BIO 300 Oral Suspension in Previously Hospitalized Long COVID Patients

Study Overview
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Brief Summary
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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.

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

Conditions
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COVID-19, Long COVID, Pulmonary Fibrosis, Post-acute Respiratory Complications of COVID-19

Intervention / Treatment
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* Drug: BIO 300 Oral Suspension
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 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) Radiographic signs of lung injury after standard treatment of COVID-19 such as, ground glass opacity, consolidation, or fibrotic shadows at screening Able to perform a PFT and have a DLCO <70% of predicted at screening Able to perform a 6-minute walk test Blood routine, liver and kidney function test values are within the controllable range Adequate hepatic function as evidenced by ALT, AST and LDH < 2X ULN and bilirubin < 1.5X ULN for the reference lab 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 Adequate hematopoietic function as evidenced by white blood cells ≥ 3x10^9 / L and platelets ≥ 100x10^9 / L Female patients of childbearing potential must have a negative pregnancy test at screening 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 Ability of the patient or the patient's legal representative to read and provide written informed consent Exclusion Criteria: 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 Severe asthma on chronic therapy with biologics or steroids. 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 D-dimer levels of >2,000 ng/mL at screening 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 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 Use of systemic corticosteroids (e.g., prednisone, dexamethasone) within 5 days of the first scheduled day of study intervention dosing An active infection or infection with a fever ≥ 38.5°C within 3 days of the first scheduled day of study intervention dosing 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 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 Patients taking any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes (www.crediblemeds.org) are not eligible if QTc ≥460 msec Patients who have undergone thoracotomy within 4 weeks of Day 1 of protocol therapy Patients that have a known allergy to any of the placebo components 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 Pregnancy or currently on estrogen-based contraceptives Women who are breastfeeding 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, placebo-controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIO 300 Oral Suspension (genistein 1500 mg)<br>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<br>* Suspension of genistein nanoparticles<br>|
| Placebo Comparator: Placebo<br>BIO 300 Oral Suspension matched placebo will be self-administered daily for 7 days each week for 12 weeks. | Drug: Placebo<br>* Matched placebo for BIO 300 Oral Suspension<br>|

What is the study measuring?
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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 |