This study is a single-arm, multiple-dose, dose-escalation, open-label multicenter clinical trial, aiming to evaluate the safety, tolerability, and preliminary efficacy of VUM02 Injection for treatment of idiopathic pulmonary fibrosis (IPF). VUM02 Injection (Human Umbilical Cord Tissue-derived Mesenchymal Stem Cells Injection, hUCT-MSC) is an allogeneic cell therapy product comprising culture-expanded Mesenchymal Stem Cells derived from the human umbilical cord tissue. The product is cryopreserved with the amount of 5 x 10\^7 cells per 10 mL per bag (5 x 10\^6 cells/mL). This study is a multiple-dose tolerability study following the "3+3" dose escalation principle and progressing from the low-dose group to the high-dose group sequentially. Three to six patients will be enrolled in each dose group and administered every 3 days for a total of 3 doses.
This trial includes three predefined dose groups: low dose (5E7 cells/person/time), medium dose (1E8 cells/person/time), and high dose (2E8 cells/person/time) groups, for a multiple-dose tolerability study. Each dose group undergoes an initial safety and tolerability assessment with a single dose. After receiving the initial dose, subjects undergo safety evaluations on Day 3 (including symptom assessment, physical examination, vital signs monitoring, 12-lead electrocardiogram, hematology, urinalysis, blood biochemistry, and coagulation function tests). The decision to proceed with subsequent administrations for subjects who have received the initial dose is made through discussion between the investigator and the sponsor (and/or CRO medical staff) based on safety profiles. This study follows the "3+3" dose escalation principle, progressing from the low-dose group to the high-dose group sequentially. The sample size may be adjusted based on the actual circumstances of the trial, with each subject receiving only one corresponding dose. During the study, a Safety Monitoring Committee (SMC) will be established, consisting of the investigators and representatives from the sponsor. The SMC will review the safety data generated during the study and make decisions regarding dose escalation, modification of escalation doses, alteration of dosing regimens, or study discontinuation. Only after all subjects in the preceding dose group have completed the dose-limiting toxicity (DLT) observation, and the SMC confirms that the dose escalation criteria are met, the enrollment for the next dose group will begin.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
VUM02 Injection will be administered intravenously every 3 days for a total of 3 doses.
Peking University Third Hospital
Beijing, China
West China Hospital of Sichuan University
Chengdu, China
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, China
The First People's Hospital of Kashi Prefecture, Xinjiang
Kashgar, China
Incidence and severity of cell therapy-related adverse events (AEs) as assessed by CTCAE (V5.0)
Incidence and severity of cell therapy-related adverse events (AEs) from the first dosing to 28 days after the last dosing
Time frame: 28 days
Maximum tolerated dose (MTD)
Maximum tolerated dose (MTD) with multiple administrations.
Time frame: 28 days
Incidence and severity of treatment- emergent adverse events
Incidence and severity of cell treatment-emergent adverse events (AEs) as assessed by CTCAE v5.0 from the first dosing to 24 weeks after the last dosing.
Time frame: 24 weeks
DLCO changes from baseline
Changes from baseline in the percentage of diffusing capacity of the lung for carbon monoxide (DLCO) to the predicted value at 1 week, 4 weeks, 12 weeks, and 24 weeks after the last dosing.
Time frame: At baseline, 1, 4, 12 and 24 weeks
FVC changes from baseline
Changes from baseline in the forced vital capacity (FVC) at 1 week, 4 weeks, 12 weeks, and 24 weeks after the last dosing.
Time frame: At baseline, 1, 4, 12 and 24 weeks
Exercise capacity changes from baseline
Changes from baseline in the 6-minute walk test distance at 1 week, 4 weeks, 12 weeks, and 24 weeks after the last dosing.
Time frame: At baseline, 1, 4, 12 and 24 weeks
St. George's Respiratory Questionnaire
Changes from baseline in the St. George's Respiratory Questionnaire (SGRQ) total score at 1 week, 4 weeks, 12 weeks, and 24 weeks after the last dosing. The SGRQ is a 50-item questionnaire developed to measure health status (quality of life). Scores are calculated for three domains: Symptoms, Activity and Impacts. The total score (summed weights) can range from 0 to 100 with a lower score denoting a better health status.
Time frame: At baseline, 1, 4, 12 and 24 weeks
Symptoms of dyspnea
Changes from baseline in the dyspnea score at 1 week, 4 weeks, 12 weeks, and 24 weeks after the last dosing.
Time frame: At baseline, 1, 4, 12 and 24 weeks
Symptoms of cough
Changes from baseline in the cough score at 1 week, 4 weeks, 12 weeks, and 24 weeks after the last dosing.
Time frame: At baseline, 1, 4, 12 and 24 weeks
Tumor biomarkers
Changes from baseline in the lung tumor markers of CYFRA21-1, NSE, SCC, CEA and CA125 at 12 weeks and 24 weeks after the last dosing.
Time frame: At baseline, 12 and 24 weeks
Chest imaging changes
Changes from baseline in the chest HRCT score at 12 weeks and 24 weeks after the last dosing.
Time frame: At baseline, 12 and 24 weeks
Acute exacerbations of IPF
Frequency and severity of acute exacerbations of IPF from the first dosing to 24 weeks after the last dosing.
Time frame: 24 weeks
T lymphocyte subpopulations
Changes from baseline in the percentages of CD3+, CD4+, CD8+, CD4+/CD8+ in peripheral blood at 1 week, 4 weeks, and 12 weeks after the last dosing.
Time frame: At baseline, 1, 4 and 12 weeks
IgG and IgM levels
Changes from baseline in IgG levels in peripheral blood up to 12 weeks after the last dosing; Changes from baseline in IgM levels in peripheral blood up to 4 weeks after the last dosing.
Time frame: At baseline, 12 or 4 weeks
Inflammatory cytokines
Changes from baseline in the cytokines of TNF-α, IFN-γ, TGF-β, IL-1, IL-2, IL-4, IL-5, IL-6 and CCL2 in peripheral blood at 1 week, 4 weeks, and 12 weeks after the last dosing.
Time frame: At baseline, 1, 4 and 12 weeks
Serum complement levels
Changes from baseline in the serum complements of C3 and C4 in peripheral blood at 1 week, 4 weeks, and 12 weeks after the last dosing.
Time frame: At baseline, 1, 4 and 12 weeks
Blood proteomics analysis
Changes from baseline in the blood proteomic analysis at 1 week, 4 weeks, 12 weeks, and 24 weeks after the last dosing.
Time frame: At baseline, 1, 4, 12 and 24 weeks
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