Safety and Preliminary Efficacy of Small Extracellular Vesicles (Code: hUC-MSC-sEV-002) Nebulizer in Patients With Allergic Rhinitis Complicated With Asthma: A Multicenter, Prospective, Randomized, Double-Blind Phase I/II Clinical Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 18
- 试验地点
- 5
- 主要终点
- Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
研究概览
简要总结
This trial aims to evaluate the safety, tolerability and efficacy of hUC-MSC-sEV-002 nebulizer in patients with allergic rhinitis and asthma. It consists of two parts: ① Single-center dose exploration (The Affiliated Hospital of Qingdao University): A 3+3 escalation design will test three doses (1×10⁸, 1×10⁹, 1×10¹⁰ particles/mL) to determine the maximum tolerated dose (MTD).Three subjects will be enrolled in each dose group. If no Dose-Limiting Toxicity (DLT) is observed among the 3 subjects, the study may proceed to the next dose exploration. If 1 out of the 3 subjects experiences DLT, an additional 3 subjects will be enrolled in the same dose group; the study may move to the next dose exploration only if no DLT is observed in these additional 3 subjects. If more than 1 out of the 3 subjects develops DLT, the previous dose group will be defined as the MTD. A total of at least 9 and at most 18 subjects will be recruited for this clinical trial. ② Multi-center case expansion: Participants will be randomized 2:1 to hUC-MSC-sEV-002 or placebo groups for efficacy comparison.Eligibility criteria: 18-60 years old; moderate-to-severe allergic rhinitis (ARIA guidelines) with positive inhaled allergen skin test; asthma diagnosed per GINA 2022; signed informed consent.Intervention: Nebulization once daily (5 times/week, 2 weeks, 10 doses total). Follow-up visits at baseline, Week 2, 4, 12, 24, including symptom scales, lung function tests, nasal endoscopy, nasal exhaled nitric oxide test, chest X-ray, blood tests, and electrocardiogram. The trial is approved by the Medical Ethics Committee of The Affiliated Hospital of Qingdao University (No. QYFYEC2025-192). Participants may withdraw anytime without affecting medical care. Study period: Aug 2025-Aug 2027. Sample size: 9-18 for Part 1; Part 2 size based on Part 1 results.
详细描述
Allergic rhinitis is an independent risk factor for asthma. As inflammatory disorders affecting the upper and lower airways respectively, allergic rhinitis and asthma share similar pathogenesis and interact with each other, thus being recognized as "one airway, one disease". Their incidence rates are increasing year by year with a wide distribution, and they often coexist. These conditions have become an important issue affecting people's quality of life worldwide and imposed a heavy economic burden on society. In the treatment of allergic rhinitis complicated with asthma, glucocorticoids, antihistamines, leukotriene receptor antagonists and other agents are the most commonly used drugs. However, long-term use of these drugs is prone to induce various adverse reactions. Moreover, drug resistance and intolerance observed in some patients have also limited the widespread application of these medications. Therefore, there is an urgent need for novel therapeutic approaches for allergic diseases.
Small extracellular vesicles derived from mesenchymal stem cells not only possess immunomodulatory functions similar to those of mesenchymal stem cells, but also exhibit more advantages in clinical applications, including no tumorigenic risk, small size, stable performance, easy transportation and preservation, low immunogenicity, and the ability to penetrate biological barriers. Therefore, they hold great potential and broad application prospects in the treatment of allergic rhinitis complicated with asthma.
This is a multicenter, prospective, randomized, double-blind, placebo-controlled, dose-finding clinical trial, designed to evaluate the safety and preliminary efficacy of nebulized human umbilical cord blood mesenchymal stem cell-derived small extracellular vesicles (code: hUC-MSC-sEV-002) in the treatment of allergic rhinitis complicated with asthma. The trial consists of two phases, namely the dose-finding phase (Phase I clinical trial) and the cohort expansion phase (Phase II clinical trial). It encompasses three study periods: the screening period (Visit 0, Weeks -2 to 0), the treatment period (Visit 1, Week 2), and the follow-up period (Visit 2, Week 4; Visit 3, Week 12; Visit 4, Week 24). The scheduled visit plan includes baseline assessment, the end of Week 2, the end of Week 4, Week 12, and Week 24.
Primary safety endpoints include dose-limiting toxicities (DLT) associated with nebulized hUC-MSC-sEV-002, covering the following aspects: the incidence of drug-related adverse reactions occurring within the short-term post-treatment period (0 to 24 hours); the incidence of drug-related adverse reactions within 2 weeks of treatment; changes in vital signs, complete blood count plus C-reactive protein (CRP), urine routine, liver and kidney function, immune profile panel (IgG, IgA, IgM, C3, C4), and electrocardiogram (ECG) from baseline to the end of Week 2 of treatment.
