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| ID | Type | Description | Link |
|---|---|---|---|
| DASENB15A0 | Other Grant/Funding Number | Cystic Fibrosis Foundation Therapeutics |
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| Name | Class |
|---|---|
| Case Western Reserve University | OTHER |
| Cystic Fibrosis Foundation | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Human Allogeneic Mesenchymal Stem Cells | Experimental | One time intravenous (IV) Infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram of body weight (hMSCs/kg). A dose escalation using the "3+3" design will be employed. The three doses are 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There is no placebo group. All study participants will receive stem cells. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mesenchymal Stem Cells | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With a Dose Limiting Toxicity (DLT), Triggered by Occurrence in the First 24 Hours After Human Mesenchymal Stem Cell (hMSC) Infusion of Grade ≥3 Infusion-related Allergic Toxicities | For this study, dose limiting toxicities included the emergence of infusion-related allergic adverse events as well as regimen related toxicities in the first 24 hours after hMSC infusion of a grade ≥ 3 as scored according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. This is the number of participants who experienced a dose limiting toxicity during the study. | 24 hours post infusion |
| Number of Serious Adverse Events and Number of Non-Serious Adverse Events | Participants were followed for 12 months after human mesenchymal stem cell infusion. All events from the infusion date through the end of follow-up were included. This shows the total number of adverse events or serious adverse events occurring in each dosing cohort. | 1 year |
| Number of Pulmonary Exacerbations Requiring Intravenous Antibiotics | Participants were followed for 12 months after human mesenchymal stem cell infusion. All events occurring from the infusion date through the end of follow-up were included. This shows the number of pulmonary exacerbations requiring intravenous antibiotics in each dosing cohort. | 1 year |
| Forced Expiratory Volume in the First Second (FEV1) % Predicted at Baseline and 30 Minutes, 4 Hours, 24 Hours, 7 Days, 14 Days, 28 Days, 3 Months, 6 Months Post Human Mesenchymal Stem Cell Infusion. | Lung function was followed for 6 months post human mesenchymal stem cell infusion. This shows the mean forced expiratory volume in the first second (FEV1) percent predicted for each cohort throughout the study. | Baseline and 30 minutes, 4 hours, 24 hours, 7 days, 14 days, 28 days, 3 months, 6 months Post Human Mesenchymal Stem Cell Infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Inflammatory Markers - Calportectin Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including Calprotectin were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for calportectin was 88.3 picogram per millilitre. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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Cystic Fibrosis (CF) Subject Inclusion Criteria:
Male or female ≥18 years of age
Confirmed diagnosis of CF as evidenced by 1 or more clinical features consistent with the CF phenotype and 1 or more of the following criteria:
Clinically stable with no significant changes in health status within 2 weeks prior to screening.
Forced expiratory volume in the first second (FEV1) ≥ 40% predicted for age based on the global lung function initiative equations at the screening visit
Weight ≥ 40 kilograms at the screening visit
Able to perform repeatable, consistent efforts in pulmonary function testing
Written informed consent obtained from the subject.
CF Subject Exclusion Criteria:
Inclusion Criteria for Healthy Volunteer Donors (NOTE: Enrollment for Healthy Volunteers is closed):
Inclusion Criteria for CF Donors:
1. CF subject enrolled in the main study and consented to this optional procedure
Exclusion Criteria for both Healthy Volunteer (HV) Donors and CF Donors:
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| Name | Affiliation | Role |
|---|---|---|
| Erica A. Roesch, MD | University Hospitals Cleveland Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospitals Cleveland Medical Center | Cleveland | Ohio | 44106 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20215542 | Background | Ivy SP, Siu LL, Garrett-Mayer E, Rubinstein L. Approaches to phase 1 clinical trial design focused on safety, efficiency, and selected patient populations: a report from the clinical trial design task force of the national cancer institute investigational drug steering committee. Clin Cancer Res. 2010 Mar 15;16(6):1726-36. doi: 10.1158/1078-0432.CCR-09-1961. Epub 2010 Mar 9. | |
