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

ConditionsIgG4 Related Disease Systemic Sclerosis (SSc)

Trial statusNot yet recruiting

Trial phaseEarly Phase 1

Trial typeInterventional

Biological sexAll

Age18-80

SponsorQiubai Li

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

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).

Disqualifiers

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.

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.

Trial design

Design model

Sequential

Treatments tested in this trial

nebulized human umbilical cord mesenchymal stromal cell-derived extracellular vesicles
Biological/Vaccine
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.

Treatment groups

18 Participants

are divided into 1 treatment group

Group A: UC-EVs armExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame

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.

Time frame

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

Secondary outcomes

Change From Baseline in Health Assessment Questionnaire Score

Absolute change from baseline in Health Assessment Questionnaire (HAQ) score during the study. HAQ is a participant-reported outcome measure used to assess physical function and daily activity. The total score ranges from 0 to 3, with higher scores indicating worse physical function and greater difficulty in daily activities. A decrease from baseline indicates improvement.

Time frame

Baseline through Week 52

Change From Baseline in Patient Global Impression of Severity Score

Absolute change from baseline in Patient Global Impression of Severity (PGI-S) score during the study. PGI-S is used to assess the participant's overall perception of disease severity. The score ranges from 0 to 7, with higher scores indicating more severe disease symptoms. A decrease from baseline indicates improvement.

Time frame

Baseline through Week 52

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

Absolute change from baseline in St. George's Respiratory Questionnaire (SGRQ) score during the study. SGRQ is a participant-reported outcome measure used to assess respiratory symptoms, activity limitation, and disease impact. The total score ranges from 0 to 100, with higher scores indicating worse respiratory health status. A decrease from baseline indicates improvement.

Time frame

Baseline through Week 52

Change From Baseline in Leicester Cough Questionnaire Score

Absolute change from baseline in Leicester Cough Questionnaire (LCQ) score during the study. LCQ is a participant-reported outcome measure used to assess cough-related quality of life. The total score ranges from 3 to 21, with higher scores indicating better cough-related quality of life. An increase from baseline indicates improvement.

Time frame

Baseline through Week 52

Other outcomes

Change From Baseline in Bronchoalveolar Lavage Fluid Cellular and Cytokine Profiles

In participants who voluntarily undergo bronchoscopy and bronchoalveolar lavage fluid (BALF) collection, changes from baseline in BALF cellular characteristics and key inflammatory or immune-related cytokine levels will be assessed to explore local lung inflammation and immune microenvironment changes after UC-EV treatment.

Time frame

Baseline and Week 12

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Qiubai Li

Lead sponsor

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

Sponsor institution

Peking Union Medical College Hospital

Collaborator

Shandong Qilu Stem Cells Engineering Co., Ltd.

Collaborator

Source ClinicalTrials.gov

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