A Phase I Open Label, Dose Escalation Study to Characterize the Safety, Tolerability, and Efficacy of VUM02 Injection in Subjects With Idiopathic Pulmonary Fibrosis
Overview
- Phase
- Phase 1
- Intervention
- VUM02 Injection
- Conditions
- Idiopathic Pulmonary Fibrosis
- Sponsor
- Wuhan Optics Valley Vcanbiopharma Co., Ltd.
- Enrollment
- 9
- Locations
- 4
- Primary Endpoint
- Maximum tolerated dose (MTD)
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must meet all of the following criteria to be eligible for this trial:
- •Gender unrestricted, aged between 40 and 75 years old (inclusive);
- •Diagnosed with IPF according to the 2022 Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.
- •In the 3 months prior to administration, determined by the investigator to have stable disease, with diffusing capacity of the lung for carbon monoxide (DLCO) between 30% and 79% of the predicted value (adjusted for Hb), FVC/predicted ≥50%, and forced expiratory volume in one second (FEV1)/FVC ≥0.70;
- •Allowed to enroll are the patients who have been treated according to the current standard treatment plan for IPF and have maintained the treatment for at least 3 months;
- •Good compliance, able to understand and cooperate with pulmonary function test procedures, willing to participate voluntarily in the trial according to the protocol requirements, and understand and sign the informed consent form voluntarily.
Exclusion Criteria
- •Patients meeting any of the following criteria are not eligible for this trial:
- •Allergic to any ingredient of the product;
- •Suffering from interstitial lung diseases (ILD) other than IPF, including but not limited to: any other type of interstitial pneumonia; lung diseases related to exposure to fibrogenic agents or other environmental toxins or drugs (such as amiodarone, bleomycin, or methotrexate); other types of occupational lung diseases; granulomatous lung diseases; systemic diseases including vasculitis, infectious diseases (i.e., tuberculosis), and connective tissue diseases, or a history of prior pulmonary resection;
- •During the screening period, having any of the following pulmonary diseases: asthma, pulmonary embolism, pneumothorax; lung cancer, obstructive bronchitis, or other active lung diseases; a known history of immune system diseases (such as thymic diseases, systemic lupus erythematosus); acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
- •Chest HRCT during the screening period shows emphysema area \> fibrosis area;
- •Previously received stem cell therapy or intolerant to cell therapy;
- •Received unstable standard of care for IPF within the 3 months prior to screening;
- •Used non-biological drugs with cell proliferation inhibition or immunosuppressive/immunomodulatory effects during the 3 months prior to screening, such as Mycophenolate Mofetil, cyclophosphamide, tacrolimus, and JAK inhibitors, as well as other Chinese herbal medicines with immunomodulatory effects;
- •Used biologics such as rituximab, TNF-α monoclonal antibodies, and IFN-γ monoclonal antibodies within the 6 months prior to screening;
- •Used anticoagulant drugs, sildenafil, bosentan, macitentan, imatinib, and other drugs for treating IPF within the 4 weeks prior to screening;
Arms & Interventions
VUM02 Injection (hUCT-MSCs)+Conventional treatment
3 predefined dose groups: 5x10\^7 cells/person/time, 1x10\^8 cells/person/time and 2x10\^8 cells/person/time, administered intravenously on D0, D3 and D6 for a total of 3 doses.
Intervention: VUM02 Injection
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD)
Time Frame: 28 days
Maximum tolerated dose (MTD) with multiple administrations.
Incidence and severity of cell therapy-related adverse events (AEs) as assessed by CTCAE (V5.0)
Time Frame: 28 days
Incidence and severity of cell therapy-related adverse events (AEs) from the first dosing to 28 days after the last dosing
Secondary Outcomes
- St. George's Respiratory Questionnaire(At baseline, 1, 4, 12 and 24 weeks)
- Symptoms of dyspnea(At baseline, 1, 4, 12 and 24 weeks)
- DLCO changes from baseline(At baseline, 1, 4, 12 and 24 weeks)
- Chest imaging changes(At baseline, 12 and 24 weeks)
- T lymphocyte subpopulations(At baseline, 1, 4 and 12 weeks)
- Incidence and severity of treatment- emergent adverse events(24 weeks)
- Exercise capacity changes from baseline(At baseline, 1, 4, 12 and 24 weeks)
- Serum complement levels(At baseline, 1, 4 and 12 weeks)
- Tumor biomarkers(At baseline, 12 and 24 weeks)
- Acute exacerbations of IPF(24 weeks)
- IgG and IgM levels(At baseline, 12 or 4 weeks)
- Inflammatory cytokines(At baseline, 1, 4 and 12 weeks)
- FVC changes from baseline(At baseline, 1, 4, 12 and 24 weeks)
- Symptoms of cough(At baseline, 1, 4, 12 and 24 weeks)
- Blood proteomics analysis(At baseline, 1, 4, 12 and 24 weeks)