| 23992090 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 1 x 10^6 Human Allogeneic Mesenchymal Stem Cells Per Kilogram | One time intravenous infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram body weight (hMSCs/kg). A dose escalation using the "3+3" design was employed. The three doses were 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There was no placebo group. All study participants received stem cells. Mesenchymal Stem Cells: A single dose, one time infusion (in the vein) of one of the following doses of hMSCs: 1 x 10^6, 3 x 10^6 or 5 x 10^6 hMSCs/kg body weight during Visit 2. A traditional 3+3 design was utilized. Allogeneic MSCs were derived from bone marrow aspirates from a healthy donor whose serum tested negative for cytomegalovirus (CMV) antibodies. The healthy donor underwent tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the mesenchymal stem cells (MSCs) were validated for in vitro and in vivo efficacy and potency using the in vivo murine pre-clinical model of cystic fibrosis (CF) lung infection and inflammation. |
| FG001 | 3 x 10^6 Human Allogeneic Mesenchymal Stem Cells Per Kilogram | One time intravenous infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram body weight (hMSCs/kg). A dose escalation using the "3+3" design was employed. The three doses were 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There was no placebo group. All study participants received stem cells. Mesenchymal Stem Cells: A single dose, one time infusion (in the vein) of one of the following doses of hMSCs: 1 x 10^6, 3 x 10^6 or 5 x 10^6 hMSCs/kg body weight during Visit 2. A traditional 3+3 design was utilized. Allogeneic MSCs were derived from bone marrow aspirates from a healthy donor whose serum tested negative for cytomegalovirus (CMV) antibodies. The healthy donor underwent tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the mesenchymal stem cells (MSCs) were validated for in vitro and in vivo efficacy and potency using the in vivo murine pre-clinical model of cystic fibrosis (CF) lung infection and inflammation. |
| FG002 | 5 x 10^6 Human Allogeneic Mesenchymal Stem Cells Per Kilogram | One time intravenous infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram body weight (hMSCs/kg). A dose escalation using the "3+3" design was employed. The three doses were 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There was no placebo group. All study participants received stem cells. Mesenchymal Stem Cells: A single dose, one time infusion (in the vein) of one of the following doses of hMSCs: 1 x 10^6, 3 x 10^6 or 5 x 10^6 hMSCs/kg body weight during Visit 2. A traditional 3+3 design was utilized. Allogeneic MSCs were derived from bone marrow aspirates from a healthy donor whose serum tested negative for cytomegalovirus (CMV) antibodies. The healthy donor underwent tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the mesenchymal stem cells (MSCs) were validated for in vitro and in vivo efficacy and potency using the in vivo murine pre-clinical model of cystic fibrosis (CF) lung infection and inflammation. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 1 x 10^6 Human Allogeneic Mesenchymal Stem Cells Per Kilogram | One time intravenous Infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram body weight (hMSCs/kg). A dose escalation using the "3+3" design was employed. The three doses were 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There was no placebo group. All study participants received stem cells. Mesenchymal Stem Cells (MSCs): A single dose, one time infusion (in the vein) of one of the following doses of hMSCs: 1 x 10^6, 3 x 10^6 or 5 x 10^6 hMSCs/kg body weight during Visit 2. A traditional 3+3 design was utilized. Allogeneic MSCs were derived from bone marrow aspirates from a healthy donor whose serum tested negative for cytomegalovirus (CMV) antibodies. The healthy donor underwent tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the MSCs were validated for in vitro and in vivo efficacy and potency using the in vivo murine pre-clinical model of cystic fibrosis (CF) lung infection and inflammation. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With a Dose Limiting Toxicity (DLT), Triggered by Occurrence in the First 24 Hours After Human Mesenchymal Stem Cell (hMSC) Infusion of Grade ≥3 Infusion-related Allergic Toxicities | For this study, dose limiting toxicities included the emergence of infusion-related allergic adverse events as well as regimen related toxicities in the first 24 hours after hMSC infusion of a grade ≥ 3 as scored according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. This is the number of participants who experienced a dose limiting toxicity during the study. | Number of participants with a dose limiting toxicity. All subjects receiving the human mesenchymal stem cell infusing were included. | Posted | Count of Participants | Participants | 24 hours post infusion |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1 x 10^6 Human Allogeneic Mesenchymal Stem Cells Per Kilogram | One time intravenouos infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram body weight (hMSCs/kg). A dose escalation using the "3+3" design was employed. The three doses were 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There was no placebo group. All study participants received stem cells. Mesenchymal Stem Cells (MSCs): A single dose, one time infusion (in the vein) of one of the following doses of hMSCs: 1 x 10^6, 3 x 10^6 or 5 x 10^6 hMSCs/kg body weight during Visit 2. A traditional 3+3 design was utilized. Allogeneic MSCs were derived from bone marrow aspirates from a healthy donor whose serum tested negative for cytomegalovirus (CMV) antibodies. The healthy donor underwent tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the MSCs were 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cystic Fibrosis Pulmonary Exacerbation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Pulmonary exacerbation requiring hospital admission for IV antibiotics. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Right leg pain | Vascular disorders | Systematic Assessment |
