Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05983627 |
| Other study ID # |
QS-ARDS-S1 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
August 30, 2023 |
| Est. completion date |
December 31, 2026 |
Study information
| Verified date |
August 2023 |
| Source |
Asia Cell Therapeutics (Shanghai) Co., Ltd. |
| Contact |
Wenli Liu |
| Phone |
+86 13402137712 |
| Email |
liuwenli[@]xibaozhiliao.cn |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The goal of this clinical trial is to evaluate the safety and tolerability of multiple doses
of human umbilical cord mesenchymal stem cell injection in patients with Mild to Moderate
Acute Respiratory Distress Syndrome (ARDS), and to further explore the efficacy,
pharmacodynamic profile and appropriate dose of administration to provide a basis for the use
of safer and more effective treatments for patients with Mild to Moderate Acute Respiratory
Distress Syndrome (ARDS).
Participants are required to sign an informed consent form and, after undergoing a series of
tests and meeting the protocol's entry and exclusion criteria, are assigned to a dose group
for intravenous infusion of human umbilical cord mesenchymal stem cells. Each subject will
receive three infusions.
Description:
Acute respiratory distress syndrome (ARDS) refers to various pathogenic factors that lead to
excessive activation of the lung or even the whole body inflammatory response, which is
manifested by the destruction of the lung epithelium and vascular endothelium, the decrease
of alveolar clearance, and the occurrence of non-cardiogenic pulmonary edema. According to an
international study involving 29144 patients, 10% of patients in ICU are ARDS patients, 23%
of patients with mechanical ventilation suffer from ARDS, and the case fatality rate of ARDS
ranges from 35% to 46%. At present, the treatment of ARDS includes primary disease treatment,
protective mechanical ventilation and drug therapy, such as systemic infection, trauma,
shock, burn, acute severe pancreatitis and other common causes of ARDS.
It is necessary to control the primary disease and control the systemic uncontrolled
inflammatory response induced by it to prevent and treat ARDS. In the treatment of ARDS, in
addition to actively treating the primary disease, respiratory support technology is the main
treatment mode, which aims to correct intractable hypoxemia, prevent alveolar collapse,
reduce the degree of pulmonary edema, improve the oxygenation index, and reduce respiratory
muscle fatigue. In addition to the above treatment means, effective drug therapeutic
intervention should be carried out early. Reducing ventilator dependence is the key to
improve survival rate. Pharmacotherapy for ARDS includes anti-inflammatory drug therapy (such
as glucocorticoids), antioxidant therapy for N-acetylcysteine, and alveolar surfactant
replacement therapy.
Stem cells are a kind of undifferentiated cells that exist in embryonic or adult tissues and
have the potential of self-renewal replication and multidirectional differentiation.
mesenchymal stem cells (MSCs) are the most widely used stem cells in basic and clinical
research. According to literature reports, MSCs have the ability to migrate to damaged
tissues and repair damaged tissues through their multidirectional differentiation potential
in vivo. Through its paracrine mechanism, MSCs can also improve the local microenvironment,
support and promote the regeneration and differentiation of endogenous stem cells, play an
anti-inflammatory role and regulate immunity. Human umbilical cord is considered medical
waste and the collection of human umbilical cord mesenchymal stem cells is non-invasive, so
there are no medical ethical issues with obtaining hUC-MSCs. Similar to other tissue-derived
MSCs, hUC-MSCs have unique self-renewal ability and multi-differentiation potential, such as
the ability to differentiate into adipose, bone, cartilage, nerve, and liver cells. Clinical
trials of MSCs in the treatment of ARDS have been reported. A single-center, randomized,
double-blind Phase I clinical trial reported the safety of intravenous injection of
allogeneic adipose derived MSCs in the treatment of ARDS, and the results showed that MSCs
were safe and non-tumorigenic. Another multi-center Phase I clinical trial reported the
safety of different doses of MSCs derived from bone marrow in the treatment of ARDS. Based on
this, the Phase II a clinical trial showed that MSCs improved the oxygenation index of ARDS
patients. A case report reported that 2 patients with severe refractory ARDS showed
improvement in respiratory distress, hemodynamic disturbance, and multiple organ failure
after receiving MSCs treatment, which may be related to the reduction of inflammatory markers
in the blood. The development of hUC-MSCs stem cell drugs has important clinical application
value. At present, the human umbilical cord mesenchymal stem cell injection has completed the
pharmacodynamics test of lung injury, the 4-week repeated administration in rats for 8 weeks,
the 4-week repeated administration in rats for 8 weeks, the 4-week repeated administration in
rhesus monkeys for 8 weeks, and the 4-week repeated administration in rhesus monkeys for 8
weeks Week recovery toxicity test, transfer and validation of toxic bioassay method (qPCR
method), in vitro tumorigenesis test (soft AGAR cloning method), in vivo tumorigenesis test
in naked mice (non-GLP), in vitro hemolysis test (rabbit blood), tissue distribution study in
rats, safety pharmacological test of central nervous system in rats. In summary, the
treatment of human umbilical cord mesenchymal stem cells has a wide safety window, and
preclinical studies have shown that this product is safe and effective; The sponsors and
investigators believe that MSC transplantation may improve the clinical symptoms of ARDS.
The clinical trial design of multi-center, single-arm, single administration, dose increment
+ dose extension was mainly adopted in this study. The "3+3" dose increment design was
adopted in 3 preset dose groups, from low-dose group to high-dose group, and 3-6 subjects
were included in each dose group Receive a corresponding dose. After all subjects in each
dose group have completed the 2-week (14-day) DLT safety observation period, it will be up to
the investigator and sponsor to discuss whether to proceed to the next dose group based on
relevant safety data.
Adverse Events (AE) : All adverse medical events that occur after a clinical trial subject
receives the investigational drug, but a clear causal relationship with the investigational
drug may not be inferred. Adverse events can be symptoms, signs, diseases, or abnormalities
in laboratory tests and include the following:
1. An aggravation of the pre-existing (prior to entry into the clinical trial) medical
condition/disease (including an aggravation of symptoms, signs, laboratory
abnormalities).
2. Any newly occurring adverse event: Any newly occurring adverse medical condition
(including symptoms, signs, and newly diagnosed diseases).
3. Abnormal clinically significant laboratory test values or results that are not caused by
concomitant disease.
Adverse reaction (ADR) : Any harmful or unintended reaction that may be associated with the
investigational drug during a clinical trial. There is at least one reasonable possibility of
a causal relationship between the investigational drug product and the adverse reaction, that
is, an association cannot be ruled out.
Adverse events are monitored throughout the trial and it is the responsibility of the
investigator to record all aes observed during the trial. The trial should record any adverse
medical events, regardless of severity and causal relationship with the investigational drug,
from the time of initial dosing until the end of follow-up, and the investigator should
record them on the appropriate AE page in the CRF
