A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Evaluate the Safety and Efficacy of Uterine Blood Mesenchymal Stem Cells Injection for the Treatment of Severe Pneumonia Caused by Viruses

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Evaluate the Safety and Efficacy of Uterine Blood Mesenchymal Stem Cells (SC01009) Injection for the Treatment of Severe Pneumonia Caused by Viruses

This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of Menstrual blood-derived Mesenchymal Stem Cells (SC01009) injection for the treatment of severe pneumonia caused by viruses. The purpose of the study is to assess the safety and efficacy of SC01009 injection in combination with standard treatment in patients with severe pneumonia caused by viruses. Viral pneumonia refers to acute inflammation of the lung parenchyma and/or interstitium caused by viral infections, which often leads to varying degrees of hypoxia and infection symptoms in the body, typically manifesting as fever, cough, wheezing, shortness of breath, and moist rales in the lungs, along with abnormalities in chest imaging [such as X-rays, computed tomography (CT), etc.]. Viral severe pneumonia is aggressive in onset, initially presenting with fever, cough, and rhinorrhea; it then rapidly progresses to severe toxic symptoms, with respiratory manifestations including cough and dyspnea, producing white mucoid sputum, purulent sputum, or pink frothy sputum. Severely ill patients are often in a critical state of life, endangering the patient's circulatory system and being in a state of respiratory failure requiring ventilator support. Active treatment of viral severe pneumonia, with appropriate measures, can lead to complete recovery of pulmonary function. If respiratory failure or poor circulatory function occurs and ultimately cannot be corrected, the prognosis is poor. Viral severe pneumonia follows clinical pathways (antiviral treatment guidelines and antiviral drug instructions) for antiviral treatment and appropriate adjunctive therapy. Mesenchymal stem cells (MSCs) are a type of multipotent stem cell with the potential for self-renewal and differentiation, characterized by self-renewal, multilineage differentiation, low immunogenicity, and paracrine functions, capable of homing to damaged areas, promoting epithelial tissue repair, suppressing inflammation, and inhibiting abnormal proliferation of fibroblasts.

SC01009 injection is a cellular therapy product developed by Zhejiang Shengchuang Precision Medical Technology Co., Ltd., with its active ingredient being Menstrual blood-derived Mesenchymal Stem Cells (Men-MSCs). Men-MSCs are derived from allogeneic endometrial tissue of women, and preclinical studies have shown that SC01009 is safe and effective in animals, supporting further clinical development.

Severe Pneumonia Caused by Viruses: This includes, but is not limited to, severe pneumonia caused by infections such as respiratory syncytial virus, influenza virus, rhinovirus, human metapneumovirus, adenovirus, etc.; coronavirus is excluded. Diagnostic Criteria: Subjects with pneumonia caused by viral infections. According to the diagnostic criteria for adult community-acquired pneumonia (CAP) in China's 2018 primary care guidelines, a diagnosis of severe pneumonia can be made if one of the following main criteria or at least three secondary criteria are met. Main criteria: ① Need for endotracheal intubation for mechanical ventilation; ② Septic shock requiring vasopressors despite aggressive fluid resuscitation. Secondary criteria: ① Respiratory rate ≥30 breaths/min; ② Oxygenation index ≤250 mmHg (1 mmHg = 0.133 kPa); ③ Multilobar infiltrates; ④ Altered mental status and/or disorientation; ⑤ Blood urea nitrogen ≥7.14 mmol/L; ⑥ Systolic blood pressure <90 mmHg requiring aggressive fluid resuscitation. Viral Detection Methods: The type or subtype of infecting virus is confirmed by nucleic acid testing of patient samples (oropharyngeal swabs, nasopharyngeal swabs, nasopharyngeal aspirates, tracheal aspirates, sputum, and other respiratory specimens, blood samples). Severe pneumonia (SP) is a serious respiratory disease that has emerged globally in recent years, with complex pathogenesis and difficult treatment. Due to different causes, different pathogens, and different situations leading to lung tissue (bronchioles, alveoli, interstitium) inflammation, there are similar or identical pathophysiological processes. When they develop to a certain stage of the disease, they can all worsen and become SP, causing organ dysfunction or even threatening life . SP is associated with high mortality (short-term and long-term) and pulmonary and extrapulmonary complications. Proper diagnosis and early initiation of adequate antimicrobial treatment for patients with severe pneumonia are key to improving the survival rate of critically ill patients. Viral pneumonia is an acute inflammation of the terminal airways, alveolar cavities, and/or interstitium of the lungs caused by viral infections, often resulting from the downward spread of upper respiratory tract infections. It is more common in winter and spring, and can be sporadic, epidemic, or explosive. Viral pneumonia often causes varying degrees of hypoxia and infection symptoms in the body, usually manifesting as fever, cough, wheezing, shortness of breath, and moist rales in the lungs, along with abnormalities in chest imaging [such as X-rays, computed tomography (CT), etc.]. Common pathogens include influenza A virus, parainfluenza virus, adenovirus, coronavirus, coxsackievirus, cytomegalovirus, respiratory syncytial virus, measles virus, varicella virus, etc. The imaging manifestations of viral pneumonia are diverse, but the lesions are often multiple and diffuse, distributed along the periphery and around bronchovascular bundles, with early presentations of multiple small patchy shadows and interstitial changes, thickening of the interlobular and intralobular septa; as the disease worsens, it manifests as multiple ground-glass opacities, which can progress to patchy, nodular, or large confluent consolidations . Typically, viruses from the same virus family have similar pathogenic mechanisms, hence the imaging of viral pneumonia they cause is similar. In terms of pathological characteristics, different severe viral pneumonias also share commonalities . The main manifestations are histological patterns of acute interstitial pneumonia changes, with or without diffuse alveolar damage. Grossly: Lung tissue is enlarged in volume and increased in weight due to congestion and edema (varying with the degree of lesions), with hemorrhagic areas appearing purplish red, and milder lesions may not be apparent. Microscopically: The lesions can be roughly divided into early, middle, late, and terminal stages. Viral severe pneumonia is aggressive in onset, initially presenting with fever, cough, and rhinorrhea; it then rapidly progresses to severe toxic symptoms, with respiratory manifestations including cough and dyspnea, producing white mucoid sputum, purulent sputum, or pink frothy sputum. Wheezing is a significant feature that distinguishes viral pneumonia from bacterial pneumonia, often accompanied by shortness of breath and fever, with severe cases potentially exhibiting lower chest wall inspiratory retractions, perioral cyanosis, and nasal flaring. Physical examination of the lungs often reveals fine to medium moist rales and expiratory wheezing sounds. Chest X-rays may show interstitial infiltrates, patchy shadows, and increased transparency in both lungs, with potential atelectasis. Peripheral blood white blood cell counts are mostly normal, with neutrophil proportions not high, and in cases of bacterial coinfection, white blood cell and neutrophil counts increase. C-reactive protein (CRP) can be normal or slightly elevated. Severely ill patients are often in a critical state of life, endangering the patient's circulatory system, and are in a state of respiratory failure requiring ventilator support. Active treatment of viral severe pneumonia, with appropriate measures, can lead to complete recovery of pulmonary function. If respiratory failure or poor circulatory function occurs and ultimately cannot be corrected, the prognosis is poor. In recent years, new viruses such as the H1N1 influenza virus, H7N9 avian influenza virus, SARS coronavirus (SARS CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) have emerged as new public health issues, leading to outbreaks or epidemics of viral pneumonia on a global or regional scale.

