COVID-19, Long COVID, Post-acute Respiratory Complications of COVID-19, Pulmonary Fibrosis
Conditions
Brief summary
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.
Interventions
Suspension of genistein nanoparticles
DRUGPlacebo
Matched placebo for BIO 300 Oral Suspension
Sponsors
NYU Langone Health
National Institute of Allergy and Infectious Diseases (NIAID)
Humanetics Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, placebo-controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in DLCO | 12 Weeks | Diffusing capacity of the lungs for carbon monoxide (DLCO) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in FEV1 | 12 Weeks, 6 Months and 12 Months | Forced expiratory volume in one second (FEV1) |
| Change in Clinical Laboratory Values for Albumin | 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months | Monitoring of blood serum levels for albumin (g/dL) |
| Change in Clinical Laboratory Values for Serum Enzymes | 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months | Monitoring of blood serum levels for alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) (all reported as Units/L) |
| Change in Complete Blood Counts with Differential | 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months | Monitoring of white blood cell, red blood cell and platelet counts |
| Change in 6 Minute Walk Test | 12 Weeks | 6 minute walk test (6MWT) |
| Change in FVC | 12 Weeks, 6 Months and 12 Months | Forced vital capacity (FVC) |
| Change in St. George's Respiratory Questionnaire (SGRQ) Scores | 12 Weeks, 6 Months and 12 Months | 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. |
| Change in Pulmonary Fibrosis on HRCT Scan | 12 Weeks, 6 Months and 12 Months | 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 |
| Incidence of Re-Hospitalization | 12 Months | Incidence of hospitalization after initial discharge and initiating treatment |
| All-Cause Mortality | 12 Months | Mortality at 12 months after initiating treatment |
| Change in FEV1/FVC Ratio | 12 Weeks, 6 Months and 12 Months | Ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) |
| Change in Pulse Oximetry at Rest and During the 6MWT | 12 Weeks, 6 Months and 12 Months | Oxygen saturation (pulse oximetry) at rest and during the 6 minute walk test (6MWT) |
| Change in DLCO | 6 Months and 12 Months | Diffusing capacity of the lungs for carbon monoxide (DLCO) |
| Adverse Events Related to BIO 300 Oral Suspension | 12 Months | Evaluate the safety of BIO 300 Oral Suspension treatment |
| Change in Clinical Laboratory Values | 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months | Monitoring of blood serum levels for bilirubin, C-reactive protein (CRP), creatinine, blood urea nitrogen (BUN), cholesterol and triglycerides (all reported as mg/dL) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Cytokine Expression | 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months | Expression levels of serum-derived cytokines (IL-1b, IL-6, IL-8, TNFa, and TGFb1) |
| Change in Supplemental Oxygen Use | 12 Weeks, 6 Months and 12 Months | Prescribed supplemental oxygen flow rate at night, rest and exertion |
| Change in Duration of Supplemental Oxygen Use | 12 Weeks, 6 Months and 12 Months | Duration of supplemental oxygen use |
Countries
United States
Outcome results
None listed