Pulmonary Emphysema due to Alpha-1-Antitrypsin Deficiency MedDRA version: 20.0 Level: LLT Classification code 10014563 Term: Emphysema pulmonary System Organ Class: 100000004855
Conditions
Sponsors
Grifols Therapeutics LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have a documented total alpha1-PI serum level =65 years) yes F.1.3.1 Number of subjects for this age range 34
Exclusion criteria
Exclusion criteria: 1. Has received alpha1-PI augmentation therapy for more than 1 month within the six months prior to the Screening (Week -3) Visit. 2. Has received alpha1-PI augmentation therapy within one month of the Screening (Week -3) Visit. 3. Has had a COPD exacerbation within the 5 weeks prior to the Screening (Week -3) Visit or during the Screening Phase. Investigator discretion should be used to determine if a subject is appropriate for study participation if the subject has had a COPD exacerbation which occurred more than 5 weeks prior to the Screening (Week -3) Visit. 4. Unable to physically (e.g., unable to fit inside the CT scanner) or mentally (e.g., claustrophobic) undergo a CT scan. 5. History of lung or liver transplant. 6. Any lung surgery during the past 2 years (excluding lung biopsy). 7. On the waiting list for lung surgery, including lung transplant. 8. Smoking during the past 12 months or a positive urine cotinine test at screening that is due to smoking. 9. History of anaphylaxis or severe systemic response to any plasma-derived alpha1-PI preparation or other blood product(s). 10. Use of systemic steroids above a stable dose equivalent to 5 mg/day prednisone (i.e., 10 mg every 2 days) within the 5 weeks prior to the Screening (Week -3) Visit (inhaled steroids are not considered systemic steroids) or during the Screening Phase. It is recommended to maintain the same dose throughout the study. 11. Use of systemic or aerosolized antibiotics for a COPD exacerbation within the 5 weeks prior to the Screening (Week -3) Visit or during the Screening Phase. 12. Known selective or severe Immunoglobulin A (IgA) deficiency.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to demonstrate, using whole lung computed tomography (CT) densitometry (15th percentile point [PD15]), a slower progression of lung tissue loss in subjects with alpha1-antitrypsin deficiency (AATD) on Alpha-1 MP (alpha1-proteinase inhibitor [human], modified process) treatment (either 60 mg/kg/week or 120 mg/kg/week) as compared to placebo.;Secondary Objective: The secondary objectives of this study are to demonstrate the efficacy of each IV dose of Alpha-1 MP (either 60 mg/kg/week or 120 mg/kg/week) as compared to placebo in subjects with AATD by: - Reducing the incidence of severe COPD exacerbations as defined by an American Thoracic Society (ATS)/European Respiratory Society (ERS) Task Force criteria, and - Slowing the progression of lung tissue loss as measured by basal lung CT densitometry (PD15). The safety objective of this study is to evaluate the safety and tolerability of two separate IV dose regimens (60 mg/kg/week and 120 mg/kg/week) of Alpha-1 MP.;Primary end point(s): The primary objective of this study is to demonstrate, using whole lung computed tomography (CT) densitometry (15th percentile point [PD15]), a slower progression of lung tissue loss in subjects with alpha1-antitrypsin deficiency (AATD) on Alpha-1 MP (alpha1-proteinase inhibitor [human], modified process) treatment (either 60 mg/kg/week or 120 mg/kg/week) as compared to placebo.;Timepoint(s) of evaluation of this end point: weeks 52, 104,130 & 156 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary objectives of this study are to demonstrate the efficacy of each IV dose of Alpha-1 MP (either 60 mg/kg/week or 120 mg/kg/week) as compared to placebo in subjects with AATD by: - Reducing the incidence of severe COPD exacerbations as defined by an American Thoracic Society (ATS)/European Respiratory Society (ERS) Task Force criteria, and - Slowing the progression of lung tissue loss as measured by basal lung CT densitometry (PD15). The exploratory objectives for this study are to evaluate the effects of each IV dose of Alpha-1 MP (either 60 mg/kg/week or 120 mg/kg/week) as compared to placebo in subjects with AATD on: - The incidence and severity of COPD exacerbations as defined by ATS/ERS criteria, - Change from baseline in forced expiratory volume in 1 second (FEV1), and - Health-related quality of life as measured by the Saint George’s Respiratory Questionnaire (SGRQ). CT scan parameters other than basal and whole lung PD15 may also be evaluated. An additional exploratory objective is to compare the efficacy of 120 mg/kg/week Alpha-1 MP to 60 mg/kg/week Alpha-1 MP as evidenced by the change from baseline in whole lung PD15 using CT densitometry. The safety objective of this study is to evaluate the safety and tolerability of two separate IV dose regimens (60 mg/kg/week and 120 mg/kg/week) of Alpha-1 MP.;Timepoint(s) of evaluation of this end point: Throughout the study (please ref. ATS/ERS COPD Exacerbation Assessment row in Appendix1: study flow chart - page 64) | — |
Countries
Argentina, Australia, Brazil, Canada, Denmark, Estonia, Finland, France, Germany, Ireland, Moldova, Republic of, New Zealand, Poland, Romania, Russian Federation, Serbia, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactSusan Sorrells, Director, ClinDev
Grifols Therapeutics LLC
Outcome results
None listed