Nebulized UC-EVs for Recurrent or Refractory IMIDs With Lung Involvement

NCT07806045 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: UCEV-IMID 2.0
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Immune-mediated inflammatory diseases (IMIDs) are systemic inflammatory disorders driven by dysregulated immune responses that can affect multiple organs, including the lungs. Examples include Behçet disease, IgG4-related disease, and systemic sclerosis (SSc). IMID-related lung involvement may cause progressive lung damage, impaired lung function, disability, and increased mortality, but effective targeted treatment options remain limited. This clinical trial will study nebulized human umbilical cord mesenchymal stromal cell-derived extracellular vesicles, also called UC-EVs, in adults with recurrent or refractory IMIDs with lung involvement.

Conditions

IgG4 Related Disease; Systemic Sclerosis (SSc)

Keywords

IgG4 Related Disease; Systemic Sclerosis (SSc); Extracellular Vescicles; Umbilial Cord Mesenchymal Stromal Cell

Outcome Measures

Primary Outcomes (2)

• Incidence and Severity of Adverse Events and Serious Adverse Events

  The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) will be assessed in participants who receive at least one dose of nebulized UC-EVs. AEs and SAEs will be collected throughout the study and graded according to the protocol-defined safety assessment criteria.

  From first dose through Week 52

• Maximum Tolerated Dose and Recommended Phase 2 Dose of Nebulized UC-EVs

  The maximum tolerated dose (MTD), if determinable, and the recommended Phase 2 dose (RP2D) of nebulized UC-EVs will be determined based on dose-limiting toxicities (DLTs), overall safety and tolerability, and available clinical and laboratory safety data during the dose-escalation phase.

  Through the first 14-day treatment cycle for each dose cohort

Secondary Outcomes (14)

• Change From Baseline in Health Assessment Questionnaire Score

  Baseline through Week 52

• Change From Baseline in Patient Global Impression of Severity Score

  Baseline through Week 52

• Change From Baseline in St. George's Respiratory Questionnaire Score

  Baseline through Week 52

• Change From Baseline in Leicester Cough Questionnaire Score

  Baseline through Week 52

• Change From Baseline in Forced Vital Capacity at Week 24

  Baseline to Week 24

Other Outcomes (1)

• Change From Baseline in Bronchoalveolar Lavage Fluid Cellular and Cytokine Profiles

  Baseline and Week 12

Study Arms (1)

UC-EVs arm

EXPERIMENTAL

This open-label, dose-escalation study with up to three dose levels of nebulized UC-EVs. The maximum tolerated dose (MTD) of nebulized UC-EVs will be determined using dose-escalation 3+3 design. Dose Level 1: 5×10\^9 particles Dose Level 2: 1×10\^10 particles Dose Level 3: 2×10\^10 particles

Biological: nebulized human umbilical cord mesenchymal stromal cell-derived extracellular vesicles

Interventions

nebulized human umbilical cord mesenchymal stromal cell-derived extracellular vesicles BIOLOGICAL

UC-EVs are extracellular vesicles derived from human umbilical cord mesenchymal stromal cells. Participants will receive UC-EVs by nebulized inhalation once daily for 7 consecutive days, followed by 7 days without treatment. Each 14-day cycle will be repeated for 6 cycles over approximately 12 weeks.

