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

NCT05035862 | Terminated Phase 1 FDA Drug

• 2 other identifiers: STUDY000026552709
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Asthma

Keywords

Asthma

Outcome Measures

Primary Outcomes (2)

• 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-γ 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 γMSC 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)

• Number of grade ≥3 adverse reaction attributable to the γMSC product

  This outcome will measure toxicity. Toxicity is defined as any grade ≥3 adverse reaction and attributable to the γMSC 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 Outcomes (5)

• Change in lung function test

  Baseline, 7 to 30 days post-infusion (study day 14 to 37)

• In- vivo trafficking of MSCs after intravenous infusion

  7 to 30 days post-infusion (study day 14 to 37)

• Upper airway inflammation of MSC treatment

  7 to 30 days post-infusion (study day 14 to 37)

• Circulating inflammatory cells of MSC treatment

  7 to 30 days post-infusion (study day 14 to 37)

• Biophysical characteristics of the cell products and correlation with clinical outcome

  7 to 30 days post-infusion (study day 14 to 37)

Study Arms (1)

Infusion of γMSCs

EXPERIMENTAL

Escalating doses Dose escalation design with two dose levels. The low dose level involves a single intravenous infusion of γMSCs at 2x106 cells/kg. The high dose level involves a single intravenous infusion of γMSCs at 5x106 cells/kg.

Drug: Albuterol Sulfate; Drug: Interferon gamma-primed mesenchymal stromal cells (MSCs); Drug: Prednisone

Interventions

Albuterol Sulfate DRUG

Participants who experience symptoms of cough, dyspnea, chest tightness or wheezing will initiate use of albuterol (2 inhalations, 90 mcg/actuation) by metered dose inhaler (MDI) every 20 minutes for up to 1 hour and then every 4 hours if necessary.

Infusion of γMSCs

Interferon gamma-primed mesenchymal stromal cells (MSCs) DRUG

IFNγ-primed bone marrow MSCs at a dose level of 2x106 cells/kg and a dose level of 5x106 cells/kg

Also known as: Interferon gamma (IFNγ)-primed human bone marrow-derived mesenchymal stromal cells

Infusion of γMSCs

Prednisone DRUG

Prednisone is recommended if the participant uses more than 12 inhalations of albuterol in 24 hours (excluding preventive use before exercise), or if the patient has ongoing symptoms for 48 hours or longer. The recommended prednisone dose for acute exacerbations is 2 mg/kg/day (maximum 60 mg) as a single dose for two days followed by 1 mg/kg/day (maximum 30 mg) as a single dose for two days. All administered doses will be rounded down to the nearest 10 mg.

Infusion of γMSCs

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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\*
• 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

Sponsors & Collaborators

• Emory University: lead
• The Marcus Foundation: collaborator
• Ossium Health, Inc.: collaborator

Study Sites (1)

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Asthma

Interventions

Albuterol; Interferon-gamma; Prednisone

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Macrophage-Activating Factors; Lymphokines; Proteins; Biological Factors; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Edwin Horwitz, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: September 5, 2021
• Study Start: March 16, 2022
• Primary Completion: December 16, 2022
• Study Completion: December 16, 2022
• Last Updated: June 3, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 12 months after publication of the primary outcome manuscript.
• Access Criteria: Access will be limited to scientific investigators who wish to perform a secondary analysis of the data. These investigators must provide a written request and data analysis protocol for review by the Principal Investigator.

Locations

US (1)