Treatment of Chronic Obstructive Pulmonary Disease by Infusion of Allogenic Mesenchymal Stem Cells

Official title

A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Safety And Efficacy Of Umc119-06-05 Intravenous Infusion For The Treatment Of Subjects With Moderate To Severe Chronic Obstructive Pulmonary Disease

Overview

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

• Other UMC119-06-05
  Human Umbilical Cord Derived-Mesenchymal Stem Cells

Primary outcome measures

• Incidence of treatment-emergent adverse events (TEAEs) [Time frame: From Baseline to Day 90]]
• Incidence of related TEAEs and serious adverse events (SAEs) [Time frame: through the study]
• Incidence of withdrawals due to adverse events (AEs) [Time frame: through the study]
• Change/shift from baseline in laboratory tests [Time frame: Baseline, 2 hours (h), Days 3, 7, 14, 28, 90]
• Change from baseline in vital signs [Time frame: Baseline, 0 minute, 2 h, Days 3, 7, 14, 28, 90]
• shift from baseline in ECG results [Time frame: Baseline, 2 h, Day 14]
• Shift from baseline in physical examination results [Time frame: Baseline, 2 h, Days 3, 7, and 14]

Secondary outcome measures (10)

• Mean change from baseline in forced vital capacity (FVC) [Time frame: Baseline, Days 28, 90, 180, 270, 360]
• Mean change from baseline in forced expiratory volume in one second (FEV1) [Time frame: Baseline, Days 28, 90, 180, 270, 360]
• Mean change from baseline in FEV1/FVC ratio [Time frame: Baseline, Days 28, 90, 180, 270, 360]
• Mean change from baseline in 6-minute walk test [Time frame: Baseline, Days 28, 90, 180, 270, 360]
• Mean change from baseline in St. George's Respiratory Questionnaire (SGRQ) score [Time frame: Baseline, Days 28, 90, 180, 270, 360]
• Shift from baseline in modified Medical Research Council (mMRC) dyspnea scale [Time frame: Baseline, Days 28, 90, 180, 270, 360]
• Incidence, frequency, and severity of COPD exacerbations [Time frame: through the study]
• Time to first COPD exacerbation [Time frame: through the study]
• 9. Mean change or shift from baseline in Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index [Time frame: baseline to Days 28, 90, 180, 270, 360]
• he number of times that rescue medication is used [Time frame: through the study]

Eligibility criteria

Inclusion criteria

• Between ≥40 and ≤80 years of age, of either sex and of any race.
• With diagnosis of COPD based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) standard.
• Has a post-bronchodilator FEV1/FVC ratio <0.70.
• Has a post-bronchodilator FEV1 predicted value ≥30% and <80%.
• With a score ≥2 in the mMRC dyspnea scale.
• With a score ≥10 in the COPD Assessment Test (CAT).
• With a body weight ≥40 to ≤90 kg.
• 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.
• Is a current or ex-smoker, with a cigarette smoking history of ≥10 years or >10 pack-years.
• 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

• 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.
• 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).
• 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.
• Has documented history of uncontrolled heart failure.
• Has pulmonary hypertension due to left heart condition.
• Has atrial fibrillation or significant congenital heart defect/disease.
• 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.
• Is hospitalized at screening.
• With current active infection including pulmonary infection, systemic infection, or severe local infections.
• Have the following conditions in laboratory tests at screening:

• >2 × upper limit of normal (ULN) for alanine aminotransferase (ALT) or aspartate aminotransferase (AST); or
• Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2; or
• White blood cells (WBC) <3.6 × 103/μL; or
• Platelet counts <150 × 103/μL; or
• Hemoglobin <10 g/dL; or
• Spot urine albumin-creatinine ratio (UACR) ≥30 mg/g; or
• Clinically significant hematuria or proteinuria deemed by the study investigator.
• With known stage ≥3 chronic kidney disease.
• 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.
• With known alpha-1 antitrypsin deficiency.
• With known allergy or hypersensitivity to any component of the investigational product (IP) formulation (normal saline and human serum albumin \[HSA\]).
• 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.

• 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.
• With known human immunodeficiency virus infection or immunocompromised.
• With a known history of alcohol abuse or drug abuse within 5 years prior to screening.
• Participating in another clinical study of new investigational therapies or have received an investigational therapy within 3 months prior to screening.
• Pregnant (or plan to become pregnant within 3 months after study treatment) or lactating.
• Has a life expectancy of <6 months.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Taiwan · 2 centers

• Taipei Medical University-Shuang Ho Hospital,Ministry of Health and Welfare — New Taipei City
• Chang Gung Memorial Hospital, Linkou — Taoyuan City

Identifiers

NCT: NCT06491043 · UMC119-06-05-COPD-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