Safety and Efficacy of Small Extracellular Vesicles Nebulizer in Patients With Allergic Rhinitis Complicated With Asthma

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Asthma; Allergic Rhinitis
• Intervention / Treatment: Other: hUC-MSC-sEV-002 Nebulizer; Other: hUC-MSC-sEV-002 Mimetic (Normal Saline)

Detailed Description

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.

Questionnaire (RQLQ) scores, Total Nasal Symptom Score (TNSS), Visual Analog Scale (VAS) scores, Asthma Control Test (ACT) scores, forced expiratory volume in one second (FEV₁), and peak expiratory flow (PEF) at Week 24 of treatment.

Secondary efficacy endpoints include the percentage changes from baseline in the Rhinitis Quality of Life Questionnaire (RQLQ) scores, Total Nasal Symptom Score (TNSS), and Visual Analog Scale (VAS) scores at the end of Week 2, end of Week 4, and Week 12 of treatment; the percentage changes from baseline in forced expiratory volume in one second (FEV₁), peak expiratory flow (PEF), and Asthma Control Test (ACT) scores at the end of Week 2, end of Week 4, and Week 12 of treatment; the percentage changes from baseline in total serum IgE, specific IgE, and IgG4 levels at Week 12 and Week 24 of treatment; and the changes in nasal endoscopy findings and nasal exhaled nitric oxide test results from baseline to Week 12 and Week 24 of treatment.

Exploratory endpoints include the changes from baseline in plasma cytokines (IFN-γ, IL-6, IL-4, IL-5, IL-13), peripheral blood lymphocytes, and the subsets of Th1, Th2, Th17 and ILC2 at the end of Week 2, Week 12 and Week 24 of treatment; as well as the changes from baseline in nasal secretion cytokines (ECP, IL-6, IFN-γ, IL-5, IL-13, IL-33) at the end of Week 2, Week 12 and Week 24 of treatment.

All adverse events occurring in all subjects during the clinical study shall be monitored closely. The adverse event forms shall be completed in a timely manner, with detailed documentation of clinical manifestations, severity, time of onset, duration, measures taken and clinical outcomes. The study shall not be initiated until the clinical study protocol and the informed consent form have been submitted to and approved by the Institutional Review Board (IRB).

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yan Jiang, MD; Phone Number: +86-532-82915920; Email: jiangyanoto@qdu.edu.cn
• Study Contact Backup: Name: Shengnan Zhang, MMed; Phone Number: +8618661808533; Email: zhangshengnan0102@163.com

Study Locations

• China
  • Chongqing, China, 401121
    • Chongqing General Hospital
    • Contact: Wei Yuan, MD; Phone Number: +8613368228269; Email: yuanwei@ucas.ac.cn
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-sen University
      • Contact: Qingling Fu, MD; Phone Number: +8613699726862; Email: fuqingl@mail.sysu.edu.cn
    • Guangzhou, Guangdong, China, 510630
      • The Third Affiliated Hospital of Sun Yat-Sen University
      • Contact: Qintai Yang, MD; Phone Number: +8613724859848; Email: yangqint@mail.sysu.edu.cn
  • Shandong
    • Qingdao, Shandong, China, 266100
      • The affiliated hospital of Qingdao university
      • Contact: Shengnan Zhang, MMed; Phone Number: +8618661808533; Email: zhangshengnan0102@163.com
    • Tai’an, Shandong, China, 271000
      • The Second Affiliated Hospital of Shandong First Medical University
      • Contact: Deli Wang, MMed; Phone Number: +8615621335297; Email: WDLWNY@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18-60 years, regardless of gender;
2. 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;
3. Suboptimal response to antiallergic medication treatment for one year prior to enrollment;
4. Patients who decline allergen-specific immunotherapy, or have no available specific therapy for the relevant allergen, or failed allergen-specific immunotherapy;
5. Females of childbearing potential must agree to avoid pregnancy during study participation and for 30 days after the final visit;
6. 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.

