Allogeneic Human Cells (hMSC) Via Intravenous Delivery in Patients With Mild Asthma

Study Overview
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Brief Summary
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A Phase 1 investigation will be performed to test the safety of two doses of bone marrow-derived MSCs (20,000,000 and 100,000,000) administered via peripheral intravenous infusion.

Detailed Description
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A Phase 1 investigation will be performed to test the safety of two doses of bone marrow-derived MSCs (20,000,000 and 100,000,000) administered via peripheralintravenous infusion. Group 1: 3 subjects will receive a single administration of allogeneic hMSCs: 20 million cells delivered via peripheral intravenous infusion Group 2: 3 subjects will receive a single administration of allogeneic hMSCs: 100 million cells delivered via peripheral intravenous infusion Interim safety analysis will be performed four weeks after the 1st subject is enrolled in each cohort. Continued safety and tolerability with review of adverse events (AEs) will be assessed at each visit. Efficacy parameters (pulmonary function tests, diffusing capacity (DLCO), lung volumes, 6-minute walk test (6MWT), and dyspnea/quality of life [QOL] questionnaires) will be assessed every 12 weeks until study completion. Clinical laboratory tests to assess safety will be performed at every visit.

Official Title
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A Phase I, Trial to Evaluate the Safety, Tolerability, and Potential Efficacy of Allogeneic Human Mesenchymal Stem Cell Infusion in Patients With Mild Asthma

Conditions
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Asthma

Intervention / Treatment
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* Biological: hMSCs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent be between 18 and 65 years at the time of signing the Informed Consent have a clinical diagnosis of asthma prior to screening in accordance with the guidelines of the American Thoracic Society/European Respiratory Society ACQ over 1.25 have a smoking history of less than 10 pack-years total and have not been smoking for at least the last 12 months Perform a positive methacholine challenge at screening and repeat positive methacholine challenge at baseline visit (14 days later) Have normal or mild obstructive spirometry Have normal right heart function as documented by Doppler echo or right heart catheterization If female, be surgically sterile, post-menopausal (more than 1 year), or practice double barrier methods of birth control Subjects may receive non-drug therapies including oxygen supplementation no greater than 2L/minute, and pulmonary rehabilitation Subjects may be on standard of care asthma medications including inhaled corticosteroids-long acting beta agonist at a dose not greater than 1 mg of a fluticasone equivalent Exclusion Criteria: Have any active infection that is not treated Be unable to perform any of the assessments required for endpoint analysis. currently receive (or have received within four weeks of screening) experimental agents for the treatment of asthma be actively listed (or expecting to be listed in the near future) for transplant of any organ Have clinically important abnormal screening laboratory values : blood screening tests (Hematology, Chemistry, CBC including Eosinophil count) results that are not within normal limits (according to UMHC Laboratory Reference Ranges) Have a serious comorbid illness that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study Have known allergies to penicillin or streptomycin Be an organ transplant recipient Have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma Have a non-pulmonary condition that limits lifespan to less than a year. Have a history of drug or alcohol abuse within the past 24 months. Be serum positive for HIV, hepatitis BsAg or Viremia hepatitis C Be currently participating (or have participated within the previous 30 days) in an investigational therapeutic or device trial. Have hypersensitivity to dimethyl sulfoxide (DMSO) Have a resting oxygen saturation (SpO2) on room air of more than 93% at sea level or more than 88% at an altitude above 5,000 feet above sea level (1524 meters)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: a first group of 3 patients will receive a lower dose of 20 million hMSCs, followed by a second group of 3 patients to receive a dose of 100 million hMSCs
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group receiving 20 million hMSCs<br>3 patients will receive a single administration of allogeneic hMSCs: 20 x106 (20 million) cells delivered via peripheral intravenous infusion | Biological: hMSCs<br>* intravenous infusion of bone marrow-derived allogeneic stem cells<br>* Other names: allogeneic mesenchymal stem cell;|
| Experimental: Group receiving 100 million hMSCs<br>3 patients will receive a single administration of allogeneic hMSCs: 1 x108 (100 million) cells delivered via peripheral intravenous infusion | Biological: hMSCs<br>* intravenous infusion of bone marrow-derived allogeneic stem cells<br>* Other names: allogeneic mesenchymal stem cell;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participant with treatment emergent serious adverse events | as defined as the incidence of any treatment-emergent serious adverse events; these are a composite of death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities | Week 4 post infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in lung function | Difference in FEV1 Variability in morning peak expiratory flow measurements Difference in frequency of acute exacerbations defined as: hospitalizations, missed work days, and/or oral steroids for more than 3 days Decrease in fractional excretion of inhaled NO (FENO; less than 50 ppb) | Participants will be followed from 1 week to an expected average of 48 weeks following infusion | 
| Decrease in peripheral eosinophilia | Decrease in number of peripheral eosinophils | Participants will be followed from 1 week to an expected average of 48 weeks following infusion | 
| Difference in subject reported dyspnea and quality of life assessments | Difference in subject reported dyspnea and quality of life assessments: Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) | Participants will be followed from 1 week to an expected average of 48 weeks following infusion | 
| Death from any cause | Death from any cause | Participants will be followed from 1 week to an expected average of 48 weeks following infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stem cell, mesenchymal stem cell, lung, asthma