Asthma Clinical Trial
Official title:
A Phase 1 Study to Evaluate Safety, Toxicity, and Potential Mechanisms of Interferon Gamma-primed Mesenchymal Stromal Cells (MSCs) for Moderate-to-severe Persistent Asthma
This study is a two strata, dose escalation Phase I clinical trial designed to assess the safety and determine the maximal tolerated dose (MTD) of allogenic cord tissue derived MSCs (cMSCs, stratum 1) and allogeneic, interferon-γ primed bone marrow MSCs (γMSCs, stratum 2). Each stratum is designed to independently accrue 3 children at a dose level 1 of 2x106 cells/kg and 6 children at dose level 2 of 10x106 cells/kg, resulting in 9 children in each stratum. The primary objectives are to determine the safety and toxicity of allogeneic cord tissue derived MSCs and allogeneic interferon-γ primed bone marrow derived MSCs.
Status | Recruiting |
Enrollment | 12 |
Est. completion date | December 2025 |
Est. primary completion date | July 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 30 Years |
Eligibility | Inclusion Criteria: - Age 18 through 30 years at the screening visit - Physician diagnosis of asthma - Onset of asthma during childhood - Evidence of atopy, evidenced by allergic rhinitis, aeroallergen sensitization, elevated total immunoglobulin E (IgE) level based on age-dependent reference values, or blood eosinophil counts > or = 150 cells/microliter - Moderate-to-severe persistent asthma as defined by the National Asthma Education and Prevention Program Expert Panel Report-4 Exclusion criteria at the screening visit include any of the following (*may be re-enrolled): - A Panel Reactive Antibodies (PRA) test is positive for human leukocyte antigens (HLA) antibodies against the ?MSC product - Oral or injectable corticosteroid use within the two-week period prior to the screening visit.* Nasal corticosteroids may be used at any time during this trial at the discretion of the study's Medical Principal Investigator. - Use of medications known to significantly interact with corticosteroid disposition within the two-week period prior to the screening visit, including but not limited to carbamazepine, erythromycin or other macrolide antibiotics, phenobarbital, phenytoin, rifampin, and ketoconazole* - Presence of chronic or active lung disease other than asthma, including disorders of the airways or chest wall - Current smoking or vaping - History of premature birth before 35 weeks gestation - Significant medical illness other than asthma, including thyroid disease, diabetes mellitus, sickle cell disease, Cushing's disease, Addison's disease, hepatic disease, immune deficiency, or concurrent medical problems that could require oral corticosteroids during the study or that would place the subject at increased risk of participating in the study - A history of cataracts, glaucoma, or any other medical disorder associated with an adverse effect to corticosteroids - History of adverse reactions to corticosteroids or short-acting bronchodilators or any of their ingredients - Receiving allergen immunotherapy other than an established maintenance regimen (continuous regimen for = 3 months)* - Pregnancy or lactation - If the participant is a female, failure to practice abstinence or use of an acceptable birth control method - Inability to perform study procedures - Current participation in another investigational drug trial - Evidence that the participant may be unreliable or nonadherent, or may move from the clinical center area before trial completion Exclusion criteria at the randomization/infusion visit include any of the following: - Clinically significant deterioration in the level of asthma control, evidenced by: - Decrease in post-bronchodilator forced expiratory volume in one second (FEV1) of 15% (absolute change) compared to the post-bronchodilator FEV1 value obtained at the baseline visit, or - An asthma exacerbation - Clinically significant thrombocytopenia, anemia, neutropenia or elevations in the white blood cell count, assessed at the screening visit - Positive pregnancy test The investigators will also ask participants to refrain from receiving new asthma therapies such as biologics until the final safety determination is made 7 days after the ?MSC infusion (at study Day 14). They will also ask participants to refrain from participating in other interventional drug studies for the duration of their participation. |
Country | Name | City | State |
---|---|---|---|
United States | Children's Healthcare of Atlanta | Atlanta | Georgia |
Lead Sponsor | Collaborator |
---|---|
Emory University | Ossium Health, Inc., The Marcus Foundation |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in number of adverse events and severe adverse events post-intervention | This outcome will measure safety of allogeneic cord tissue derived MSCs and allogeneic interferon-? primed bone marrow derived MSCs. Assessments will be made by physical examination and further investigation as indicated. Events will be classified according to the NIH Clinical Toxicity Criteria for Adverse Events (CTCAE), version 5. All recorded adverse events and serious adverse events will be documented and recorded. Their attribution to the ?MSC product will be determined. Adverse events that may be attributable to the study product include dyspnea, cough, wheezing, respiratory failure, allergic reaction, anaphylaxis, and infusion-related reaction. | During the infusion, during the observation interval after the infusion (2 hours postinfusion), one day after the infusion, and at 7 to 30 days after the infusion (study day 14 to 37) | |
Primary | Number of grade =3 adverse reaction attributable to the ?MSC product | This outcome will measure toxicity. Toxicity is defined as any grade =3 adverse reaction and attributable to the ?MSC product (attribution listed as at least probable), occurring from MSC infusion (at study day 7) through 7 days post-infusion (study day 14). Toxicity is considered unacceptable. | 7 to 30 days post-infusion (study day 14 to 37) | |
Secondary | Change in lung function test | Change in lung function test and asthma characterization will determine the clinical impact of MSC therapy | Baseline, 7 to 30 days post-infusion (study day 14 to 37) | |
Secondary | In- vivo trafficking of MSCs after intravenous infusion | In vivo trafficking of MSCs after intravenous infusion | 7 to 30 days post-infusion (study day 14 to 37) | |
Secondary | Upper airway inflammation of MSC treatment | Upper airway inflammation will be determined by analysis of small molecule inflammatory constituents in exhaled breath condensate. | 7 to 30 days post-infusion (study day 14 to 37) | |
Secondary | Circulating inflammatory cells of MSC treatment | Circulating cell inflammation will be determined by flow cytometric analysis of peripheral blood cells and AbSeq analysis of peripheral blood cells. | 7 to 30 days post-infusion (study day 14 to 37) | |
Secondary | Biophysical characteristics of the cell products and correlation with clinical outcome | Characteristics of the ?MSCs will be determined by comprehensive analysis at the Marcus Center for Therapeutic Cell Characterization and Manufacturing (MC3M) | 7 to 30 days post-infusion (study day 14 to 37) |
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