Asthma
Conditions
Keywords
stem cell, mesenchymal stem cell, lung, asthma
Brief summary
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
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.
Interventions
BIOLOGICALhMSCs
intravenous infusion of bone marrow-derived allogeneic stem cells
Sponsors
The Marcus Foundation
Marilyn Glassberg
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participant with treatment emergent serious adverse events | Week 4 post infusion | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in lung function | Participants will be followed from 1 week to an expected average of 48 weeks following infusion | 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) |
| Decrease in peripheral eosinophilia | Participants will be followed from 1 week to an expected average of 48 weeks following infusion | Decrease in number of peripheral eosinophils |
| Difference in subject reported dyspnea and quality of life assessments | 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: Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) |
| Death from any cause | Participants will be followed from 1 week to an expected average of 48 weeks following infusion | Death from any cause |
Countries
United States
Outcome results
None listed