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

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

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).

Inclusion Criteria:

1. 18 years old ≤ age ≤ 80 years old, both men or women.

2. 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:

   1. Respiratory distress, RR ≥ 30 times/min
   2. Finger oxygen saturation (SpO2) ≤93% in resting state(room air)
   3. Arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) ≤ 300 mmHg (1 mmHg = 0.133kpa) in supine position
   4. Pulmonary imaging shows lesion progression > 50% within 24-48 hours.

   Symptoms,signs or chest imaging indicates ALI/ARDS;

3. Requiring a mask oxygen therapy,high-flow nasal cannula oxygen therapy(HFNC).

4. The informed consent form signed.

Exclusion Criteria:

Subject who meets any of the following criteria will be excluded from the trial:

1. 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.

2. 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.

3. Subjects on current treatment with a complement inhibitor such as eculizumab within 1 month before randomization.

4. Subjects with hypersensitivity history to any ingredient contained in the drug.

5. 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)

6. Pregnant or lactating woman.

7. Subjects who have participated in other interventional clinical trials in the last 3 months or during this trial.

8. Any other circumstances that the investigator considers inappropriate for the participation in this study.