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

NCT06693362 | Recruiting Phase 1 DMC

• 2 other identifiers: ZJSCHZ-SC01009-01CTR20243748
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Severe Viral Pneumonia(Not Include COVID-19)

Keywords

severe pneumonia; Safety and Efficacy; Uterine blood mesenchymal stem cells; cell therapy; Phase I clinical trial

Outcome Measures

Primary Outcomes (7)

• Incidence of AE/SAE

  Incidence of adverse events/serious adverse events

  from the time of medication on day 1 until 24 weeks ± 7 days after discharge, an average of 2 years.

• Infusion reactions

  Infusion reactions (including fever, rigors, itching, hypotension, dyspnea, chest discomfort, rash, urticaria, angioedema, wheezing, tachycardia, and allergic reactions) during the administration period (approximately 2 hours) and within 8 hours after the completion of the infusion, including the time period from the first dose (start of infusion) to 8 hours after the last dose (given on alternate days for a total of 3 times)

  On days D1, D3, and D5, during the infusion and within 8 hours after the completion of the infusion, an average of 10 hours

• Inflammatory markers

  White Blood Cell count (WBC), Neutrophil percentage (N%), C-reactive protein (CRP), Procalcitonin (PCT), Interleukin-6 (IL-6), IL-8, IL-10, Tumor Necrosis Factor-alpha (TNF-α), Interferon-alpha (IFN-α), Interferon-gamma (IFN-γ) will be combined as the "Inflammatory markers".

  from the time of patient infusion to discharge，an average of 3 months

• Immune markers

  Immune markers from the time of patient infusion to discharge: Absolute count of CD3, Absolute count of CD4, Absolute count of CD8, CD4+/CD8+ ratio.

  from the time of patient infusion to discharge, an average of 3 months

• Mortality

  The all-cause mortality rate within 28 days after enrollment (the ratio of the total number of deaths from all causes to the total number of subjects).

  28 days

• Pneumonia improvement time

  The time required for improvement of severe pneumonia after enrollment.

  28 days

• Pneumonia improvement rate

  The improvement rate of pneumonia within 28 days after enrollment

  28 days

Secondary Outcomes (9)

• Hospital stay

  starting from the day a patient is enrolled in a study or treatment protocol and continues until the day of their discharge from the hospital, an average of 3 months.

• ICU stay

  the period commencing from the day a patient is enrolled in a clinical study or treatment protocol and ending on the day the patient is discharged from the intensive care unit (ICU), assessed up to 3 months

• All-cause mortality

  8 weeks

• viral pneumonia improvement

  28 days

• ARDS incidence rate

  From the time the patient enters the study until they discharge due to death or other reasons，an average of 3 months.

Study Arms (2)

The Control Group

PLACEBO COMPARATOR

Received SC01009 placebo plus standard treatment

Drug: Placebo; Other: Standard Treatment

The Treatment Group

EXPERIMENTAL

Received SC01009 in addition to standard treatment.

Drug: Drug therapy; Other: Standard Treatment

Interventions

Placebo DRUG

The Menstrual blood derived mesenchymal stem cells（Men-MSCs）Placebo is administered via intravenous infusion, divided into 3 separate infusions, conducted on alternate days (i.e., Day 1, Day 3, and Day 5).The placebo must be thawed, and 3 vials of placebo must be diluted into 500ml of compound electrolyte injection solution. The medication is administered via intravenous infusion, starting with a slow drip for the first 15 minutes (30-40 drops per minute), and completed within 120 minutes to ensure cell viability. During the infusion process, the infusion bag can be gently shaken appropriately to ensure even suspension of the cells.

The Control Group

Drug therapy DRUG

The Menstrual blood derived mesenchymal stem cells（Men-MSCs) injection (SC01009) is administered via intravenous infusion, with a total dose of 9×10\^7 cells, divided into 3 separate infusions, conducted on alternate days (i.e., Day 1, Day 3, and Day 5), with each infusion consisting of 3×10\^7 cells.Before the infusion, SC01009 injection must be thawed, and 3 vials of SC01009 must be diluted into 500ml of compound electrolyte injection solution. The medication is administered via intravenous infusion, starting with a slow drip for the first 15 minutes (30-40 drops per minute), and completed within 120 minutes to ensure cell viability. During the infusion process, the infusion bag can be gently shaken appropriately to ensure even suspension of the cells.

The Treatment Group

Standard Treatment OTHER

Anti-infective and anti-inflammatory drugs: For hospitalized patients with CAP, it is recommended to use β-lactams alone or in combination with doxycycline, minocycline, macrolides, or respiratory quinolones alone. Corticosteroids: For patients with septic shock, hydrocortisone hemisuccinate 200 mg/day is recommended. The medication should be discontinued promptly after the correction of septic shock, and the duration of use should generally not exceed 7 days. Antiviral drugs: Oseltamivir, acyclovir, etc. Antipyretic drugs for those with high fever: such as aspirin, acetaminophen, indomethacin, sulindac, naproxen, etc. Cough and expectorant drugs for cough and phlegm: ambroxol hydrochloride, acetylcysteine tablets, bromhexine, nacetylethylenediamine, pentedonate, etc. Low molecular weight heparin: For elderly hospitalized CAP patients, the risk of deep vein thrombosis should be assessed, and low molecular weight heparin should be applied for prevention when necessary.

The Control Group; The Treatment Group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged between 18 and 85 years, regardless of gender;
• 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.)
• 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;
• Compliance with the policies and institutional arrangements for pathogen control by the Health Commission of the region (country) where the experimental center is located;
• Voluntarily sign and provide written informed consent.

You may not qualify if:

• 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";
• Severe pneumonia of unknown viral infection, i.e., the viral pathogen infecting the patient is not well documented and recognized in current literature;
• History of cancer or clinical examination confirming premalignant lesions at screening;
• Use of extracorporeal membrane oxygenation (ECMO) at screening;
• History of acute cerebral infarction within 3 months before screening, or history of deep vein thrombosis or pulmonary embolism at screening;
• 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;
• 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;
• 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;
• Severe dysfunction of the liver and kidneys;
• History of poorly controlled mental illness;
• Known or suspected allergy to the active or inactive ingredients of the study medication;
• Pregnant or breastfeeding women and women of childbearing age who are not sterilized/refuse to use medically accepted effective contraception during the study period;
• Men who are not sterilized/refuse to use medically accepted effective contraception during the study period;
• Those who have participated in other clinical trials (excluding those who have not taken medication) or who have previously received stem cell therapy;
• Other circumstances deemed unsuitable for enrollment by the investigator.

Sponsors & Collaborators

• Ruijin Hospital: lead
• Shulan (Hangzhou) Hospital: collaborator
• Shulan(Quzhou) Hospital: collaborator
• West China Hospital: collaborator
• Zhejiang University: collaborator
• The First Affiliated Hospital of Guangzhou Medical University: collaborator
• Shanghai Zhongshan Hospital: collaborator
• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: collaborator
• Henan Provincial People's Hospital: collaborator
• The First Affiliated Hospital of Nanchang University: collaborator

Study Sites (1)

Ruijin Hospital affiliated to Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, China

RECRUITING

MeSH Terms

Conditions

Pneumonia

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Qu Jieming

CONTACT

18901661180; jmqu0906@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2024
• First Posted: November 18, 2024
• Study Start: January 20, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2028
• Last Updated: December 27, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)