Secondary safety endpoints include the incidence of adverse events at Week 12 and Week 24 of treatment; changes in vital signs, complete blood count, urine routine, liver and kidney function, immune profile panel, and electrocardiogram (ECG) from baseline to Week 12 and Week 24 of treatment; pulmonary function tests at Week 2 and Week 24 of treatment; and chest X-ray examination at Week 24 of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18-60 years, regardless of gender;
- •Patients with moderate to severe allergic rhinitis (with sleep/work/study/daily activity impairment or distressing symptoms) meeting the diagnostic criteria of the international Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, positive for at least one inhalant allergen skin prick test, and concurrent asthma complying with the Global Initiative for Asthma (GINA) 2022 guidelines;
- •Suboptimal response to antiallergic medication treatment for one year prior to enrollment;
- •Patients who decline allergen-specific immunotherapy, or have no available specific therapy for the relevant allergen, or failed allergen-specific immunotherapy;
- •Females of childbearing potential must agree to avoid pregnancy during study participation and for 30 days after the final visit;
- •Subjects or their legal representatives must be able to sign the informed consent form and comply with the study requirements for medication administration and follow-up.
排除标准
- •Complicated with other nasal and sinus diseases that may affect the reasonable assessment of efficacy and/or safety;
- •Suffering from uncontrolled asthma or poorly controlled asthma symptoms;
- •Suffering from malignant tumors, severe immune diseases, long-term use of immunosuppressants, or immunodeficiency;
- •Having unstable conditions due to respiratory tract infection and/or acute asthma exacerbation within 4 weeks prior to the initial screening visit;
- •Currently receiving treatment with beta-blockers or angiotensin-converting enzyme (ACE) inhibitors;
- •Suffering from mental illnesses;
- •Suffering from severe systemic diseases, such as cases of peptic ulcers, diabetes mellitus, and heart failure;
- •Specific infections such as syphilis, leprosy, and tuberculosis;
- •Females who are currently pregnant, planning to become pregnant soon, or breastfeeding;
- •Patients who are currently participating in other clinical trials or have participated in other clinical trials within 30 days prior to the initial screening visit;
- •Patients who are currently receiving allergen desensitization therapy or biologic therapy;
- •Positive for hepatitis B surface antigen, hepatitis C virus antibody, syphilis serological antibody, or human immunodeficiency virus (HIV) antibody;
- •In addition to the above conditions, patients will be excluded if the investigators consider them unsuitable for participation in this clinical study for other reasons.
研究组 & 干预措施
hUC-MSC-sEV-002 nebulizer
hUC-MSC-sEV-002 nebulizer, nebulization therapy, once daily, 5 nebulizations per week, for 2 consecutive weeks, totaling 10 times.
干预措施: hUC-MSC-sEV-002 Nebulizer (Other)
hUC-MSC-sEV-002 Mimetic (Normal Saline)
A control arm is established in Phase II of the clinical trial.hUC-MSC-sEV-002 Mimetic (Normal Saline), nebulization therapy, once daily, 5 nebulizations per week, for 2 consecutive weeks, totaling 10 times.
干预措施: hUC-MSC-sEV-002 Mimetic (Normal Saline) (Other)
结局指标
主要结局
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
时间窗: At Week 24
It consists of 7 domains and 28 items, with each item scored on a scale of 0 to 6. Each domain is scored independently, and the sum of all domain scores yields the total RQLQ score, which ranges from 0 to 168. A higher total score indicates a greater negative impact of the disease on the patient's quality of life.
Forced Expiratory Volume in One Second (FEV1)
时间窗: At Week 24
Pulmonary function tests are conducted to obtain the value of FEV1, with the unit of FEV1 being liters (L). A percentage of the measured FEV1 value relative to the predicted value of 80% or higher is defined as normal.
Drug-related adverse reaction rate
时间窗: In the short term after treatment (0-24 hours)；At Week 2
The incidence of treatment-related adverse events within the short-term post-treatment period (0 to 24 hours);The incidence of treatment-related adverse events at 2 weeks post-treatment.
Blood Pressure
时间窗: At Week 2
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) shall be measured separately. The reference range for SBP is 90 mmHg to 139 mmHg, and the reference range for DBP is 60 mmHg to 89 mmHg.
Changes in routine blood test
时间窗: At Week 2
We performed routine blood tests via venous blood collection and recorded any changes compared with baseline.
Changes in routine urine test
时间窗: At Week 2
Urine specimens were collected for routine urinalysis, and any abnormal changes from baseline were documented.