Limitations include the small sample size and short study period. The primary objective was to determine safety, therefore therapeutic exposure was limited to a single dose of human mesenchymal stem cells (hMSCs). The clinical trial was not powered to detect changes in secondary exploratory measures, thus limiting our understanding of the impact of hMSCs on inflammation in cystic fibrosis. The ability to assess efficacy was further limited by the inability of participants to produce sputum.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Erica Roesch, MD | University Hospitals, Rainbow Babies and Children's Hospital | (216) 844-3267 | Erica.Roesch@UHHospitals.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 17, 2019 | Jan 13, 2022 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 3, 2020 | Jan 13, 2022 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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|
| Serum Inflammatory Markers - Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for GM-CSF was 2.6 picograms per milliliter. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Serum Inflammatory Markers - Interleukin-1 (IL-1) Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including interleukin -1 (IL-1) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for IL-1 was 13.1 picograms per milliliter. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Serum Inflammatory Markers - Interleukin-17 (IL-17) Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including interleukin -17 (IL-17) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for IL-17 was 13.5 picograms per milliliter. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Serum Inflammatory Markers - Interleukin-6 (IL-6) Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including interleukin -6 (IL-6) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for IL-6 was 13.5 picograms per milliliter. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Serum Inflammatory Markers - Interleukin-8 (IL-8) Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including interleukin -8 (IL-8) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for IL-8 was 13.9 picograms per milliliter. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Serum Inflammatory Markers - Myeloperoxidase (MPO) Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including myeloperoxidase (MPO) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Serum Inflammatory Markers - Tumor Necrosis Factor Alpha (TNF-a) Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including tumor necrosis factor alpha (TNF-a) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit of detection for TNF-a was 12.9 picograms per millilter. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Sputum Inflammatory Markers - Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including granulocyte-macrophage colony-stimulating factor (GM-CSF) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Sputum Inflammatory Markers - Interleukin-1 (IL-1) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including interleukin-1 (IL-1) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Sputum Inflammatory Markers - Interleukin-10 (IL-10) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including interleukin-10 (IL-10) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Sputum Inflammatory Markers - Interleukin-17 (IL-17) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including interleukin-17 (IL-17) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Sputum Inflammatory Markers - Interleukin-6 (IL-6) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including interleukin-6 (IL-6) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Sputum Inflammatory Markers - Interleukin-8 (IL-8) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including interleukin-8 (IL-8) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Sputum Inflammatory Markers - Macrophage Inflammatory Protein-3 Alpha (MIP-3a) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including macrophage inflammatory protein-3 alpha (MIP-3a) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Sputum Inflammatory Markers - Tumor Necrosis Factor Alpha (TNF-a) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including tumor necrosis factor alpha (TNF-a) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
| Background |
| Inamdar AC, Inamdar AA. Mesenchymal stem cell therapy in lung disorders: pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell. Exp Lung Res. 2013 Oct;39(8):315-27. doi: 10.3109/01902148.2013.816803. Epub 2013 Aug 30. |
