Efficacy and Safety Study of BDB-001 in Severe COVID-19 With ALI/ARDS

Study Overview
=================
Brief Summary
-----------------
This multi-center, open, randomized study will evaluate the efficacy and safety of BDB-001 injection in severe COVID-19 with severe pneumonia, or acute lung injury/acute respiratory distress syndrome. Patients will be randomized to two treatment arms (Arm A: Conventional treatment + BDB-001; Arm B: Conventional treatment alone).

Official Title
-----------------
A Multi-center, Open-label, Randomized Parallel Controlled Evaluation on the Efficacy and Safety of BDB-001 Injection in the Treatment of Progressive Severe COVID-19 in Phase II/III

Conditions
-----------------
COVID-19 Pneumonia

Intervention / Treatment
-----------------
* Drug: BDB-001 Injection
* Other: Conventional treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years old ≤ age ≤ 80 years old, both men or women. Confirmed SARS-CoV-2 infection, and meet at least one of the following criteria: Confirmed severe COVID-19 in no more than 5 days who meets any of the following criteria: Respiratory distress, RR ≥ 30 times/min Finger oxygen saturation (SpO2) ≤93% in resting state(room air) Arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) ≤ 300 mmHg (1 mmHg = 0.133kpa) in supine position Pulmonary imaging shows lesion progression > 50% within 24-48 hours. Symptoms,signs or chest imaging indicates ALI/ARDS; Requiring a mask oxygen therapy,high-flow nasal cannula oxygen therapy(HFNC). The informed consent form signed. Exclusion Criteria: Subject who meets any of the following criteria will be excluded from the trial: Subjects already progressed into critically severe COVID-19 Critical severe standards refer to FDA guidelines,as shown in Appendix 4 or sepsis and sepsis shock. Concomitant with the following situation:severe lung disease such as chronic obstructive pulmonary disease (moderate to severe type), lung cancers, active tuberculosis; severe cardiovascular and cerebrovascular disease: unstable angina pectoris, myocardial infarction, postcardiac surgery, cardiac function ≥ grade 3 (NYHA Classification), or had undergone heart surgery within 6 months before randomization; severe liver diseases (e.g. Child-Pugh score ≥ grade C); severe kidney diseases, such as renal insufficiency (GFR ≤ 15 mL/min/1.73m^2); immune deficiencies or immune-related diseases : including organ or bone marrow transplantation, some autoimmune diseases, IgG4-related diseases, allergic alveolitis, vasculitis; malignancies. Subjects on current treatment with a complement inhibitor such as eculizumab within 1 month before randomization. Subjects with hypersensitivity history to any ingredient contained in the drug. A subject has used the following drugs within 2 weeks prior to screening procedures: Calcineurin inhibitors (e.g., ciclosporin, tacrolimus, etc.) Proliferation inhibitors (e.g., everolimus, sirolimus, etc.) Anti-metabolic drugs (e.g., mycophenolate mofetil, mycophenolate, purine sulphate, etc.) Recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF)/recombinant human granulocyte colony stimulating factor (rhG-CSF) Pregnant or lactating woman. Subjects who have participated in other interventional clinical trials in the last 3 months or during this trial. Any other circumstances that the investigator considers inappropriate for the participation in this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br> | Drug: BDB-001 Injection<br>* BDB-001 Injection+Conventional treatment<br>|
| Experimental: Control group<br> | Other: Conventional treatment<br>* Conventional treatment only. Local guidelines should be integrated to choose the best supportive care.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recovery of peripheral capillary oxygen saturation (SpO2) from baseline |  | Baseline to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day all-cause mortality rate |  | Baseline to Day 28 | 
| Percentage of patients who progress to critical severe |  | Baseline to Day 28 | 
| Percentage of subjects achieving recovery in SpO2 |  | Baseline to Day 28 | 
| Mean change of PaO2/FiO2 |  | Baseline to Day 28 | 
| Mechanical ventilation time |  | Baseline to Day 28 | 
| Time of oxygen therapy |  | Baseline to Day 28 | 
| Change in inflammation indicators (CRP or IL-6 etc.) from baseline |  | Baseline to Day 28 | 
| Improvement in body temperature |  | Baseline to Day 28 | 
| Mean change from baseline in the clinical improvement based on ordinal scale recommended by the WHO R&D Blueprint during treatment period |  | Baseline to Day 28 | 
| Improvement at D3, 7, 11 & D14 based on ordinal scale recommended by the WHO R&D Blueprint during treatment period |  | Baseline，Day 3，Day 7，Day 11，Day 14 | 
| Time to get categories 1 to 4 in the 8-points ordinal scale |  | Baseline to Day 28 | 
| Time to attain an improvement of 1 point on the ordinal scale |  | Baseline to Day 28 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19, Severe Pneumonia, ALI/ARDS