Pulmonary Emphysema in Alpha-1 PI Deficiency
Conditions
Keywords
Pulmonary Emphysema, Alpha-1 Antitrypsin Deficiency, AATD, Alpha-1 PI Deficiency, Alpha-1 Proteinase Inhibitor
Brief summary
This is a multi-center, randomized, placebo-controlled, double blind clinical study to assess the efficacy and safety of two separate dose regimens of Alpha-1 MP versus placebo for 156 weeks (i.e., 3 years) using computed tomography (CT) of the lungs as the main measure of efficacy. The two Alpha-1 MP doses to be tested are 60 mg/kg and 120 mg/kg administered weekly by IV infusion for 156 weeks. The study consists of an optional pre-screening phase, Screening Phase, a 156-week Treatment Phase, and an End of Study Visit at Week 160.
Interventions
BIOLOGICALAlpha-1 MP
OTHER0.9% Sodium Chloride for Injection, USP
Sponsors
Grifols Therapeutics LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Have a documented total alpha1-PI serum level \< 11 µM. * Have a diagnosis of congenital AATD with an allelic combination of ZZ, SZ, Z(null), (null)(null), S(null), or "at-risk" alleles. * At the Screening (Week -3) Visit, have a post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥ 30% and \< 80% of predicted and FEV1/forced vital capacity (FVC) \< 70% (Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] stage II or III). * Have a carbon monoxide diffusing capacity (DLCO) ≤ 60% of predicted (corrected for HgB) within the past 2 years OR evidence of pulmonary emphysema on CT scan within the past 2 years per the Investigator's judgment. * Have clinical evidence of pulmonary emphysema per the Investigator's judgment.
Exclusion criteria
* Has received alpha1-PI augmentation therapy for more than 1 month within the six months prior to the Screening Visit. * Has received alpha1-PI augmentation therapy within one month of the Screening Visit. * Has had a chronic obstructive pulmonary disease (COPD) exacerbation within the 5 weeks prior to the Screening Visit or during the Screening Phase. * Unable to physically (e.g., unable to fit inside the CT scanner) or mentally (e.g., claustrophobic) undergo a CT scan. * History of lung or liver transplant. * Any lung surgery during the past 2 years (excluding lung biopsy). * On the waiting list for lung surgery, including lung transplant. * Smoking during the past 12 months or a positive urine cotinine test at screening that is due to smoking. Maybe on Nicotine replacement, including vapor cigarettes. * History of anaphylaxis or severe systemic response to any plasma-derived alpha1-PI preparation or other blood product(s). * 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 Visit (inhaled steroids are not considered systemic steroids) or during the Screening Phase. * Use of systemic or aerosolized antibiotics for a COPD exacerbation within the 5 weeks prior to the Screening Visit or during the Screening Phase. * Known selective or severe Immunoglobulin A (IgA) deficiency.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Whole lung PD15 (15th percentile point) | Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156 | Whole lung PD15 measured by CT scan |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs) | Week -3 through Week 160 | Monitoring of AEs |
| Serious Adverse Events (SAEs) | Week -3 through Week 160 | Monitoring of SAEs |
| Discontinuations from the study due to AEs | Week -3 through Week 160 | Monitoring of discontinuations due to AEs |
| Severe COPD Exacerbations | Week -3 through Week 160 | Severe COPD exacerbations as defined by American Thoracic Society/European Respiratory Society (ATS/ERS) criteria (i.e., COPD exacerbations requiring hospitalization) |
| Change from Baseline in PD15 of the basal lung region | Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156 | PD15 of the basal lung region measure by CT scan |
| Change from baseline in carbon monoxide diffusing capacity (DLco) | Weeks 26, 52, 78, 104, 130 and 156 | DLco performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines |
| Changes from baseline in forced expiratory volume in 1 second (FEV1) | Weeks 26, 52, 78, 104, 130 and 156 | FEV1 performed according to ATS/ERS guidelines |
| Change from baseline in Saint George's Respiratory Questionnaire: Minimum value = 0, maximum value = 100, higher scores indicate worse condition | Weeks 26, 52, 78, 104, 130 and 156 | Health-related quality of life assessment tool |
| Change from baseline in the EuroQoL (Quality of Life)- 5 Dimension- 5 Level (EQ-5D-5L): Minimum value (for each one of the 5 levels) = 1, maximum value (for each one of the 5 levels) = 5, higher scores indicate worse condition | Weeks 26, 52, 78, 104, 130 and 156 | Heath-related quality of life assessment tool |
Countries
Argentina, Australia, Brazil, Canada, Denmark, Estonia, Finland, France, Germany, Moldova, New Zealand, Poland, Romania, Russia, Spain, Sweden, United States
Outcome results
None listed