| 22118960 | Background | Gebler A, Zabel O, Seliger B. The immunomodulatory capacity of mesenchymal stem cells. Trends Mol Med. 2012 Feb;18(2):128-34. doi: 10.1016/j.molmed.2011.10.004. Epub 2011 Nov 25. |
| 23133515 | Background | Lalu MM, McIntyre L, Pugliese C, Fergusson D, Winston BW, Marshall JC, Granton J, Stewart DJ; Canadian Critical Care Trials Group. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS One. 2012;7(10):e47559. doi: 10.1371/journal.pone.0047559. Epub 2012 Oct 25. |
| 19023885 | Background | Caplan AI. Why are MSCs therapeutic? New data: new insight. J Pathol. 2009 Jan;217(2):318-24. doi: 10.1002/path.2469. |
| 20423678 | Background | Bonfield TL, Caplan AI. Adult mesenchymal stem cells: an innovative therapeutic for lung diseases. Discov Med. 2010 Apr;9(47):337-45. |
| 24027567 | Background | Dimarino AM, Caplan AI, Bonfield TL. Mesenchymal stem cells in tissue repair. Front Immunol. 2013 Sep 4;4:201. doi: 10.3389/fimmu.2013.00201. |
| 24515922 | Background | Antunes MA, Laffey JG, Pelosi P, Rocco PR. Mesenchymal stem cell trials for pulmonary diseases. J Cell Biochem. 2014 Jun;115(6):1023-32. doi: 10.1002/jcb.24783. |
| 17641052 | Result | Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol. 2007 Aug 1;179(3):1855-63. doi: 10.4049/jimmunol.179.3.1855. |
| 26925108 | Result | Sutton MT, Fletcher D, Ghosh SK, Weinberg A, van Heeckeren R, Kaur S, Sadeghi Z, Hijaz A, Reese J, Lazarus HM, Lennon DP, Caplan AI, Bonfield TL. Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment. Stem Cells Int. 2016;2016:5303048. doi: 10.1155/2016/5303048. Epub 2016 Jan 26. |
| BG001 | 3 x 10^6 Human Allogeneic Mesenchymal Stem Cells Per Kilogram | One time intravenous Infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram body weight (hMSCs/kg). A dose escalation using the "3+3" design was employed. The three doses were 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There was no placebo group. All study participants received stem cells. Mesenchymal Stem Cells (MSCs): A single dose, one time infusion (in the vein) of one of the following doses of hMSCs: 1 x 10^6, 3 x 10^6 or 5 x 10^6 hMSCs/kg body weight during Visit 2. A traditional 3+3 design was utilized. Allogeneic MSCs were derived from bone marrow aspirates from a healthy donor whose serum tested negative for cytomegalovirus (CMV) antibodies. The healthy donor underwent tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the MSCs were validated for in vitro and in vivo efficacy and potency using the in vivo murine pre-clinical model of cystic fibrosis (CF) lung infection and inflammation. |
| BG002 | 5 x 10^6 Human Allogeneic Mesenchymal Stem Cells Per Kilogram | One time intravenous Infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram body weight (hMSCs/kg). A dose escalation using the "3+3" design was employed. The three doses were 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There was no placebo group. All study participants received stem cells. Mesenchymal Stem Cells (MSCs): A single dose, one time infusion (in the vein) of one of the following doses of hMSCs: 1 x 10^6, 3 x 10^6 or 5 x 10^6 hMSCs/kg body weight during Visit 2. A traditional 3+3 design was utilized. Allogeneic MSCs were derived from bone marrow aspirates from a healthy donor whose serum tested negative for cytomegalovirus (CMV) antibodies. The healthy donor underwent tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the MSCs were validated for in vitro and in vivo efficacy and potency using the in vivo murine pre-clinical model of cystic fibrosis (CF) lung infection and inflammation. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Genotype | Number of individuals with two copies of the F508del mutation (F508del homozygous), one copy of the F508del mutation with a different cystic fibrosis causing mutation on the other allele (F508del heterozygous), or two cystic fibrosis causing mutations other than the F508del mutation (other). | Count of Participants | Participants |
|
| Forced Expiratory Volume in the first second (FEV1) % Predicted Distribution | Number of individuals with a Forced Expiratory Volume in the first second (FEV1) percent predicted of less than 70% predicted, between 70-84% predicted, or greater than or equal to 85% predicted. Percent predicted determined using the global lung initiative (GLI). Decreases in FEV1 are associated with more advanced cystic fibrosis lung disease. | Count of Participants | Participants |
|
| Sweat Chloride at Diagnosis | Mean | Standard Deviation | mmol/L |
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| Height | Mean | Standard Deviation | cm |
|
| Weight | Mean | Standard Deviation | kg |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
One time intravenouos Infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram body weight (hMSCs/kg). A dose escalation using the "3+3" design was employed. The three doses were 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There was no placebo group. All study participants received stem cells.
Mesenchymal Stem Cells (MSCs): A single dose, one time infusion (in the vein) of one of the following doses of hMSCs: 1 x 10^6, 3 x 10^6 or 5 x 10^6 hMSCs/kg body weight during Visit 2. A traditional 3+3 design was utilized.
