Safety and Efficacy of Allogeneic Mesenchymal Stem Cells in Patients With Rapidly Progressive Interstitial Lung Disease

Study Overview
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Brief Summary
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The study evaluates the safety and the efficacy of the addition of intravenous transplantation of donor bone marrow mesenchymal stem cells in patients with idiopathic interstitial pneumonia or connective tissue disease associated with interstitial lung disease, which have actively progressing disease with rapid loss of pulmonary function on the background of routine treatment.

Detailed Description
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Despite significant progress in the treatment of interstitial lung disease, achieved thanks to new drugs, such as pirfenidone and nintedanib, there are many patients for whom these drugs are not available or poorly tolerated. In addition significant evidence of their effectiveness and safety is valid only for idiopathic pulmonary fibrosis. The transplantation of allogeneic stem cells is a promising direction in the modern medicine with the proven safety for different diseases. But the effectiveness of this therapy is still under research. We believe that in most severe cases of a rapidly progressive interstitial lung disease the transplantation of mesenchymal stem cells may be an effective technology due to their immunomodulatory properties.

Official Title
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A Phase I-II Study to Evaluate Safety and Efficacy of Allogeneic Bone-Marrow Mesenchymal Stem Cells in Patients With Rapidly Progressive Interstitial Lung Disease

Conditions
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Idiopathic Interstitial Pneumonia, Interstitial Lung Disease, Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Bone marrow mesenchymal stem cells
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients 20-80 years old Diagnosis of idiopathic interstitial pneumonia or secondary to connective tissue diseases interstitial lung disease, based on: Clinical symptoms > 12 months duration, Histologically diagnosed or diagnostic chest HRCT features of interstitial pneumonia Forced Vital Capacity (FVC) ≥ 40% predicted and Diffusing Lung Capacity (DLCO) ≥20% Loss more than 10% of FVC (L) and DLCO during the last 12 months Signed informed consent. Exclusion Criteria: Diagnosis of an interstitial lung disease other than idiopathic interstitial pneumonia or connective tissue disease associated with interstitial lung disease (sarcoidosis, pulmonary alveolar proteinosis, lymphangioleiomyomatosis, pulmonary amyloidosis, exposure-related lung disease etc) Obstructive lung disease: FEV1/FVC < 0.70 Clinically significant medical condition, in the opinion of the investigator, may compromise the results of the study Evidence of active infection within 4 week prior to enrollment History of malignancy < 5 years prior to enrollment Unable to cooperate with any study procedures Pregnant or breast-feeding Treatment with antiinflammatory or antifibrotic drugs including oral steroids, cytostatic drugs, pirfenidone, D penicillamine, colchicine, tumor necrosis factor α blockers, imatinib, interferon γ, monoclonal antibodies < 6 months prior to randomization. Active listing for transplant of any organ. Known history of alcohol abuse within 1 year prior to enrollment Participation in another clinical trial

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSCs<br>2 intravenous infusions of suspension of 200 000 000 MSCs each at interval of 7 days. Infusions will be repeated every 3 months for 1 year. | Drug: Bone marrow mesenchymal stem cells<br>* Bone marrow will be harvested in healthy donors followed by separation and cultivation of MSCs. Before infusion cells will be suspended in 400 mL saline<br>|
| Placebo Comparator: placebo<br>2 intravenous infusions of 400 mL saline each at interval of 7 days. Infusions will be repeated every 3 months for 1 year. | Drug: Placebo<br>* intravenous infusion of 400 mL saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Number of serious adverse events | registration of adverse events related to infusion and 12 months follow-up | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLCO changes from baseline | Assessment of the diffusing lung capacity at 3, 6, 9, 12 months of treatment | 12 months | 
| FVC changes from baseline | Assessment of spirometry at 3, 6, 9, 12 months of treatment | 12 months | 
| exercise capacity changes | Assessment of 6MWD at 3, 6, 9, 12 months of treatment | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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interstitial lung disease, idiopathic interstitial pneumonia, idiopathic pulmonary fibrosis, stem cells