Clinical trial NCT04482595: BIO 300 Oral Suspension in Previously Hospitalized Long COVID Patients
Official title: A Phase 2 Study of BIO 300 Oral Suspension in Discharged COVID-19 Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: COVID-19
Long COVID
Pulmonary Fibrosis
Post-acute Respiratory Complications of COVID-19
Lead sponsor: Humanetics Corporation
Sponsor class: INDUSTRY
Collaborators: name: NYU Langone Health
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2020-07-22
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, placebo-controlled
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in DLCO
timeFrame: 12 Weeks
Secondary outcomes:
measure: Change in 6 Minute Walk Test
timeFrame: 12 Weeks
measure: Change in FVC
timeFrame: 12 Weeks, 6 Months and 12 Months
measure: Change in St. George's Respiratory Questionnaire (SGRQ) Scores
timeFrame: 12 Weeks, 6 Months and 12 Months
measure: Change in Pulmonary Fibrosis on HRCT Scan
timeFrame: 12 Weeks, 6 Months and 12 Months
measure: Incidence of Re-Hospitalization
timeFrame: 12 Months
measure: All-Cause Mortality
timeFrame: 12 Months
measure: Change in FEV1
timeFrame: 12 Weeks, 6 Months and 12 Months
measure: Change in FEV1/FVC Ratio
timeFrame: 12 Weeks, 6 Months and 12 Months
measure: Change in 6 Minute Walk Test
timeFrame: 6 Months and 12 Months
measure: Change in Pulse Oximetry at Rest and During the 6MWT
timeFrame: 12 Weeks, 6 Months and 12 Months
measure: Change in DLCO
timeFrame: 6 Months and 12 Months
measure: Adverse Events Related to BIO 300 Oral Suspension
timeFrame: 12 Months
measure: Change in Clinical Laboratory Values
timeFrame: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
measure: Change in Clinical Laboratory Values
timeFrame: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
measure: Change in Clinical Laboratory Values for Albumin
timeFrame: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
measure: Change in Clinical Laboratory Values for Serum Enzymes
timeFrame: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
measure: Change in Complete Blood Counts with Differential
timeFrame: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
Other outcomes:
measure: Change in Supplemental Oxygen Use
timeFrame: 12 Weeks, 6 Months and 12 Months
measure: Change in Duration of Supplemental Oxygen Use
timeFrame: 12 Weeks, 6 Months and 12 Months
measure: Change in Serum Cytokine Expression
timeFrame: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: Houston Methodist Research Institute
state: Texas
Study officials:
References: