Mechanisms of Interferon Gamma-primed Mesenchymal Stromal Cells (MSCs) for Moderate-to-severe Persistent Asthma

• Status: Recruiting
• Trial end date: 2023-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Emory University
• Collaborator: The Marcus Foundation
• Treatments: Albuterol; Interferon-gamma; Interferons; Prednisone

Criteria

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 γMSC 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*

• Receiving treatment with biologics (i.e., omalizumab, mepolizumab) within 3 months prior to the screening visit*

• 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 γMSC 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.