Clinical trial NCT04449588: Efficacy and Safety Study of BDB-001 in Severe COVID-19 With ALI/ARDS
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: COVID-19 Pneumonia
Keywords: COVID-19
Severe Pneumonia
ALI/ARDS
Lead sponsor: Staidson (Beijing) Biopharmaceuticals Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Beijing Defengrui Biotechnology Co. Ltd
First posted: 2020-06-29
Enrollment: 369
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Time to recovery of peripheral capillary oxygen saturation (SpO2) from baseline
timeFrame: Baseline to Day 28
Secondary outcomes:
measure: 28-day all-cause mortality rate
timeFrame: Baseline to Day 28
measure: Percentage of patients who progress to critical severe
timeFrame: Baseline to Day 28
measure: Percentage of subjects achieving recovery in SpO2
timeFrame: Baseline to Day 28
measure: Mean change of PaO2/FiO2
timeFrame: Baseline to Day 28
measure: Mechanical ventilation time
timeFrame: Baseline to Day 28
measure: Time of oxygen therapy
timeFrame: Baseline to Day 28
measure: Change in inflammation indicators (CRP or IL-6 etc.) from baseline
timeFrame: Baseline to Day 28
measure: Improvement in body temperature
timeFrame: Baseline to Day 28
measure: Mean change from baseline in the clinical improvement based on ordinal scale recommended by the WHO R&D Blueprint during treatment period
timeFrame: Baseline to Day 28
measure: Improvement at D3, 7, 11 & D14 based on ordinal scale recommended by the WHO R&D Blueprint during treatment period
timeFrame: Baseline，Day 3，Day 7，Day 11，Day 14
measure: Time to get categories 1 to 4 in the 8-points ordinal scale
timeFrame: Baseline to Day 28
measure: Time to attain an improvement of 1 point on the ordinal scale
timeFrame: Baseline to Day 28
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Asgar Ali Hospital
city: Dhaka
country: Bangladesh
facility: Bangladesh Specialized Hospital
city: Chongqing
country: China
facility: Southwest Hospital Chongqing
state: Chongqing
city: Nagpur
country: India
facility: Noble Hospital Pvt Ltd
city: Pune
country: India
facility: Government Medical College and Hospital
city: Jakarta
country: Indonesia
facility: RSUD Cengkareng(Cengkareng General Hospital)
state: Jakrata
city: Jakarta
country: Indonesia
facility: RSUD Pasar Minggu(Pasar Minggu General Hospital)
city: Jakarta
country: Indonesia
facility: RSUP Persahabatan(Persahabatan General Hospital)
city: Madrid
country: Spain
facility: Hospital Universitario 12 De Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Díaz
Study officials:
affiliation: Southwest Hospital of Chongqing
name: Qing Mao, Ph.D
role: PRINCIPAL_INVESTIGATOR
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citation: Wang R, Xiao H, Guo R, Li Y, Shen B. The role of C5a in acute lung injury induced by highly pathogenic viral infections. Emerg Microbes Infect. 2015 May;4(5):e28. doi: 10.1038/emi.2015.28. Epub 2015 May 6.
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