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

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

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis; Interstitial Lung Disease; Idiopathic Interstitial Pneumonia
• Intervention / Treatment: Drug: Bone marrow mesenchymal stem cells; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115682
    • Federal Research Clinical Center FMBA of Russia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSCs; 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; 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
Placebo Comparator: placebo; 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; intravenous infusion of 400 mL saline

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Federal Research Clinical Center of Federal Medical & Biological Agency, Russia

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: November 1, 2015
• First Submitted That Met QC Criteria: November 2, 2015
• First Posted (Estimate): November 3, 2015

Study Record Updates

• Last Update Posted (Actual): January 9, 2018
• Last Update Submitted That Met QC Criteria: January 8, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: stem cells; interstitial lung disease; idiopathic interstitial pneumonia; idiopathic pulmonary fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Fibrosis; Lung Diseases; Pneumonia; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Idiopathic Interstitial Pneumonias; Hamman-Rich Syndrome
• Other Study ID Numbers: ILD-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No