Exclusion Criteria:

1. Complicated with other nasal and sinus diseases that may affect the reasonable assessment of efficacy and/or safety;
2. Suffering from uncontrolled asthma or poorly controlled asthma symptoms;
3. Suffering from malignant tumors, severe immune diseases, long-term use of immunosuppressants, or immunodeficiency;
4. Having unstable conditions due to respiratory tract infection and/or acute asthma exacerbation within 4 weeks prior to the initial screening visit;
5. Currently receiving treatment with beta-blockers or angiotensin-converting enzyme (ACE) inhibitors;
6. Suffering from mental illnesses;
7. Suffering from severe systemic diseases, such as cases of peptic ulcers, diabetes mellitus, and heart failure;
8. Specific infections such as syphilis, leprosy, and tuberculosis;
9. Females who are currently pregnant, planning to become pregnant soon, or breastfeeding;
10. 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;
11. Patients who are currently receiving allergen desensitization therapy or biologic therapy;
12. Positive for hepatitis B surface antigen, hepatitis C virus antibody, syphilis serological antibody, or human immunodeficiency virus (HIV) antibody;
13. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Other: hUC-MSC-sEV-002 Nebulizer; Nebulization therapy, once daily, 5 nebulizations per week, for 2 consecutive weeks, totaling 10 times.
Placebo Comparator: 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.	Other: hUC-MSC-sEV-002 Mimetic (Normal Saline); Nebulization therapy, once daily, 5 nebulizations per week, for 2 consecutive weeks, totaling 10 times.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)	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.	At Week 24
Forced Expiratory Volume in One Second (FEV1)	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.	At Week 24
Drug-related adverse reaction rate	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.	In the short term after treatment (0-24 hours)；At Week 2
Blood Pressure	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.	At Week 2
Changes in routine blood test	We performed routine blood tests via venous blood collection and recorded any changes compared with baseline.	At Week 2
Changes in routine urine test	Urine specimens were collected for routine urinalysis, and any abnormal changes from baseline were documented.	At Week 2
Whether abnormal changes occurred in the ECG	Electrocardiography (ECG) will be performed to evaluate whether there are any abnormalities in the patient's heart rate or cardiac rhythm.	At Week 2
Total Nasal Symptom Score (TNSS)	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.	At Week 24
Visual Analog Scale (VAS)	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.	At Week 24
Asthma Control Test (ACT)	It is used to assess asthma control, with the total score ranging from 0 to 25. A higher total score indicates better asthma control.	At Week 24
Peak Expiratory Flow (PEF)	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.	At Week 24
Heart Rate	The unit of heart rate is beats per minute, with a normal range of 60 to 100 bpm.	At Week 2
Body Temperature	The unit is degrees Celsius (°C), with a normal range of 36.0 °C to 37.0 °C.	At Week 2
C-reactive protein (CRP)	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.	At Week 2
Alanine aminotransferase (ALT)	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.	At Week 2
Creatinine	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.	At Week 2
IgG, IgA, IgM, C3 ,C4	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.	At Week 2
Aspartate aminotransferase (AST)	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.	At Week 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse event rate	The incidence of adverse events at 12 and 24 weeks post-treatment.	At Week 12; At Week 24
Blood Pressure	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.	At Week 12; At Week 24
Changes in routine blood test	We performed routine blood tests via venous blood collection and recorded any changes compared with baseline.	At Week 12; At Week 24
Changes in routine urine test	Urine specimens were collected for routine urinalysis, and any abnormal changes from baseline were documented.	At Week 12; At Week 24
Whether abnormal changes occurred in the ECG	Electrocardiography (ECG) will be performed to evaluate whether there are any abnormalities in the patient's heart rate or cardiac rhythm.	At Week 12; At Week 24
Chest X-ray	A chest X-ray shall be performed at Week 24 of treatment to evaluate for any abnormal pulmonary imaging findings.	At Week 24