Allogeneic MSCs were derived from bone marrow aspirates from a healthy donor whose serum tested negative for cytomegalovirus (CMV) antibodies. The healthy donor underwent tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the MSCs were 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.
| OG001 | 3 x 10^6 Human Allogeneic Mesenchymal Stem Cells Per Kilogram | One time intravenouos Infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram body weight (hMSCs/kg). A dose escalation using the "3+3" design was employed. The three doses were 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There was no placebo group. All study participants received stem cells. Mesenchymal Stem Cells (MSCs): A single dose, one time infusion (in the vein) of one of the following doses of hMSCs: 1 x 10^6, 3 x 10^6 or 5 x 10^6 hMSCs/kg body weight during Visit 2. A traditional 3+3 design was utilized. Allogeneic MSCs were derived from bone marrow aspirates from a healthy donor whose serum tested negative for cytomegalovirus (CMV) antibodies. The healthy donor underwent tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the MSCs were 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. |
| OG002 | 5 x 10^6 Human Allogeneic Mesenchymal Stem Cells Per Kilogram | One time intravenouos Infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram body weight (hMSCs/kg). A dose escalation using the "3+3" design was employed. The three doses were 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There was no placebo group. All study participants received stem cells. Mesenchymal Stem Cells (MSCs): A single dose, one time infusion (in the vein) of one of the following doses of hMSCs: 1 x 10^6, 3 x 10^6 or 5 x 10^6 hMSCs/kg body weight during Visit 2. A traditional 3+3 design was utilized. Allogeneic MSCs were derived from bone marrow aspirates from a healthy donor whose serum tested negative for cytomegalovirus (CMV) antibodies. The healthy donor underwent tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the MSCs were 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. |
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| Primary | Number of Serious Adverse Events and Number of Non-Serious Adverse Events | Participants were followed for 12 months after human mesenchymal stem cell infusion. All events from the infusion date through the end of follow-up were included. This shows the total number of adverse events or serious adverse events occurring in each dosing cohort. | All subjects who received human mesenchymal stem cells were included in the analysis. | Posted | Number | number of adverse events | 1 year |
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| Primary | Number of Pulmonary Exacerbations Requiring Intravenous Antibiotics | Participants were followed for 12 months after human mesenchymal stem cell infusion. All events occurring from the infusion date through the end of follow-up were included. This shows the number of pulmonary exacerbations requiring intravenous antibiotics in each dosing cohort. | All subjects who received human mesenchymal stem cells were included in the analysis. | Posted | Number | pulmonary exacerbations | 1 year |
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| Primary | Forced Expiratory Volume in the First Second (FEV1) % Predicted at Baseline and 30 Minutes, 4 Hours, 24 Hours, 7 Days, 14 Days, 28 Days, 3 Months, 6 Months Post Human Mesenchymal Stem Cell Infusion. | Lung function was followed for 6 months post human mesenchymal stem cell infusion. This shows the mean forced expiratory volume in the first second (FEV1) percent predicted for each cohort throughout the study. | All subjects who received human mesenchymal stem cells were included in the analysis. | Posted | Mean | Standard Deviation | FEV1 percent predicted | Baseline and 30 minutes, 4 hours, 24 hours, 7 days, 14 days, 28 days, 3 months, 6 months Post Human Mesenchymal Stem Cell Infusion |
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| Secondary | Serum Inflammatory Markers - Calportectin Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including Calprotectin were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for calportectin was 88.3 picogram per millilitre. | All subjects who received human mesenchymal stem cells were included in the analysis. | Posted | Mean | Standard Deviation | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Serum Inflammatory Markers - Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for GM-CSF was 2.6 picograms per milliliter. | All subjects who received human mesenchymal stem cells were included in the analysis. | Posted | Mean | Standard Deviation | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Serum Inflammatory Markers - Interleukin-1 (IL-1) Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including interleukin -1 (IL-1) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for IL-1 was 13.1 picograms per milliliter. | All subjects who received human mesenchymal stem cells were included in the analysis. | Posted | Mean | Standard Deviation | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Serum Inflammatory Markers - Interleukin-17 (IL-17) Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including interleukin -17 (IL-17) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for IL-17 was 13.5 picograms per milliliter. | All subjects who received human mesenchymal stem cells were included in the analysis. | Posted | Mean | Standard Deviation | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Serum Inflammatory Markers - Interleukin-6 (IL-6) Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including interleukin -6 (IL-6) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for IL-6 was 13.5 picograms per milliliter. | All subjects who received human mesenchymal stem cells were included in the analysis. | Posted | Mean | Standard Deviation | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Serum Inflammatory Markers - Interleukin-8 (IL-8) Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including interleukin -8 (IL-8) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit for detection for IL-8 was 13.9 picograms per milliliter. | All subjects who received human mesenchymal stem cells were included in the analysis. | Posted | Mean | Standard Deviation | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Serum Inflammatory Markers - Myeloperoxidase (MPO) Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including