Whether abnormal changes occurred in the ECG
时间窗: At Week 2
Electrocardiography (ECG) will be performed to evaluate whether there are any abnormalities in the patient's heart rate or cardiac rhythm.
Total Nasal Symptom Score (TNSS)
时间窗: At Week 24
It consists of 4 items, with each item scored on a scale of 0 to 3. The total score ranges from 0 to 12, with a higher total score indicating more severe disease symptoms.
Visual Analog Scale (VAS)
时间窗: At Week 24
It is used to assess the severity of symptoms, with the total score ranging from 0 to 10. A higher total score indicates more severe disease symptoms.
Asthma Control Test (ACT)
时间窗: At Week 24
It is used to assess asthma control, with the total score ranging from 0 to 25. A higher total score indicates better asthma control.
Peak Expiratory Flow (PEF)
时间窗: At Week 24
Pulmonary function tests are conducted to obtain the value of PEF, with the unit of PEF being liters per second (L/s). A percentage of the measured PEF value relative to the predicted value of 80% or higher is defined as normal.
Heart Rate
时间窗: At Week 2
The unit of heart rate is beats per minute, with a normal range of 60 to 100 bpm.
Body Temperature
时间窗: At Week 2
The unit is degrees Celsius (°C), with a normal range of 36.0 °C to 37.0 °C.
C-reactive protein (CRP)
时间窗: At Week 2
Venous blood sampling is performed for C-reactive protein (CRP) testing.The unit is mg/L, with a normal reference range of 0 to 5 mg/L.
Alanine aminotransferase (ALT)
时间窗: At Week 2
Venous blood sampling is performed for liver function tests. Alanine aminotransferase (ALT) is measured in U/L, with a normal reference range of 7-40 U/L for females and 9-50 U/L for males.
Creatinine
时间窗: At Week 2
Venous blood sampling is performed for renal function tests.The unit for creatinine is μmol/L, with a normal reference range of 41-81 μmol/L for females and 57-111 μmol/L for males.
IgG, IgA, IgM, C3 ,C4
时间窗: At Week 2
Venous blood sampling is performed for five immunological indicators, which mainly includes IgG, IgA, IgM, C3 and C4.The units for all the above indicators are g/L. Normal reference ranges:IgG: 8.6-17.4 g/L；IgA: 1.0-4.2 g/L；IgM: 0.3-2.2 g/L；C3: 0.7-1.4 g/L；C4: 0.1-0.4 g/L.
Aspartate aminotransferase (AST)
时间窗: At Week 2
Venous blood sampling is performed for liver function tests. Aspartate aminotransferase (AST) is measured in U/L, with a normal reference range of 13-35 U/L for females and 15-40 U/L for males.
次要结局
- Adverse event rate(At Week 12; At Week 24)
- Blood Pressure(At Week 12; At Week 24)
- Changes in routine blood test(At Week 12; At Week 24)
- Changes in routine urine test(At Week 12; At Week 24)
- Whether abnormal changes occurred in the ECG(At Week 12; At Week 24)
- Chest X-ray(At Week 24)
- Rhinitis-Conjunctivitis Quality of Life Questionnaire（RQLQ）(At Week 2; At Week 4; At Week 12)
- Forced Expiratory Volume in 1 second（FEV1）(At Week 2; At Week 4; At Week 12; At Week 24)
- Total Serum Immunoglobulin E (IgE)(At Week 12; At Week 24)
- Nasal endoscopy(After 12 weeks of treatment；After 24 weeks of treatment)
- Nasal Exhaled Nitric Oxide(At Week 12; At Week 24)
- Heart Rate(At Week 12; At Week 24)
- Body Temperature(At Week 12; At Week 24)
- C-reactive protein (CRP)(At Week 12; At Week 24)
- Alanine aminotransferase (ALT)(At Week 12; At Week 24)
- Creatinine(At Week 12; At Week 24)
- IgG, IgA, IgM, C3,C4(At Week 12; At Week 24)
- Peak Expiratory Flow (PEF)(At Week 2; At Week 4;At Week 12; At Week 24)
- Total Nasal Symptom Score (TNSS)(At Week 2; At Week 4; At Week 12)
- Visual Analog Scale (VAS)(At Week 2; At Week 4; At Week 12)
- Asthma Control Test (ACT)(At Week 2; At Week 4; At Week 12)
- Specific Immunoglobulin E (sIgE)(At Week 12; At Week 24)
- Immunoglobulin G4 (IgG4)(At Week 12; At Week 24)
- Aspartate aminotransferase (AST)(At Week 12; At Week 24)
研究者
jiangyan
Chief Physician
The Affiliated Hospital of Qingdao University