Efficacy and Safety of Alpha1-Proteinase Inhibitor (Human), Modified Process (Alpha-1 MP) in Subjects With Pulmonary Emphysema Due to Alpha1 Antitrypsin Deficiency (AATD)
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
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.
Primary outcome measure(s)
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
Trial sites (52)
Facility
City
Region
Status
Grifols Investigative Site
Phoenix
Arizona
Grifols Investigative Site
Gainesville
Florida
Grifols Investigative Site
Leesburg
Florida
Grifols Investigative Site
Miami
Florida
Grifols Investigative Site
St Louis
Missouri
Grifols Investigative Site
Wilmington
North Carolina
Grifols Investigative Site
Portland
Oregon
Grifols Investigative Site
Hershey
Pennsylvania
Grifols Investigative Site
Charleston
South Carolina
Grifols Investigative Site
Tyler
Texas
Grifols Investigative Site
Vicente López
Buenos Aires
Grifols Investigative Site
Córdoba
Córdoba Province
Grifols Investigative Site
Sydney
New South Wales
Grifols Investigative Site
Chermside
Queensland
Grifols Investigative Site
Adelaide
South Australia
Grifols Investigative Site
Fitzroy
Victoria
Grifols Investigative Site
Nedlands
Western Australia
Grifols Investigative Site
Santo André
São Paulo
Grifols Investigative Site
São Paulo
São Paulo
Grifols Investigative Site
São Paulo
São Paulo
Grifols Investigative Site
St. John's
Newfoundland and Labrador
Grifols Investigative Site
Halifax
Nova Scotia
Grifols Investigative Site
Toronto
Ontario
Grifols Investigative Site
Arhus C
Denmark
Grifols Investigative Site
Hellerup
Denmark
Grifols Investigative Site
Tallinn
Estonia
Grifols Investigative Site
Tartu
Estonia
Grifols Investigative Site
Turku
Finland
Grifols Investigative Site
Pessac
Gironde
Grifols Investigative Site
Bron
Rhone
Grifols Investigative Site
Heidelberg
Baden-Wurttemberg
Grifols Investigative Site
Marburg
Hesse
Grifols Investigative Site
Essen
North Rhine-Westphalia
Grifols Investigative Site
Homburg Saar
Germany
Grifols Investigative Site
Chisinau
Moldova
Grifols Investigative Site
Auckland
New Zealand
Grifols Investigative Site
Christchurch
New Zealand
Grifols Investigative Site
Hamilton
New Zealand
Grifols Investigative Site
Krakow
Poland
Grifols Investigative Site
Warsaw
Poland
+ 12 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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