Clinical trial NCT06919380: Nebulized MSC-Exos for Anti-MDA5+ RP-ILD: Safety and Efficacy Trial
Official title: Safety and Efficacy Study of Nebulized Mesenchymal Stem Cell-Derived Exosomes (MSC-exos) for the Treatment of Anti-MDA5 Positive Dermatomyositis-Associated Rapidly Progressive Interstitial Lung Disease (RP-ILD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Anti-MDA5 Positive Dermatomyositis-Associated RP-ILD
Rapidly Progressive Interstitial Lung Disease
Keywords: Interstitial Lung Disease
Anti-MDA5 Positive
Rapidly Progressive Interstitial Lung Disease
Lead sponsor: Guangzhou Medical University
Sponsor class: OTHER
First posted: 2025-04-09
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Objective: To assess the safety, tolerability, and efficacy of nebulized MSC-exos-P1 in patients with anti-MDA5 positive dermatomyositis-associated rapidly progressive interstitial lung disease (RP-ILD).

Design: Prospective interventional trial with 10 eligible patients aged 18-75, meeting criteria for RP-ILD and anti-MDA5 positivity. Primary endpoint is safety and tolerability, measured by adverse events within 30 days post-treatment. Secondary endpoints are clinical improvements on days 14 and 28, including serological indicators and chest HRCT scores.

Exclusions: Pregnant/breastfeeding individuals, severe allergies, active pulmonary infections, pulmonary embolism, extracorporeal support treatments, and other specified conditions.

Treatment: Nebulized MSC-exos-P1 daily for 14 days, plus standard care of corticosteroids and immunosuppressants.

Monitoring: Regular vital signs, oxygenation index, and pulmonary function tests. Follow-ups at multiple points up to 12 months.

Detailed description: This single-center, prospective interventional trial aims to evaluate the safety profile and potential efficacy of nebulized mesenchymal stem cell-derived exosomes (MSC-exos-P1) in anti-MDA5 positive dermatomyositis patients with rapidly progressive interstitial lung disease. Anti-MDA5 positive RP-ILD represents a critical clinical challenge with mortality rates exceeding 50% despite aggressive immunosuppressive therapy, highlighting the urgent need for novel treatment approaches.

The trial will enroll 10 eligible patients who will receive a 14-day course of daily nebulized MSC-exos-P1 while continuing standard immunosuppressive therapy. Safety monitoring will include daily vital signs, laboratory tests, and adverse event documentation during the treatment period. Efficacy assessments will measure changes in oxygenation parameters, pulmonary function, inflammatory biomarkers, and CT imaging findings at days 14 and 28 compared to baseline.

The scientific rationale for this intervention is based on preclinical evidence demonstrating the immunomodulatory, anti-inflammatory, and anti-fibrotic properties of MSC-derived exosomes. These nanoparticles have shown the ability to modify alveolar macrophage phenotypes, reduce pro-inflammatory cytokine production, and suppress fibroblast activation - mechanisms that may directly target the pathophysiological processes driving RP-ILD in this patient population. The nebulized delivery system enables direct targeting of affected lung tissue while minimizing systemic exposure.

Eligibility criteria: Inclusion Criteria:

* Patients are eligible for inclusion if they meet all of the following criteria:

  1. Positive for anti-MDA5 antibody dermatomyositis (according to the "Chinese Expert Consensus on the Diagnosis and Treatment of Anti-MDA5 Positive Dermatomyositis (2023 Edition)");
  2. Pulmonary lesions meet the diagnostic criteria for RP-ILD.

     Exclusion Criteria:
* Patients who meet any of the following criteria will be excluded from this study:

  1. Pregnant or breastfeeding women, or women planning pregnancy during the study, or men unwilling to use contraceptive measures throughout the trial period;
  2. History of severe allergies or allergies to the main active ingredients of the trial medication;
  3. Currently suffering from severe pulmonary infections, pneumothorax, or large pleural effusions;
  4. Currently diagnosed with pulmonary embolism;
  5. Currently undergoing mechanical ventilation through tracheal intubation;
  6. Currently undergoing extracorporeal life support treatments such as ECMO, CRRT, PMX-DHP, or plasma exchange;
  7. Currently suffering from severe heart failure, liver, or kidney insufficiency;
  8. Expected to undergo lung transplantation in the near future;
  9. Currently suffering from lung cancer or pulmonary nodules suspected to be early-stage lung cancer;
  10. Suffering from primary immunodeficiency diseases;
  11. Currently suffering from active infectious diseases, including but not limited to HIV positivity, active tuberculosis, etc., and deemed unsuitable for this trial by the researcher;
  12. Use of other trial medications within 28 days before starting treatment, which the researcher judges may interfere with the safety and efficacy assessment of this trial medication;
  13. Other situations deemed not in the best interest of the subject or unsuitable for participation in this study by the researcher, such as poor compliance.

Primary outcomes:
measure: Three-Month Mortality Rate and Safety of Nebulized MSC-exos P1
timeFrame: 3 months post-treatment initiation]
Secondary outcomes:
measure: Oxygen Saturation
timeFrame: Baseline, day 14, and day 28 post-treatment initiation
measure: CT Lesion Changes
timeFrame: Baseline, day 14, and day 28 post-treatment initiation
measure: Symptom Improvement
timeFrame: Baseline, day 14, and day 28 post-treatment initiation
measure: C-reactive Protein (CRP)
timeFrame: Baseline, day 14, and day 28 post-treatment initiation
measure: Interleukin-6 (IL-6)
timeFrame: Baseline, day 14, and day 28 post-treatment initiation
measure: D-dimer
timeFrame: Baseline, day 14, and day 28 post-treatment initiation
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
References: