NCT02866721

Safety and Tolerability Study of Allogeneic Mesenchymal Stem Cell Infusion in Adults With Cystic Fibrosis

A Phase I, Single Center, Open Label, Single Dose, Dose Escalation Study Assessing the Safety and Tolerability of AllogeneiC MEsenchymAl Stem CEll Infusion in Adults With Cystic Fibrosis-CEASE CF

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: University Hospitals Cleveland Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

This study is being done to test if it is safe to give stem cells to adult patients with Cystic Fibrosis (CF). The kind of stem cells we are studying are called allogeneic human mesenchymal stem cells or MSCs. MSCs are cells in the body that can grow into different types of cells and respond to various environmental situations. Allogeneic means the cells come from another person (a donor). This study is only looking at whether or not it is safe to give the stem cells to adults with CF and how the infusion is tolerated. In the future, other studies may be done to see if stem cells can be a new therapeutic treatment for CF. Stem cells, like other medical products that are intended to treat, cure or prevent disease, generally require approval from the U.S. Food and Drug Administration (FDA) before they can be marketed. The FDA has not approved any stem cell-based products for usual medical care, other than some specific blood forming stem cells for certain indications.

Detailed description

This will be a prospective, single-center, dose-escalation, open-label interventional study to evaluate the safety and tolerability of allogeneic human mesenchymal stem cells (hMSCs) in 15 clinically stable subjects with cystic fibrosis (CF) age ≥ 18 years. After a two to six week screening period, subjects will have a Baseline visit (Days 1-2) where they will undergo a single intravenous infusion of up to 5 x 10E6 allogeneic hMSCs/kilogram (hMSCs/kg) of body weight. Infusions will be performed in the Dahms Clinical Research Unit (DCRU) of University Hospitals Cleveland Medical Center. Subjects will be monitored for any infusion related toxicities for 24 hours after the infusion. Subsequent study visits will occur on Days 7, 14, 28, Months 3 and 6 and telephone calls will occur on Days 4 (or 5), 21, 56 and Month 12. Subject safety and tolerability of a single dose of hMSCs will be evaluated at study visits by review of subject diaries, interval history, pulmonary exacerbations, physical examination, spirometry, and analysis of safety laboratories. Special attention will be placed upon detecting pulmonary exacerbations because anti-inflammatory therapies theoretically could suppress the immune system to the point where it leads to increased infectious complications, although MSC therapeutics are proposed to be antimicrobial. In addition to evaluating safety, this study will also explore efficacy end-points for future clinical trials of MSCs in CF including inflammatory biomarkers from blood and sputum. Serum markers (calprotectin, myeloperoxidase (MPO), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1β (IL-1β), IL-6, IL8, IL-17, and tumor necrosis factor-a (TNF-a) and sputum markers (white cell counts and differentials, IL-1β, IL-6, IL-8, IL-10, IL-17, GM-CSF, macrophage inflammatory protein-3a (MIP- 3a), TNF-a, and active proteases including neutrophil elastase, alpha-1-antitrypsin, and matrix metallopeptidase 9 (MMP-9) will be determined at Baseline and on Days 7 and 28 for with-in subject comparison. All subject samples will be archived for future projects. Finally, a diagnostic bone marrow exam will be performed on subjects with CF who consent to undergo this optional procedure. Bone marrow samples will be banked and used for future translational studies.

Conditions

• Cystic Fibrosis

Interventions

Type	Name	Description
BIOLOGICAL	Mesenchymal Stem Cells	A single dose, one time infusion (in the vein) of one of the following doses of human mesenchymal stem cells (hMSCs): 1 x 10\^6, 3 x 10\^6 or 5 x 10\^6 human mesenchymal stem cells per kilogram body weight (hMSCs/kg) during Visit 2. A traditional 3+3 design will be utilized. Allogeneic mesenchymal stem cells (MSCs) will be derived from bone marrow aspirates from a healthy donor whose serum tests negative for cytomegalovirus (CMV) antibodies. Healthy donors will undergo tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the MSCs will be validated for in vitro and in vivo efficacy and potency using the in vivo murine pre-clinical model of cystic fibrosis lung infection and inflammation.

Timeline

• Start date: 2016-08-01
• Primary completion: 2020-08-01
• Completion: 2020-08-01
• First posted: 2016-08-15
• Last updated: 2023-01-30
• Results posted: 2023-01-30

Locations

1 site across 1 country: United States