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

NCT07453771 | Not Yet Recruiting

• 1 other identifier: QYFYEC2025-192
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Allergic Rhinitis; Asthma

Keywords

Small extracellular vesicles; Nebulizer formulation; Allergic rhinitis; Asthma; Randomized, double-blind

Outcome Measures

Primary Outcomes (18)

• 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 Outcomes (24)

• 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

Other Outcomes (3)

• Plasma Cytokines

  At Week 2; At Week 12; At Week 24

• Nasal secretion cytokines

  At Week 2; At Week 12; At Week 24

• Peripheral Blood Lymphocyte Subsets

  At Week 2; At Week 12; At Week 24

Study Arms (2)

hUC-MSC-sEV-002 nebulizer

EXPERIMENTAL

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

hUC-MSC-sEV-002 Mimetic (Normal Saline)

PLACEBO COMPARATOR

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)

Interventions

hUC-MSC-sEV-002 Nebulizer OTHER

Nebulization therapy, once daily, 5 nebulizations per week, for 2 consecutive weeks, totaling 10 times.

hUC-MSC-sEV-002 nebulizer

hUC-MSC-sEV-002 Mimetic (Normal Saline) OTHER

Nebulization therapy, once daily, 5 nebulizations per week, for 2 consecutive weeks, totaling 10 times.

hUC-MSC-sEV-002 Mimetic (Normal Saline)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Affiliated Hospital of Qingdao University: lead

Study Sites (5)

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

Location

The Third Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510630, China

Location

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, 266100, China

Location

The Second Affiliated Hospital of Shandong First Medical University

Tai’an, Shandong, 271000, China

Location

Chongqing General Hospital

Chongqing, 401121, China

Location

MeSH Terms

Conditions

Rhinitis, Allergic; Asthma

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Rhinitis; Nose Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Otorhinolaryngologic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Yan Jiang, MD

  The Affiliated Hospital of Qingdao University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yan Jiang, MD

CONTACT

+86-532-82915920; jiangyanoto@qdu.edu.cn

Shengnan Zhang, MMed

CONTACT

+8618661808533; zhangshengnan0102@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Model Details: This is a combined Phase 1/Phase 2 randomized, double-blind, placebo-controlled trial with distinct designs for each phase. Phase 1 is a dose-escalation stage to determine the safe dose range of hUC-MSC-sEV-002 nebulizer, without a control group; only subjects receive different doses of the investigational drug. Phase 2 is an expansion stage: eligible patients with allergic rhinitis and asthma are randomly assigned to the experimental (hUC-MSC-sEV-002 nebulizer) or control (matched placebo) group at 2:1 via block randomization. Both groups have identical administration route, frequency and treatment course. Double-blinding is maintained throughout the study for participants, investigators and outcome assessors until data locking and unblinding.

Study Record Dates

• First Submitted: December 23, 2025
• First Posted: March 6, 2026
• Study Start: March 5, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: March 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)