This study is a phase 1, first-in-human, open-label, non-randomized, dose escalation safety study of 18 participants, between 39 and 69 years of age, with mild to moderate chronic obstructive pulmonary disease, treated with SORT-COPD (SMS cells). The primary objective of this study is to determine the safety of SORT-COPD (SMS cells) at three doses in people with chronic obstructive pulmonary disease.
The suspension of stem cells will be put in a medical nebulizer machine, commonly used to deliver medicines into the lungs through inhalation. This means that the participants will breathe in the mist containing the SMS cells, produced by the nebulizer machine. This is a Phase I First-in-Human study, which indicates that this treatment is being studied for the first time in humans. 18 participants are expected to be enrolled into this study. Participants will be divided into three groups of six volunteers, with the first group receiving the lowest dose of the study treatment, the second group receiving a higher dose, and the third group receiving the highest dose. Between each of the three groups, there will be a pause to permit detection of any short-term adverse effects of the treatment at a specific dose. Participants will be treated with the study drug, SORT COPD (Small Mobile Stem Cells), delivered via a medical nebuliser on the 1st, 4th, and the 8th days of the study in-clinic. The nebuliser treatment involves inhaling mist from a mouthpiece attached to a standard medical nebuliser machine and takes about 10 to 15 minutes to complete. The volume to be nebulised is 3 millilitres (less than one teaspoon). Participants in the cohort 1 (low dose) will receive 1.2 billion cells/ml. Participants in the cohort 2 (medium dose) will receive 2.4 billion cells/ml. Participants in the cohort 3 (high dose) will receive 4.8 billion cells/ml. The study treatment (SMS) cells will be given in three different concentrations with the lowest dose given to the 1st group of 6 participants, with the dose doubled for each group. The members of each group will receive the same dose at each treatment visit. Participants will actively be in the study for up to 5 or 6 weeks, including the initial screening and testing period before the treatment is applied, during treatment, and about 4 weeks after the first treatment. Also, about 3 to 6 months after the study, participants will be contacted via telephone to answer some questions about their state of health, which will be the end of the study. Individual participant duration will be up to a maximum of 15 months.
Study Type
INTERVENTIONAL
The suspension of stem cells will be put in a medical nebulizer machine, commonly used to deliver medicines into the lungs through inhalation. This means that the participants will breathe in the mist containing the SMS cells, produced by the nebulizer machine. This is a Phase I First-in-Human study, which indicates that this treatment is being studied for the first time in humans.
Doherty Clinical Trials Limited
Melbourne, Victoria, Australia
RECRUITINGAdverse events.
Treatment emergent adverse events and serious adverse events.
Time frame: Day 1, 2, 3, 4, 5, 8, 9, 21, 28, Month 3 and Month 6.
Dose limiting toxicity.
Any treatment emergent adverse event that ii treatment related and classified as severe or the event is classified as a serious adverse event.
Time frame: Day 1, 2, 3, 4, 5, 8, 9, 21, 28, Month 3 and Month 6.
Safety laboratory testing
All laboratory parameters will be summarized using descriptive statistics for each cohort and overall, for all time points assessed, including change from baseline for all post-dose assessments. Selected laboratory test results will be graded in accordance with the NCI CTCAE criteria.
Time frame: Screening, Day 2, 3, 5, 9, 21 and 28.
Spirometry
To be performed according to the American Thoracic Society/European Respiratory Society Standards. Forced Expiratory Volume in 1 second (FEV1) measured in liters (L).
Time frame: Screening, Day 1, 2, 3, 4, 5, 8, 9, 21 and 28.
Spirometry
To be performed according to the American Thoracic Society/European Respiratory Society Standards. Forced Vital Capacity (FVC) measured in liters (L).
Time frame: Screening, Day 1, 2, 3, 4, 5, 8, 9, 21 and 28.
Oscillometry
Resistance measured in cm H2O s/L .
Time frame: Screening, Day 1 and 28.
Oscillometry
Resistance change measured in cm H2O s/L..
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Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Time frame: Screening, Day 1 and 28.
Oscillometry
Reactance of respiratory system measured in cm H2O s/L.
Time frame: Screening, Day 1 and 28.
Plethysmograhy
Functional Residual Capacity (FRC) measured in liters (L).
Time frame: Screening and Day 28.
Plethysmograhy
Total Lung Capacity (TLC) measured in liters (L).
Time frame: Screening and Day 28.
Plethysmograhy
Ratio of Residual Volume measured as a percentage (%).
Time frame: Screening and Day 28.
Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)
DLCO measured in milliliters per min per millimeter of Mercury (mL/min/mmHg).
Time frame: Screening and Day 28.
Pulse oximetry
Measuring oxygen saturation in the participants blood (SpO2)
Time frame: Screening, Day 1, 2, 3, 4, 5, 8, 9, 21 and 28.
6-minute walk-test
Assessment of exercise tolerance , distance walked in 6-minutes measured in meters (m).
Time frame: Screening, Day 1, 5, 9, 21 and 28.
Exhaled Nitirc Oxide Test
The fractional exhaled nitric oxide (FENO) test measures the amount of nitric oxide that is exhaled from a breath. It is a marker of lung inflammation, and is useful for differentiating asthma from COPD and other conditions presenting with similar symptoms \[26\]. FENO values of \< 25 parts per billion (ppb) are considered normal, 25-50 ppb as intermediate and \> 50 ppb as high.
Time frame: Screening, Day 1, 2, 3, 4, 5, 8, 9, 21 and 28.
St George Respiratory Questionnaire for COPD
Measurement of quality of life validated for participants with COPD. Each subscale and the total score range from 0 (no impact) to 100 (worst possible impact).
Time frame: Screening, Day 1, Day 28, Month 3 and Month 6.