Also known as: UC-EVs

UC-EVs arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 80 years, inclusive, regardless of sex.
• Good compliance and willingness to receive study treatment and complete follow-up visits and assessments as required by the protocol.
• For participants with IgG4-related disease:
• Diagnosis of IgG4-related disease for at least 6 months, according to the 2019 ACR/EULAR Classification Criteria or the 2020 Revised Comprehensive Diagnostic Criteria for IgG4-related Disease.
• Evidence of IgG4-related lung involvement, including but not limited to bronchial wall thickening, bronchovascular bundle thickening, pulmonary nodules, or interstitial lung disease on chest high-resolution computed tomography (HRCT).
• For participants with systemic sclerosis:
• Diagnosis of systemic sclerosis for at least 6 months, according to the 2013 ACR/EULAR Classification Criteria.
• Evidence of lung involvement on chest HRCT, including bronchial involvement, pulmonary nodules considered related to the underlying disease, and/or interstitial lung disease, with or without impaired pulmonary function.
• Able to understand the study purpose, procedures, and possible discomforts, and willing to provide written informed consent.
• Female participants of childbearing potential and male participants, including their female partners, must use highly effective contraception from screening until at least 6 months after the last dose. Participants must have no plan for pregnancy, sperm donation, or egg donation from screening until at least 6 months after the last dose.

You may not qualify if:

• Diagnosis before screening of any connective tissue disease other than IgG4-related disease or systemic sclerosis, or diagnosis of another interstitial lung disease, such as idiopathic pulmonary fibrosis or interstitial pneumonia with autoimmune features.
• Inadequate organ function reserve, including any of the following:
• Respiratory system: pulmonary arterial hypertension with pulmonary artery systolic pressure greater than 55 mmHg by echocardiography or mean pulmonary arterial pressure greater than 40 mmHg by right heart catheterization; severe impairment of diffusing capacity of the lung for carbon monoxide, defined as DLCO less than 30% of predicted; respiratory failure, defined as arterial oxygen tension less than 8 kPa or less than 60 mmHg and/or arterial carbon dioxide tension greater than 6.7 kPa or greater than 50 mmHg at rest without oxygen supplementation.
• Renal function: creatinine clearance less than 30 mL/min/1.73 m².
• Cardiac function: clinical symptoms of refractory congestive heart failure; left ventricular ejection fraction less than 35% by myocardial scintigraphy or echocardiography; chronic atrial fibrillation requiring oral anticoagulation; uncontrolled ventricular arrhythmia; or pericardial effusion causing hemodynamic instability by echocardiography.
• Liver function: persistent alanine aminotransferase, aspartate aminotransferase, or bilirubin greater than 3 times the upper limit of normal, or severe hepatic impairment, Child-Pugh class C.
• Allergic constitution or history of potentially life-threatening drug allergy.
• Clinically significant chronic or recurrent infection, defined as 3 or more infections of the same type within 1 year, or recent severe infection, such as pneumonia or sepsis. Participants will also be excluded if, within 1 month before baseline, they required inhaled, intramuscular, or systemic antibiotic treatment, systemic antiviral treatment, hospitalization, or prolonged hospitalization for infection.
• History of organ transplantation or currently awaiting organ transplantation.
• Positive screening test results for hepatitis B, hepatitis C, human immunodeficiency virus, or syphilis, as defined below:
• Hepatitis B surface antigen positive.
• Hepatitis B surface antigen negative but hepatitis B core antibody positive, with hepatitis B virus DNA above the upper limit of normal.
• Hepatitis C virus antibody positive, with hepatitis C virus RNA above the upper limit of normal.
• Human immunodeficiency virus antibody positive.
• Treponema pallidum antibody positive with positive rapid plasma reagin or toluidine red unheated serum test.

Sponsors & Collaborators

• Shandong Qilu Stem Cells Engineering Co., Ltd.: collaborator
• Qiubai Li: lead
• Peking Union Medical College Hospital: collaborator

Study Sites (1)

Peking Union Medical College Hospital

Beijing, China

Location

MeSH Terms

Conditions

Immunoglobulin G4-Related Disease; Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Autoimmune Diseases; Immune System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Qiubai Li, MD

  Department of Rheumatology, Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qiubai Li, MD

CONTACT

+86 13995671635; qiubaili@hust.edu.cn

Jingna Li, MD

CONTACT

+86 19801116153; lijingna0615@126.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 29, 2026
• First Posted: September 8, 2026
• Study Start (Estimated): October 14, 2026
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): July 30, 2029
• Last Updated: September 8, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)