myeloperoxidase (MPO) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. | All subjects who received human mesenchymal stem cells were included in the analysis. | Posted | Mean | Standard Deviation | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Serum Inflammatory Markers - Tumor Necrosis Factor Alpha (TNF-a) Measurements at Baseline, Day 7, and Day 28 | Serum inflammatory markers including tumor necrosis factor alpha (TNF-a) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with standard deviation are shown. The lower limit of detection for TNF-a was 12.9 picograms per millilter. | All subjects who received human mesenchymal stem cells were included in the analysis. | Posted | Mean | Standard Deviation | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Sputum Inflammatory Markers - Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including granulocyte-macrophage colony-stimulating factor (GM-CSF) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Only 4 subjects were able to produce sputum at all time points. | Posted | Mean | Full Range | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Sputum Inflammatory Markers - Interleukin-1 (IL-1) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including interleukin-1 (IL-1) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Only 4 subjects were able to produce sputum at all time points. | Posted | Mean | Full Range | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Sputum Inflammatory Markers - Interleukin-10 (IL-10) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including interleukin-10 (IL-10) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Only 4 subjects were able to produce sputum at all time points. | Posted | Mean | Full Range | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Sputum Inflammatory Markers - Interleukin-17 (IL-17) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including interleukin-17 (IL-17) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Only 4 subjects were able to produce sputum at all time points. | Posted | Mean | Full Range | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Sputum Inflammatory Markers - Interleukin-6 (IL-6) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including interleukin-6 (IL-6) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Only 4 subjects were able to produce sputum at all time points. | Posted | Mean | Full Range | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Sputum Inflammatory Markers - Interleukin-8 (IL-8) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including interleukin-8 (IL-8) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Only 4 subjects were able to produce sputum at all time points. | Posted | Mean | Full Range | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Sputum Inflammatory Markers - Macrophage Inflammatory Protein-3 Alpha (MIP-3a) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including macrophage inflammatory protein-3 alpha (MIP-3a) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Only 4 subjects were able to produce sputum at all time points. | Posted | Mean | Full Range | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| Secondary | Sputum Inflammatory Markers - Tumor Necrosis Factor Alpha (TNF-a) Measurements at Baseline, Day 7, and Day 28 | Sputum inflammatory markers including tumor necrosis factor alpha (TNF-a) were collected at baseline and at the visits 7 days and 28 days post human mesenchymal stem cell (hMSC) infusion. Mean values with range are shown. | Only 4 subjects were able to produce sputum at all time points. | Posted | Mean | Full Range | pg/ml | Baseline, Day 7, Day 28 post human mesenchymal stem cell infusion |
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| 0 |
| 3 |
| 2 |
| 3 |
| 2 |
| 3 |
| EG001 | 3 x 10^6 Human Allogeneic Mesenchymal Stem Cells Per Kilogram | One time intravenouos infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram body weight (hMSCs/kg). A dose escalation using the "3+3" design was employed. The three doses were 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There was no placebo group. All study participants received stem cells. Mesenchymal Stem Cells (MSCs): A single dose, one time infusion (in the vein) of one of the following doses of hMSCs: 1 x 10^6, 3 x 10^6 or 5 x 10^6 hMSCs/kg body weight during Visit 2. A traditional 3+3 design was utilized. Allogeneic MSCs were derived from bone marrow aspirates from a healthy donor whose serum tested negative for cytomegalovirus (CMV) antibodies. The healthy donor underwent tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the MSCs were 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. | 0 | 3 | 2 | 3 | 2 | 3 |
| EG002 | 5 x 10^6 Human Allogeneic Mesenchymal Stem Cells Per Kilogram | One time intravenouos infusion of up to 5 x 10^6 allogeneic human mesenchymal stem cells per kilogram body weight (hMSCs/kg). A dose escalation using the "3+3" design was employed. The three doses were 1 x 10^6, 3 x 10^6, and 5 x 10^6 hMSCs/kg. There was no placebo group. All study participants received stem cells. Mesenchymal Stem Cells (MSCs): A single dose, one time infusion (in the vein) of one of the following doses of hMSCs: 1 x 10^6, 3 x 10^6 or 5 x 10^6 hMSCs/kg body weight during Visit 2. A traditional 3+3 design was utilized. Allogeneic MSCs were derived from bone marrow aspirates from a healthy donor whose serum tested negative for cytomegalovirus (CMV) antibodies. The healthy donor underwent tests for infectious disease and screening for 41 common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. In addition, the MSCs were 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. | 0 | 8 | 2 | 8 | 8 | 8 |
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| Constipation | Gastrointestinal disorders | Systematic Assessment | Constipation requiring admission to the hopsital. |
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| Right Common Iliac Thrombus | Vascular disorders | Systematic Assessment | Right common iliac thrombus requiring hospital admission. |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Constipation | Eye disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Hemorrhoids | Gastrointestinal disorders | Systematic Assessment |
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| Change in Appetite | Gastrointestinal disorders | Systematic Assessment |
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| Bleeding Hemorrhoids | Gastrointestinal disorders | Systematic Assessment |
