A Phase 1, First-in-Human, Clinical Trial to Evaluate the Safety of Small Mobile Stem Cells (SMS) Delivered Into the Lung as a Potential Organ Regeneration Therapy in Chronic Obstructive Pulmonary Disease (SORT-COPD Study
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 3
- 主要终点
- Adverse events.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 39 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 39 to 69 years (inclusive).
- •Female participants:
- •A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
- •Is a woman of nonchildbearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method from screening until 30 days after the last dose of study intervention.
- •A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) at Screening and on Day 1, prior to administration of study intervention.
- •If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- •The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
- •Male participants:
- •Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 30 days after the last dose of study intervention:
- •Refrain from donating fresh unwashed semen. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR must agree to use contraception/barrier (male condom).
- •Has a diagnosis of mild or moderate COPD-C (cigarette smoking COPD) or COPD-P (biomass and pollution exposure COPD) according to the 2023 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Criteria.
- •Lung impairment will be determined with post-bronchodilator FEV1 spirometry.
- •Has previously received treatment for COPD-C or COPD-P.
- •Has stable COPD disease state, defined as no exacerbations in the 12 weeks prior to screening, no hospitalizations in the 12 weeks prior to screening, and no changes in COPD medication in the 28 days prior to screening.
- •Agrees to comply with study specific procedures and visits, including non-smoking during the treatment and follow-up periods of the study.
- •Willing and able to provide written informed consent.
排除标准
- •Previous or current diagnosis of COPD-G, COPD-D, COPD-I, COPD-A or COPD-U; asthma, congestive heart failure, bronchiectasis, tuberculosis, obliterative bronchiolitis or diffuse panbronchiolitis.
- •Previous or current history of respiratory failure other than due to COPD (e.g. restrictive lung disease, sarcoidosis, tuberculosis, idiopathic pulmonary fibrosis, bronchiectasis, CMV pneumonitis, cystic fibrosis, asbestosis, silicosis or farmer's lung disease), or detection of any of these conditions through screening CT scanning.
- •History of COVID associated pneumonia with hypoxemic respiratory failure in the 12 weeks prior to screening.
- •Current use, or use within 21 days of screening, of systemic corticosteroids. Participants on inhaled corticosteroids or combined inhaled therapies can be included, however must schedule inhaled therapies 12 hours prior to dosing IP and 12-hours post dosing IP.
- •Any history of chronic liver disease, or abnormal liver function at screening, defined as:
- •Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) more than 2.5 times the upper limit of normal (ULN) Total bilirubin more than two times the ULN Participants with documented Gilbert's syndrome are permitted to enter the study.
- •History of chronic renal insufficiency, defined as and eGFR < 90 mL/min/1.73 m
- •Participants without a history of chronic renal insufficiency, who at screening have an eGFR detected between 60-89 mL/min/1.73 m2, should have their eGFR repeated as per standard clinical procedure.
- •Uncontrolled hypertension, or current hypertension controlled on more than two medications.
- •History, within the last two years, of coronary artery disease, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, severe peripheral arterial disease, cerebrovascular disease (including history of transient ischemic attack or cerebrovascular accident), or any such history that, in the opinion of the investigator, will impact participation in the study.
- •Type 1 or Type 2 diabetes mellitus with glycosylated hemoglobin (HbA1c > 7.5%) at screening.
- •No active malignancy in the last three years, including any potential neoplasm detected via high-resolution CT scan (nodule > 5 mm) detected as part of the screening process.
- •People with a history of basal cell or squamous cell carcinoma of the skin are eligible.
- •History of HIV or other immunosuppressed conditions, Hepatitis B or Hepatitis C, or use of immunosuppressive medications within 14 days prior to screening, and for 3 weeks after the last dose of study intervention is administered.
- •Active infection requiring systemic antibiotic treatment within 12 weeks prior to screening.
- •Body mass index (BMI) > 60 kg/m
- •Active smoking of tobacco, cannabis or vaping in the 28 days prior to screening as indicated by results of cotinine urine testing, performed at screening. Use of nicotine containing products such as nicotine patches, oral nicotine products or nicotine chewing gum is permitted, noting that cotinine results will be positive. Positive results will be documented by the investigator as "attributed to permitted nicotine products".
- •History of alcohol or other substance abuse, with sobriety less than one year, or that in the opinion of the investigator, will impact participation in the study.
- •Pregnant or breastfeeding.
- •Any severe medication allergy, including an allergy to bovine products.
- •Any other medical condition, psychiatric condition or illness, that according to the Principal Investigator might render the subject unlikely to tolerate the inhalation of SORT-COPD (SMS cells), or to complete the study.
- •Current participation in any other clinical trial or participation in the last six weeks or subject received an experimental therapy (drug or biologic) for any indication within 12 months prior to enrolment.
- •Unable or unwilling to comply with study specific schedules or procedures.
研究组 & 干预措施
Participants in the cohort 1 (low dose) will receive 1.2 billion cells/ml.
Dose escalating Cohort 1.
干预措施: Stem cells (Biological)
Participants in the cohort 2 (medium dose) will receive 2.4 billion cells/ml.
Dose escalating Cohort 2.
干预措施: Stem cells (Biological)
Participants in the cohort 3 (high dose) will receive 4.8 billion cells/m
Dose Escalating Cohort 3.
干预措施: Stem cells (Biological)
结局指标
主要结局
Adverse events.
时间窗: Day 1, 2, 3, 4, 5, 8, 9, 21, 28, Month 3 and Month 6.
Treatment emergent adverse events and serious adverse events.
Dose limiting toxicity.
时间窗: Day 1, 2, 3, 4, 5, 8, 9, 21, 28, Month 3 and Month 6.
Any treatment emergent adverse event that ii treatment related and classified as severe or the event is classified as a serious adverse event.
Safety laboratory testing
时间窗: Screening, Day 2, 3, 5, 9, 21 and 28.
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.
次要结局
- Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)(Screening and Day 28.)
- Pulse oximetry(Screening, Day 1, 2, 3, 4, 5, 8, 9, 21 and 28.)
- 6-minute walk-test(Screening, Day 1, 5, 9, 21 and 28.)
- Exhaled Nitirc Oxide Test(Screening, Day 1, 2, 3, 4, 5, 8, 9, 21 and 28.)
- St George Respiratory Questionnaire for COPD(Screening, Day 1, Day 28, Month 3 and Month 6.)
- Spirometry(Screening, Day 1, 2, 3, 4, 5, 8, 9, 21 and 28.)
- Oscillometry(Screening, Day 1 and 28.)
- Plethysmograhy(Screening and Day 28.)