Rhinitis-Conjunctivitis Quality of Life Questionnaire（RQLQ）	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.	At Week 2; At Week 4; At Week 12
Forced Expiratory Volume in 1 second（FEV1）	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.	At Week 2; At Week 4; At Week 12; At Week 24
Total Serum Immunoglobulin E (IgE)	Venous blood samples are collected for total serum IgE testing, with the unit of IU/mL. The normal range is 0 to 100 IU/mL.	At Week 12; At Week 24
Nasal endoscopy	Nasal endoscopy shall be performed to assess for any structural abnormalities or abnormal hyperplastic lesions in the nasal cavity, and to evaluate for any abnormal changes in the nasal mucosa.	After 12 weeks of treatment；After 24 weeks of treatment
Nasal Exhaled Nitric Oxide	The concentration of nitric oxide in nasal exhalation is measured using a nasal exhaled nitric oxide analyzer.	At Week 12; At Week 24
Heart Rate	The unit of heart rate is beats per minute, with a normal range of 60 to 100 bpm.	At Week 12; At Week 24
Body Temperature	The unit is degrees Celsius (°C), with a normal range of 36.0 °C to 37.0 °C.	At Week 12; At Week 24
C-reactive protein (CRP)	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.	At Week 12; At Week 24
Alanine aminotransferase (ALT)	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.	At Week 12; At Week 24
Creatinine	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.	At Week 12; At Week 24
IgG, IgA, IgM, C3,C4	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.	At Week 12; At Week 24
Peak Expiratory Flow (PEF)	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.	At Week 2; At Week 4;At Week 12; At Week 24
Total Nasal Symptom Score (TNSS)	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.	At Week 2; At Week 4; At Week 12
Visual Analog Scale (VAS)	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.	At Week 2; At Week 4; At Week 12
Asthma Control Test (ACT)	It is used to assess asthma control, with the total score ranging from 0 to 25. A higher total score indicates better asthma control.	At Week 2; At Week 4; At Week 12
Specific Immunoglobulin E (sIgE)	Venous blood samples are collected for specific IgE (sIgE) testing, with the unit of kU/L. The normal value is less than 60 kU/L.	At Week 12; At Week 24
Immunoglobulin G4 (IgG4)	Venous blood samples are collected for IgG4 testing, with the unit of g/L. The normal range is 0.03 to 2.01 g/L.	At Week 12; At Week 24
Aspartate aminotransferase (AST)	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.	At Week 12; At Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Cytokines	Venous blood samples are collected for the measurement of plasma cytokines, including IFN-γ, IL-6, IL-4, IL-5 and IL-13. The units for these indicators are all pg/ml.This indicator is an exploratory measure, and no normal reference range is available.	At Week 2; At Week 12; At Week 24
Nasal secretion cytokines	Nasal secretion cytokines include ECP, IL-6, IFN-γ, IL-5, IL-13, and IL-33.The units for these indicators are all pg/ml. These are exploratory measures, and no normal reference range is available.	At Week 2; At Week 12; At Week 24
Peripheral Blood Lymphocyte Subsets	Peripheral blood lymphocyte subset analysis includes Th1, Th2, Th17, and ILC2. This is an exploratory endpoint, and no normal reference range is available.	At Week 2; At Week 12; At Week 24

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Qingdao University
• Investigators: Principal Investigator: Yan Jiang, MD, The affiliated hospital of Qingdao university

Study record dates

Study Major Dates

• Study Start (Estimated): March 5, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: December 23, 2025
• First Submitted That Met QC Criteria: February 27, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Asthma; Allergic rhinitis; Small extracellular vesicles; Nebulizer formulation; Randomized, double-blind
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Nose Diseases; Otorhinolaryngologic Diseases; Rhinitis; Asthma; Rhinitis, Allergic; Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Solutions; Saline Solution
• Other Study ID Numbers: QYFYEC2025-192

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The informed consent form of this study does not include clauses authorizing IPD sharing. As a Phase I/II exploratory study, the data involves sensitive medical information and preliminary research results. To protect participants' privacy and comply with ethical and regulatory requirements, the data will not be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No