Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
This phase II study is a randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of UMC119-06-05 compared to placebo in treating subjects with moderate to severe COPD. Eligible subjects will receive a single-dose IV infusion of UMC119-06-05 or placebo.
Detailed description
Patients with chronic obstructive pulmonary disease (COPD) are characterized with airflow limitation and chronic inflammation, which is caused by cigarette smoking, noxious particles or gases. These inhaled irritants will induce inflammation, emphysema and fibrosis though chronic exposure. The current pharmacological treatment of COPD is symptomatic and is mainly based on bronchodilators and corticosteroids. Although current clinical treatment strategies can improve and stabilize COPD states and quality of life, none of them are able to modify the progressive decline in lung function, meaning it gradually gets worse over time. Therefore, development of new therapeutic modalities to improve the clinical outcomes and prognosis of COPD in adult patients is of urgent need. Among the more innovative, experimental therapies, mesenchymal stromal cells are proposed as a novel therapy with potential in treatment of COPD. This clinical trial is a phase II study. It is a randomized, placebo-controlled, double-blind study. Eligible subjects will be randomized to one of the three groups: placebo control, low-dose UMC119-06-05 treatment, or high-dose UMC119-06-05 treatment. Subjects will receive a single-dose IV infusion to evaluate the efficacy and long-term safety of UMC119-06-05 with moderate to severe COPD.
Interventions
OTHERUMC119-06-05
Human Umbilical Cord Derived-Mesenchymal Stem Cells
Sponsors
Meribank Biotech Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double-blind
Intervention model description
Eligible subjects will be randomized to one of the three groups: placebo control, low-dose allogeneic umbilical cord-derived mesenchymal stem cells UMC119-06-05 treatment, or high-dose UMC119-06-05 treatment.
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Between ≥40 and ≤80 years of age, of either sex and of any race. 2. With diagnosis of COPD based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) standard. 3. Has a post-bronchodilator FEV1/FVC ratio \<0.70. 4. Has a post-bronchodilator FEV1 predicted value ≥30% and \<80%. 5. With a score ≥2 in the mMRC dyspnea scale. 6. With a score ≥10 in the COPD Assessment Test (CAT). 7. With a body weight ≥40 to ≤90 kg. 8. The disease status of COPD has been stable as determined by the investigator, and the standard treatment for COPD was not adjusted within 3 months prior to screening. 9. Is a current or ex-smoker, with a cigarette smoking history of ≥10 years or \>10 pack-years. 10. Women of child-bearing potential should have a negative urine pregnancy test at screening, UNLESS they meet the following criteria: (1)Post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with the serum follicle stimulating hormone (FSH) level \>40 mIU/mL, OR; (2)6 weeks post-surgical bilateral oophorectomy with or without hysterectomy 11.Heterosexually active subjects must agree to use a double barrier method of birth control (or must have been surgically sterilized/post-menopausal) and not to donate sperms/eggs during the study. 12.Willing to provide written informed consent to participate in the study.
Exclusion criteria
1. Has evidence of active malignancy or prior history of active malignancy that has not been in complete remission for at least 5 years prior to screening. 2. Diagnosed with asthma or other clinically relevant lung disease other than COPD (e.g., restrictive lung diseases, sarcoidosis, tuberculosis, idiopathic pulmonary fibrosis, bronchiectasis, or lung cancer). 3. Has initiated pulmonary rehabilitation (e.g., exercise training) within 3 months prior to screening which, in the opinion of the Principal Investigator (PI), may affect the study's results. 4. Has documented history of uncontrolled heart failure. 5. Has pulmonary hypertension due to left heart condition. 6. Has atrial fibrillation or significant congenital heart defect/disease. 7. Has had a moderate or severe exacerbation of COPD (defined by GOLD standard) or has required mechanical ventilation (not including continuous positive airway pressure \[CPAP\]) within 30 days prior to screening. 8. Is hospitalized at screening. 9. With current active infection including pulmonary infection, systemic infection, or severe local infections. 10. Have the following conditions in laboratory tests at screening: 1. \>2 × upper limit of normal (ULN) for alanine aminotransferase (ALT) or aspartate aminotransferase (AST); or 2. Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m2; or 3. White blood cells (WBC) \<3.6 × 103/μL; or 4. Platelet counts \<150 × 103/μL; or 5. Hemoglobin \<10 g/dL; or 6. Spot urine albumin-creatinine ratio (UACR) ≥30 mg/g; or 7. Clinically significant hematuria or proteinuria deemed by the study investigator. 11. With known stage ≥3 chronic kidney disease. 