BIO 300 Oral Suspension in Previously Hospitalized Long COVID Patients

A Phase 2 Study of BIO 300 Oral Suspension in Discharged COVID-19 Patients

This is a randomized, double-blinded, placebo-controlled, two-arm study to evaluate the safety and efficacy of BIO 300 Oral Suspension (BIO 300) as a therapy to improve lung function in patients that were hospitalized for severe COVID-19-related illness and continue to experience post-acute respiratory complications associated with Long-COVID after discharge. Patients will be randomized 1:1 to receive BIO 300 or placebo.

Study Overview

• Status: Recruiting
• Conditions: COVID-19; Pulmonary Fibrosis; Long COVID; Post-acute Respiratory Complications of COVID-19
• Intervention / Treatment: Drug: BIO 300 Oral Suspension; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael D Kaytor, Ph.D.; Phone Number: 952-400-0405; Email: mkaytor@humaneticscorp.com

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Completed
      • University of Colorado Anschutz Medical Campus
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Contact: Julia Cirillo; Phone Number: 929-455-5970; Email: BIO300@nyulangone.org
      • Principal Investigator: Rany Condos, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas Health Science Center at Houston
      • Sub-Investigator: Bela Patel, MD
      • Contact: MaryJane Keller, NP; Phone Number: 713-486-2012; Email: MaryJane.Keller@uth.tmc.edu
      • Principal Investigator: Isabel Mira-Avendano, MD
      • Sub-Investigator: Rodeo Abrencillo, MD
    • Houston, Texas, United States, 77210
      • Active, not recruiting
      • Houston Methodist Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18
2. Patients hospitalized for COVID-19-related complications ready to be discharged and those within 365 days of discharge (even if the patient was referred to subacute or acute respiratory rehabilitation after discharge)
3. Radiographic signs of lung injury after standard treatment of COVID-19 such as, ground glass opacity, consolidation, or fibrotic shadows at screening
4. Able to perform a PFT and have a DLCO <70% of predicted at screening
5. Able to perform a 6-minute walk test

6. Blood routine, liver and kidney function test values are within the controllable range

   1. Adequate hepatic function as evidenced by ALT, AST and LDH < 2X ULN and bilirubin < 1.5X ULN for the reference lab
   2. Adequate renal function as evidenced by a serum creatinine ≤ 1.5 X ULN for the reference laboratory OR a calculated creatinine clearance of ≥ 60 mL/min by the Cockcroft-Gault Equation
   3. Adequate hematopoietic function as evidenced by white blood cells ≥ 3x10^9 / L and platelets ≥ 100x10^9 / L
7. Female patients of childbearing potential must have a negative pregnancy test at screening
8. Female patients of childbearing potential and male participants with female sexual partners of childbearing potential must agree to use an effective method of non-estrogen-based contraception (e.g., condom and a diaphragm, condom and intrauterine device, condom and Depo-Provera, condom and Nexplanon, or condom and progesterone mini-pill) during the 12-week portion of the study that they are receiving study medication and for 30 days following the last dose of study medication, or to abstain from sexual intercourse during these time periods. Women who have been off estrogen contraceptives for a minimum of 5 days prior to the first scheduled day of study intervention dosing are eligible. A woman not of childbearing potential is one who has undergone bilateral oophorectomies or who is post-menopausal, defined as no menstrual periods for 12 consecutive months
9. Ability of the patient or the patient's legal representative to read and provide written informed consent

Exclusion Criteria:

1. Severe background disease like severe cardiac or pulmonary insufficiency (WHO grade III or IV), severe liver and kidney diseases, severe COPD, severe neurological disease, or concurrent malignancy (other than non-melanoma skin cancer) which is uncontrolled or actively being treated
2. Severe asthma on chronic therapy with biologics or steroids.
3. Prior malignancy in which any thoracic radiotherapy was administered except for partial or tangent breast irradiation for early-stage (stages I or II) breast cancer
4. D-dimer levels of >2,000 ng/mL at screening
5. Use of anti-pulmonary fibrosis drugs (e.g., imatinib, nintedanib, pirfenidone, penicillamine, colchicine, tumor necrosis factor alpha blocker) within 5 days of the first scheduled day of study intervention dosing
6. Use of anti-cytokine release syndrome drugs (e.g., anakinra, sarilumab, siltuximab, tocilizumab and/or lenzilumab) within 5 days of the first scheduled day of study intervention dosing
7. Use of systemic corticosteroids (e.g., prednisone, dexamethasone) within 5 days of the first scheduled day of study intervention dosing
8. An active infection or infection with a fever ≥ 38.5°C within 3 days of the first scheduled day of study intervention dosing
9. Poorly controlled intercurrent illnesses, such as interstitial lung disease, uncontrolled hypertension; poorly controlled diabetes mellitus; unstable angina, myocardial infarction, acute coronary syndrome or cerebrovascular event within 6 months of Screening; history of congestive heart failure (NYHA Class III or IV); severe valvular heart disease; or poorly controlled cardiac arrhythmias not responding to medical therapy or a pacemaker
10. QTc with Fridericia's correction that is unmeasurable, or ≥480 msec on screening ECG. The average QTc from the screening ECG (completed in triplicate) must be <480 msec for the patient to be eligible for the study
11. Patients taking any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes (www.crediblemeds.org) are not eligible if QTc ≥460 msec
12. Patients who have undergone thoracotomy within 4 weeks of Day 1 of protocol therapy
13. Patients that have a known allergy to any of the placebo components
14. Psychiatric conditions, social situations or substance abuse that precludes the ability of the study participant to cooperate with the requirements of the trial and protocol therapy
15. Pregnancy or currently on estrogen-based contraceptives
16. Women who are breastfeeding
17. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

