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

• Sponsor: BioAge Labs, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04705597
• Collaborator: (none)
• Enrollment: 194
• Locations: 26
• Arms: 2
• Actual Duration (Months): 14.5
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Covid19	Drug: BGE-175; Other: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 194 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Multicenter, Randomized, Double-blind, Placebo-controlledMulticenter, Randomized, Double-blind, Placebo-controlled
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double-blind
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 18, 2021
• Actual Primary Completion Date: Mar 24, 2022
• Actual Study Completion Date: Jun 3, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Proportion of participants who have died or progressed to respiratory failure [First dose date up to Day 28]

   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.

Secondary Outcome Measures

1. Proportion of participants experiencing treatment-emergent adverse events [Day 57]

   Proportion of participants experiencing treatment-emergent adverse events as measured by the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0

2. Survival [Day 14, Day 28, Day 57]

   Proportion of participants surviving at

3. Proportion of subjects who survive without progression to respiratory failure [Day 14, Day 28, Day 57]

   Proportion of subjects who survive without progression to respiratory failure

4. Viral load [Day 28]

   Time to two successive negative viral titers in nasopharyngeal swab

5. Clinical worsening on a 9-point ordinal scale [First dose date up to Day 57]

   Time to clinical worsening from baseline value (defined by time to ≥ 1-point worsening on 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.

6. Clinical improvement [First dose date up to Day 57]

   Defined by time to ≥ 1-point improvement on WHO Ordinal Scale for COVID-19 - must be maintained through Day 28.

7. Clinical improvement [Day 14/End of Treatment, Day 28, Day 57]

   Mean change from baseline in WHO Ordinal Scale for COVID-19 score

8. Time to extubation [First dose date up to Day 57]

   Time from dressing complete to the recorded time of endotracheal tube removal

9. Time to discharge from hospital intensive care unit [First dose date up to Day 57]

   Time from intensive care unit admission to the recorded time of intensive care unit discharge

10. Incidence of supplemental oxygen administration [First dose date up to Day 57]

    Incidence of participants receiving supplemental oxygen

11. Duration of supplemental oxygen administration [First dose date up to Day 57]

    Duration of participants receiving supplemental oxygen

12. Duration of noninvasive ventilation by nonrebreather mask or high-flow nasal cannula [First dose date up to Day 57]

    Duration of participants receiving noninvasive ventilation by nonrebreather mask or high-flow nasal cannula

13. Incidence of noninvasive ventilation by nonrebreather mask or high-flow nasal cannula [First dose date up to Day 57]

    Incidence of participants receiving noninvasive ventilation by nonrebreather mask or high-flow nasal cannula

14. Duration of 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 participants receiving mechanical ventilation plus additional organ support using vasopressors, and/or renal replacement therapy and/or ECMO

15. Incidence of mechanical ventilation plus additional organ support using vasopressors, and/or renal replacement therapy and/or ECMO [First dose date up to Day 57]

    Incidence of participants receiving mechanical ventilation plus additional organ support using vasopressors, and/or renal replacement therapy and/or ECMO

16. Daily ratio of oxygen saturation (SpO2) to fractional inspired O2 (SpO2/FiO2) [First dose date up to Day 28]

    Daily ratio of participants' oxygen saturation (SpO2) to fractional inspired O2 (SpO2/FiO2)

17. Time to discharge from the hospital [First dose date up to Day 57]

    Length (in days) of the time of hospitalization until medical discharge

18. Time to re-hospitalization [First dose date up to Day 57]

    Length (in days) of the time from medical discharge from hospital to rehospitalization

19. Proportion of participants requiring intensive care unit admission [Day 57]

    Proportion of participants admitted to hospital intensive care unit post randomization

Other Outcome Measures

1. Measure of Inflammation Markers [Day 28]

   Inflammation marker IL-6

2. Measure of Inflammation Markers [Day 28]

   Inflammation marker CRP

3. Measure of Inflammation Markers [Day 28]

   Inflammation marker IL-10

4. Measure of Inflammation Markers [Day 28]

   Inflammation marker TNF-α

5. Measure of Inflammation Markers [Day 28]

   Inflammation marker IFN-γ

6. Measure of Inflammation Markers [Day 28]

   Inflammation marker IFN-α

7. Measure of Inflammation Markers [Day 28]

   Inflammation marker IP-10

8. Measure of Inflammation Markers [Day 28]

   Inflammation marker MCP-1

9. Measure of Inflammation Markers [Day 28]

   Inflammation marker CD4+ T cells

10. Measure of Inflammation Markers [Day 28]

    Inflammation marker CD8+ T cells

11. Measure of Inflammation Markers [Day 28]

    Absolute lymphocyte count

12. Concentration of BGE-175 [Day 14]

    Assess peak and trough concentrations of BGE-175 at steady-state

13. Activity of prostaglandin D2 [Day 1]

    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

14. Proportion of participants experiencing any treatment-emergent adverse events [First dose date up to Day 57]

    Proportion of participants experiencing any treatment-emergent adverse events as measured by the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0

15. Proportion of participants experiencing any adverse events [First dose date up to Day 57]

    Proportion of participants experiencing any adverse events as measured by the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0

16. Proportion of participants experiencing any treatment-emergent graded laboratory abnormalities [First dose date up to Day 57]

    Proportion of participants experiencing any treatment-emergent graded laboratory abnormalities as defined by laboratory parameters/reference ranges

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

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

2. 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

Contacts and Locations

Locations

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

Sponsors and Collaborators

• BioAge Labs, Inc.

Investigators

• Principal Investigator: Richard G Wilkerson, MD, University of Maryland Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: BioAge Labs, Inc.
• ClinicalTrials.gov Identifier: NCT04705597
• Other Study ID Numbers: BGE-175-201
• First Posted: Jan 12, 2021
• Last Update Posted: Jun 6, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by BioAge Labs, Inc.: COVID-19; BGE-175; BioAge; Respiratory failure
• Additional relevant MeSH terms: COVID-19

Study Results

No Results Posted as of Jun 6, 2022