12. Received systemic steroids or other immunosuppressants, immunomodulators, cytotoxic agents, chemotherapy, radiation therapy, or other cell therapies within 28 days or 5 half-lives, whichever is longer, prior to screening. 13. With known alpha-1 antitrypsin deficiency. 14. With known allergy or hypersensitivity to any component of the investigational product (IP) formulation (normal saline and human serum albumin \[HSA\]). 15. With a known history of drug-related anaphylaxis or other severe allergic reactions to drug. Note: Severe is defined as Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade 3 or greater. 16. Underwent major surgery (body organs that require anesthesia, such as tumor removal, open chest, heart surgery, abdominal surgery, intracranial surgery, or normal surgery for more than 3 hours, etc.) within 30 days prior to screening. 17. With known human immunodeficiency virus infection or immunocompromised. 18. With a known history of alcohol abuse or drug abuse within 5 years prior to screening. 19. Participating in another clinical study of new investigational therapies or have received an investigational therapy within 3 months prior to screening. 20. Pregnant (or plan to become pregnant within 3 months after study treatment) or lactating. 21. Has a life expectancy of \<6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change/shift from baseline in laboratory tests | Baseline, 2 hours (h), Days 3, 7, 14, 28, 90 | laboratory tests |
| Change from baseline in vital signs | Baseline, 0 minute, 2 h, Days 3, 7, 14, 28, 90 | measure vital signs |
| shift from baseline in ECG results | Baseline, 2 h, Day 14 | ECG check |
| Shift from baseline in physical examination results | Baseline, 2 h, Days 3, 7, and 14 | physical examination |
| Incidence of treatment-emergent adverse events (TEAEs) | From Baseline to Day 90] | Incidence of any treatment-emergent serious adverse events (SAE), defined as the composite of: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities. 2.Incidence of related TEAEs and serious adverse events (SAEs) 3.Incidence of withdrawals due to adverse events (AEs) 4.Change/shift from baseline in laboratory tests 5.Change from baseline in vital signs 6.Shift from baseline in ECG results 7.Shift from baseline in physical examination results |
| Incidence of related TEAEs and serious adverse events (SAEs) | through the study | Incidence of any treatment-emergent serious adverse events (SAE), defined as the composite of: death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities. 2.Incidence of related TEAEs and serious adverse events (SAEs) 3.Incidence of withdrawals due to adverse events (AEs) 4.Change/shift from baseline in laboratory tests 5.Change from baseline in vital signs 6.Shift from baseline in ECG results 7.Shift from baseline in physical examination results |
| Incidence of withdrawals due to adverse events (AEs) | through the study | AE incidence |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first COPD exacerbation | through the study | assess severity and exacerbation |
| Mean change from baseline in forced vital capacity (FVC) | Baseline, Days 28, 90, 180, 270, 360 | Respiratory functions (FVC) 2.Mean change from baseline in forced expiratory volume in one second (FEV1) 3.Mean change from baseline in FEV1/FVC ratio 4.Mean change from baseline in 6-minute walk test (6-MWT) 5.Mean change from baseline in St. George's Respiratory Questionnaire (SGRQ) score 6.Shift from baseline in modified Medical Research Council (mMRC) dyspnea scale 7.Incidence, frequency, and severity of COPD exacerbations 8.Time to first COPD exacerbation 9.Mean change or shift from baseline in Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index 10.The number of times that rescue medication is used |
| he number of times that rescue medication is used | through the study | times of rescue medication |
| 9. Mean change or shift from baseline in Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index | baseline to Days 28, 90, 180, 270, 360 | BODE index |
| Mean change from baseline in forced expiratory volume in one second (FEV1) | Baseline, Days 28, 90, 180, 270, 360 | Respiratory functions (FEV1) |
| Mean change from baseline in FEV1/FVC ratio | Baseline, Days 28, 90, 180, 270, 360 | Respiratory functions (FEV1/FVC) |
| Mean change from baseline in 6-minute walk test | Baseline, Days 28, 90, 180, 270, 360 | measure 6 minute walk distance |
| Mean change from baseline in St. George's Respiratory Questionnaire (SGRQ) score | Baseline, Days 28, 90, 180, 270, 360 | Georges Respiratory Questionnaire has scores range from 0 to 100, with higher scores indicating more limitations |
| Shift from baseline in modified Medical Research Council (mMRC) dyspnea scale | Baseline, Days 28, 90, 180, 270, 360 | mMRC dyspnea scale |
| Incidence, frequency, and severity of COPD exacerbations | through the study | assess severity of COPD |
Countries
Taiwan
Contacts
Primary ContactRay Chang, Ph.D.
Backup ContactJoseph Chen, Ph.D.
Outcome results
None listed