A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of PROCHYMAL™ (ex Vivo Cultured Adult Human Mesenchymal Stem Cells) Intravenous Infusion for the Treatment of Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Overview
- Phase
- Phase 2
- Intervention
- Prochymal™
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Sponsor
- Mesoblast, Inc.
- Enrollment
- 62
- Locations
- 6
- Primary Endpoint
- Number of Participants with Adverse Events (AEs)
- Status
- Completed
- Last Updated
- last month
Overview
Brief Summary
The objective of the present study is to establish the safety and efficacy of multiple administrations of Prochymal™(ex-vivo cultured human adult mesenchymal stem cells) in participants with moderate to severe chronic obstructive pulmonary disease (COPD).
Detailed Description
COPD is currently the fourth leading cause of death in the United States. It is clear that there is a significant unmet medical need for safe and effective therapies to treat moderate to severe COPD. This patient population has a high mortality rate and requires frequent hospitalizations due to disease-related exacerbations. Based on severity distribution estimates, approximately 70% of all current COPD patient have either moderate or severe COPD. COPD has no known cure, thus current therapeutic intervention is aimed at providing relief of symptoms. Oxygen therapy is the only treatment that has been shown to improve survival. Smoking cessation has been shown to slow the rate of forced expiratory volume in 1 second (FEV1) decline and COPD progression. In general patient are treated with bronchodilators and inhaled corticosteroids, but again, these measures do not provide any significant benefit regarding disease progression or prognosis. The characteristics and biologic activity of Prochymal™, along with a good safety profile in human trials to date, suggest that Prochymal™ may be a good candidate for addressing this unmet medical need.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participant must have a diagnosis of moderate or severe COPD.
- •Participant must have a post-bronchodilator FEV1/forced vital capacity (FVC) ratio \< 0.
- •Participant must have a post-bronchodilator FEV1 % predicted value ≥ 30% and \< 70%.
- •Participant must be between 40 and 80 years of age, of either sex, and of any race.
- •Participant must be a current or ex-smoker, with a cigarette smoking history of ≥ 10 years or \> 10 pack-years.
Exclusion Criteria
- •Participant has been 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).
- •Participant has been diagnosed with α1-antitrypsin deficiency.
- •Participant has a body mass greater than 150 kg (330 lb) or less than 40 kg (88 lb).
- •Participant has active infection.
- •Participant has had a significant exacerbation of COPD or has required mechanical ventilation within 4 weeks of screening.
- •The participant with clinically relevant uncontrolled medical condition not associated with COPD.
- •Participant has documented history of uncontrolled heart failure.
- •Participant has pulmonary hypertension due to left heart condition.
- •Participant has atrial fibrillation or significant congenital heart defect/disease.
- •Participant has initiated pulmonary rehabilitation within 3 months of screening.
Arms & Interventions
Prochymal™
Participants received Prochymal™ a total of 400×10\^6 cells, intravenous (IV) infusions on Days 0, 30, 60, and 90.
Intervention: Prochymal™
Placebo
Participants received placebo-matching IV infusions on Days 0, 30, 60 and 90.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants with Adverse Events (AEs)
Time Frame: Up to 2 Years
Secondary Outcomes
- Change from Baseline in Functional residual capacity (FRC) at Month 6(Baseline, Month 6)
- Change from Baseline in Total Lung Capacity (TLC) at Month 6(Baseline, Month 6)
- Change from Baseline in Pulmonary Function Test: Forced Expiratory Volume (FEV)1 at Year 1 and Year 2(Baseline, Year 1, Year 2)
- Change from Baseline in Pulmonary Function Test: Forced Expiratory Volume (FEV)1 %predicted at Year 1 and Year 2(Baseline, Year 1, Year 2)
- Change from Baseline in Borg Dyspnea Scale at Year 2(Baseline, Year 2)
- Change from Baseline in Diffusing capacity of the lung for carbon monoxide (DLCO) %predicted at Year 1 and Year 2(Baseline, Year 1, Year 2)
- Change from Baseline in Residual Volume (RV) at Month 6(Baseline, Month 6)
- Change from Baseline in Airway Resistance (RAW) at Month 6(Baseline, Month 6)
- Change from Baseline in 6-Minute Walk Test at Year 1 and Year 2(Baseline, Year 1, Year 2)
- Change from Baseline in Pulmonary Function Test: Forced Vital Capacity (FVC) at Year 1 and Year 2(Baseline, Year 1, Year 2)
- Change from Baseline in Pulmonary Function Test: Forced Vital Capacity (FVC) %predicted at Year 1 and Year 2(Baseline, Year 1, Year 2)
- Change from Baseline in Pulmonary Function Test: Forced Expiratory Volume to Forced Vital Capacity Ratio (FEV1/FVC) at Year 1 and Year 2(Baseline, Year 1, Year 2)
- Change from Baseline in Diffusing capacity of the lung for carbon monoxide (DLCO) at Year 1 and Year 2(Baseline, Year 1, Year 2)
- Change from Baseline in Alveolar Volume (VA) at Year 1 and Year 2(Baseline, Year 1, Year 2)
- Change from Baseline in Diffusing capacity of the lung for carbon monoxide to Alveolar Volume ratio (DLCO/VA)at Year 1 and Year 2(Baseline, Year 1, Year 2)
- Change from Baseline in Health-related quality of life: St George's Respiratory Questionnaire (SGRQ) at Year 1 and Year 2(Baseline, Year 1, Year 2)
- Change from Baseline in Physician Global Assessment Scale at Year 1 and Year 2(Baseline, Year 1, Year 2)
- Time to COPD Exacerbation(Up to 2 Years)
- Number of COPD Exacerbations(Up to 2 Years)
- Change from Baseline in Pulmonary Hypertension at Month 6(Baseline, Month 6)
- Change from Baseline in Systemic Inflammation at Year 1 and Year 2(Baseline, Year 1 and Year 2)