
facility: Pontificia Universidade Catolica de Campinas (PUC-CAMP) - Hospital e Maternidade Celso Pierro (HMCP) - Centro de Pesquisa São Lucas
state: Sao Paulo
city: Sorocaba
country: Brazil
facility: Clinica de Alergia Martti Antila
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Conjunto Hospitalar de Mandaqui
state: Sao Paulo
city: São José do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
state: São Paulo
city: Rio De Janeiro
country: Brazil
facility: Instituto Nacional de Infectologia Evandro Chagas / Fundação Oswaldo Cruz (FIOCRUZ)
Study officials:
affiliation: University of Maryland, Baltimore
name: Richard G Wilkerson, MD
role: PRINCIPAL_INVESTIGATOR
References: