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).

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Drug: BDB-001 Injection; Other: Conventional treatment

• Study Type: Interventional
• Enrollment (Estimated): 368
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Du Zhouqi; Phone Number: +86 17600505723; Email: duzhouqi@staidson.com

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • Asgar Ali Hospital
  • Dhaka, Bangladesh
    • Bangladesh Specialized Hospital
• China
  • Chongqing
    • Chongqing, Chongqing, China, 400038
      • Southwest Hospital Chongqing
• India
  • Nagpur, India
    • Noble Hospital Pvt Ltd
  • Pune, India
    • Government Medical College and Hospital
• Indonesia
  • Jakarta, Indonesia, 12550
    • RSUD Pasar Minggu(Pasar Minggu General Hospital)
  • Jakarta, Indonesia, 13230
    • RSUP Persahabatan(Persahabatan General Hospital)
  • Jakrata
    • Jakarta, Jakrata, Indonesia, 11730
      • RSUD Cengkareng(Cengkareng General Hospital)
• Spain
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Hospital Universitario Clinico San Carlos
  • Madrid, Spain
    • Hospital Universitario de La Princesa
  • Madrid, Spain
    • Hospital Universitario Fundación Díaz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Staidson (Beijing) Biopharmaceuticals Co., Ltd
• Collaborators: Beijing Defengrui Biotechnology Co. Ltd
• Investigators: Principal Investigator: Qing Mao, Ph.D, Southwest Hospital of Chongqing

Publications and helpful links

General Publications

• 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.
• Guo RF, Ward PA. Role of C5a in inflammatory responses. Annu Rev Immunol. 2005;23:821-52. doi: 10.1146/annurev.immunol.23.021704.115835.
• Wood AJT, Vassallo A, Summers C, Chilvers ER, Conway-Morris A. C5a anaphylatoxin and its role in critical illness-induced organ dysfunction. Eur J Clin Invest. 2018 Dec;48(12):e13028. doi: 10.1111/eci.13028. Epub 2018 Oct 15.
• Sun S, Zhao G, Liu C, Fan W, Zhou X, Zeng L, Guo Y, Kou Z, Yu H, Li J, Wang R, Li Y, Schneider C, Habel M, Riedemann NC, Du L, Jiang S, Guo R, Zhou Y. Treatment with anti-C5a antibody improves the outcome of H7N9 virus infection in African green monkeys. Clin Infect Dis. 2015 Feb 15;60(4):586-95. doi: 10.1093/cid/ciu887. Epub 2014 Nov 27.
• Sun S, Zhao G, Liu C, Wu X, Guo Y, Yu H, Song H, Du L, Jiang S, Guo R, Tomlinson S, Zhou Y. Inhibition of complement activation alleviates acute lung injury induced by highly pathogenic avian influenza H5N1 virus infection. Am J Respir Cell Mol Biol. 2013 Aug;49(2):221-30. doi: 10.1165/rcmb.2012-0428OC.

Helpful Links

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Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2020
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: June 26, 2020
• First Submitted That Met QC Criteria: June 26, 2020
• First Posted (Actual): June 29, 2020

Study Record Updates

• Last Update Posted (Actual): December 29, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; ALI/ARDS; Severe Pneumonia
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia
• Other Study ID Numbers: STS-BDB001-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No