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| Slow Weight Gain | Gastrointestinal disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Non-cardiac Chest Pain | General disorders | Systematic Assessment |
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| Risk of Pathogen Exposure | General disorders | Systematic Assessment |
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| Febrile Viral Illness | Immune system disorders | Systematic Assessment |
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| Upper Respiratory Infection | Infections and infestations | Systematic Assessment |
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| Influenza | Infections and infestations | Systematic Assessment |
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| Urinary Tract Infection | Infections and infestations | Systematic Assessment |
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| Fracture | Injury, poisoning and procedural complications | Systematic Assessment |
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| Weight Loss | Gastrointestinal disorders | Systematic Assessment |
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| Hypomagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Bilateral Lower Extremity Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Body Aches | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Generalized Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Right Heel Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Headahche | Nervous system disorders | Systematic Assessment |
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| Aphasia | Nervous system disorders | Systematic Assessment |
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| Dizziness | Nervous system disorders | Systematic Assessment |
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| Lethargy | Nervous system disorders | Systematic Assessment |
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| Memory Impairment | Nervous system disorders | Systematic Assessment |
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| Syncope | Nervous system disorders | Systematic Assessment |
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| Anxiety | Psychiatric disorders | Systematic Assessment |
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| Confusion | Psychiatric disorders | Systematic Assessment |
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| Depression | Psychiatric disorders | Systematic Assessment |
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| Suicidal Ideation | Psychiatric disorders | Systematic Assessment |
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| Cystoscopy | Renal and urinary disorders | Systematic Assessment |
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| Hematuria | Renal and urinary disorders | Systematic Assessment |
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| Increased Creatinine | Renal and urinary disorders | Systematic Assessment |
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| Ureter Stricture | Renal and urinary disorders | Systematic Assessment |
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| Urinary Hesitancy | Renal and urinary disorders | Systematic Assessment |
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| Urinary Retention | Renal and urinary disorders | Systematic Assessment |
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| Urology Procedure | Renal and urinary disorders | Systematic Assessment |
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| Breast Swelling | Reproductive system and breast disorders | Systematic Assessment |
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| Increased Sputum Production | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Cystic Fibrosis Pulmonary Exacerbation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Decreased FEV1 | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Sore Throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Hemoptysis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Sinus Congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Shortness of Breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Cold Sore | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Left Buttock Condyloma | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Left Shoulder Cyst Removal | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Mild Pruritus Ani | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Mild Non-Tender, Non-Fluctuant Erythema Around IV Insertion Site | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Hematoma | Vascular disorders | Systematic Assessment |
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| Right leg edema | Vascular disorders | Systematic Assessment |
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| PICC Line Insertion | Surgical and medical procedures | Systematic Assessment |
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| CT Scan of Right Lower Extermity | Surgical and medical procedures | Systematic Assessment |
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| Left Popliteal Venogram and Lysis Catheter Placement | Surgical and medical procedures | Systematic Assessment |
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| Lysis Catheter Removal | Surgical and medical procedures | Systematic Assessment |
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| PICC Line | Surgical and medical procedures | Systematic Assessment |
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| PICC Line Right Upper Extremity | Surgical and medical procedures | Systematic Assessment |
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Not provided
Not provided
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
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| FEV1 4 hours post infusion |
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| FEV1 24 hours post infusion |
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| FEV1 7 days post infusion |
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| FEV1 14 days post infusion |
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| FEV1 28 days post infusion |
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| FEV1 3 months post infusion |
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| FEV1 6 months post infusion |
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