Inclusion Criteria: Patients must meet all of the following criteria to be eligible for this trial:

1. Aged between 18 and 85 years, regardless of gender;
2. Meet the 2018 primary care diagnostic criteria for severe community-acquired pneumonia (CAP) in adults in China; (Diagnosed according to the diagnostic criteria in the "2018 Guidelines for the Diagnosis and Treatment of Community-Acquired Pneumonia in Adults in Primary Care in China." Severe pneumonia can be diagnosed with one of the following major criteria or ≥3 minor criteria. Major criteria: ① Requires endotracheal intubation for mechanical ventilation; ② Septic shock requiring vasoactive medication after aggressive fluid resuscitation. Minor criteria: ① Respiratory rate ≥30 breaths/min; ② Oxygenation index ≤250 mmHg (1 mmHg=0.133 kPa); ③ Multilobar infiltrates; ④ Altered consciousness and/or disorientation; ⑤ Blood urea nitrogen ≥7.14 mmol/L; ⑥ Systolic blood pressure requiring aggressive fluid resuscitation.)
3. Viral infection confirmed by nucleic acid testing from patient specimens (oropharyngeal swabs, nasopharyngeal swabs, nasopharyngeal aspirates, tracheal aspirates, sputum, and other respiratory specimens, blood specimens), excluding SARS-CoV-2;
4. Compliance with the policies and institutional arrangements for pathogen control by the Health Commission of the region (country) where the experimental center is located;
5. Voluntarily sign and provide written informed consent.

Exclusion Criteria: • Patients who meet any of the following criteria are not eligible for this trial:

1. Clearly diagnosed infections caused by non-viral pathogens, including tuberculosis, bacterial pneumonia, mycoplasma pneumonia, chlamydial pneumonia, or other atypical pathogens causing pneumonia, as defined in the "Clinical Laboratory Manual";
2. Severe pneumonia of unknown viral infection, i.e., the viral pathogen infecting the patient is not well documented and recognized in current literature;
3. History of cancer or clinical examination confirming premalignant lesions at screening;
4. Use of extracorporeal membrane oxygenation (ECMO) at screening;
5. History of acute cerebral infarction within 3 months before screening, or history of deep vein thrombosis or pulmonary embolism at screening;
6. Active immunosuppression including: a) Chemotherapy within the last 4 weeks; B) Continuous use of corticosteroid treatment (equivalent to prednisone ≥1mg/kg·d) for nearly 4 weeks; C) Treatment with immunosuppressants (cyclophosphamide, azathioprine, methotrexate, cyclosporin) within 4 weeks; d) Absolute neutrophil count <0.5×10^9/L;
7. Severe cardiovascular disease within 6 months before screening, including unstable heart disease, myocardial infarction, NYHA Class III or IV heart failure, complete left bundle branch block, or second or third degree atrioventricular block;
8. Abnormal and clinically significant test results for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, and syphilis treponemal (syphilis) antibody;
9. Severe dysfunction of the liver and kidneys;
10. History of poorly controlled mental illness;
11. Known or suspected allergy to the active or inactive ingredients of the study medication;
12. Pregnant or breastfeeding women and women of childbearing age who are not sterilized/refuse to use medically accepted effective contraception during the study period;
13. Men who are not sterilized/refuse to use medically accepted effective contraception during the study period;
14. Those who have participated in other clinical trials (excluding those who have not taken medication) or who have previously received stem cell therapy;
15. Other circumstances deemed unsuitable for enrollment by the investigator.