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: BIO 300 Oral Suspension (genistein 1500 mg); BIO 300 Oral Suspension (genistein 1500 mg) will be self-administered daily for 7 days each week for 12 weeks.	Drug: BIO 300 Oral Suspension; Suspension of genistein nanoparticles
Placebo Comparator: Placebo; BIO 300 Oral Suspension matched placebo will be self-administered daily for 7 days each week for 12 weeks.	Drug: Placebo; Matched placebo for BIO 300 Oral Suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in DLCO	Diffusing capacity of the lungs for carbon monoxide (DLCO)	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 6 Minute Walk Test	6 minute walk test (6MWT)	12 Weeks
Change in FVC	Forced vital capacity (FVC)	12 Weeks, 6 Months and 12 Months
Change in St. George's Respiratory Questionnaire (SGRQ) Scores	Patient reported outcome to measure impact on overall health, daily life, and perceived well-being in patients with impaired pulmonary function. Scores range from 0-100 with higher scores indicating more limitations.	12 Weeks, 6 Months and 12 Months
Change in Pulmonary Fibrosis on HRCT Scan	Evidence of pulmonary fibrosis on high resolution computerized tomography (HRCT) scans of the lungs based on a 4-point Likert scale, where 0 is no evidence of fibrosis and 3 is severe fibrosis	12 Weeks, 6 Months and 12 Months
Incidence of Re-Hospitalization	Incidence of hospitalization after initial discharge and initiating treatment	12 Months
All-Cause Mortality	Mortality at 12 months after initiating treatment	12 Months
Change in FEV1	Forced expiratory volume in one second (FEV1)	12 Weeks, 6 Months and 12 Months
Change in FEV1/FVC Ratio	Ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC)	12 Weeks, 6 Months and 12 Months
Change in 6 Minute Walk Test	6 minute walk test (6MWT)	6 Months and 12 Months
Change in Pulse Oximetry at Rest and During the 6MWT	Oxygen saturation (pulse oximetry) at rest and during the 6 minute walk test (6MWT)	12 Weeks, 6 Months and 12 Months
Change in DLCO	Diffusing capacity of the lungs for carbon monoxide (DLCO)	6 Months and 12 Months
Adverse Events Related to BIO 300 Oral Suspension	Evaluate the safety of BIO 300 Oral Suspension treatment	12 Months
Change in Clinical Laboratory Values	Monitoring of blood serum levels for bilirubin, C-reactive protein (CRP), creatinine, blood urea nitrogen (BUN), cholesterol and triglycerides (all reported as mg/dL)	4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
Change in Clinical Laboratory Values	Monitoring of blood serum levels for troponin T, d-dimer and ferritin (all reported as ng/mL)	4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
Change in Clinical Laboratory Values for Albumin	Monitoring of blood serum levels for albumin (g/dL)	4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
Change in Clinical Laboratory Values for Serum Enzymes	Monitoring of blood serum levels for alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) (all reported as Units/L)	4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
Change in Complete Blood Counts with Differential	Monitoring of white blood cell, red blood cell and platelet counts	4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Supplemental Oxygen Use	Prescribed supplemental oxygen flow rate at night, rest and exertion	12 Weeks, 6 Months and 12 Months
Change in Duration of Supplemental Oxygen Use	Duration of supplemental oxygen use	12 Weeks, 6 Months and 12 Months
Change in Serum Cytokine Expression	Expression levels of serum-derived cytokines (IL-1b, IL-6, IL-8, TNFa, and TGFb1)	4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months

Collaborators and Investigators

• Sponsor: Humanetics Corporation
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2020
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: July 17, 2020
• First Submitted That Met QC Criteria: July 21, 2020
• First Posted (Actual): July 22, 2020

Study Record Updates

• Last Update Posted (Estimated): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Fibrosis; Lung Diseases, Interstitial; Chronic Disease; Post-Infectious Disorders; COVID-19; Pulmonary Fibrosis; Post-Acute COVID-19 Syndrome
• Other Study ID Numbers: CL0105-01; 272201800011C-P00005-9999-1 (U.S. NIH Grant/Contract)

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