Efficacy and Safety of Alpha1-Proteinase Inhibitor (Human), Modified Process (Alpha-1 MP) in Subjects With Pulmonary Emphysema Due to Alpha1 Antitrypsin Deficiency (AATD)
- Conditions
- Pulmonary Emphysema in Alpha-1 PI Deficiency
- Interventions
- Other: 0.9% Sodium Chloride for Injection, USPBiological: Alpha-1 MP
- Registration Number
- NCT01983241
- Lead Sponsor
- Grifols Therapeutics LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 345
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo 0.9% Sodium Chloride for Injection, USP 0.9% Sodium Chloride for Injection, USP, administered weekly by IV infusion for 156 weeks Alpha-1 MP 120 mg/kg Alpha-1 MP Alpha-1 MP 120 mg/kg administered weekly by IV infusion for 156 weeks Alpha-1 MP 60 mg/kg Alpha-1 MP Alpha-1 MP 60 mg/kg administered weekly by IV infusion for 156 weeks
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Discontinuations from the study due to AEs Week -3 through Week 160 Monitoring of discontinuations due to AEs
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
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
Adverse Events (AEs) Week -3 through Week 160 Monitoring of AEs
Serious Adverse Events (SAEs) Week -3 through Week 160 Monitoring of SAEs
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
Trial Locations
- Locations (52)
Institutul de Ftiziopneumologie "Chiril Draganiuc"
🇲🇩Chisinau, Moldova, Republic of
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Medical Research of Central Florida, LLC
🇺🇸Leesburg, Florida, United States
Accellacare
🇺🇸Wilmington, North Carolina, United States
Faculdade de Medicina do ABC
🇧🇷Santo André, Sao Paulo, Brazil
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Penn State Univ. Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Texas Health Center at Tyler
🇺🇸Tyler, Texas, United States
Hospital del Torax Dr. Antonio A. Cetrangolo
🇦🇷Vicente Lopez, Buenos Aires, Argentina
Centro Dr. Lazaro Langer
🇦🇷Cordoba, Argentina
St Vincent's Hospital Sydney
🇦🇺Sydney, New South Wales, Australia
The Prince Charles Hospital
🇦🇺Chermside, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Institute for Respiratory Health Inc
🇦🇺Nedlands, Western Australia, Australia
St Vincent's Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
UNIFESP - Universidade Federal de São Paulo
🇧🇷São Paulo, Sao Paulo, Brazil
Instituto do Coração - Incor- HCFMUSP
🇧🇷São Paulo, Brazil
Health Sciences Centre
🇨🇦St. John's, Newfoundland and Labrador, Canada
Queen Elizabeth II Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
Inspiration Research Limited
🇨🇦Toronto, Ontario, Canada
Århus Universitetshospital
🇩🇰Arhus C, Denmark
Gentofte Hospital
🇩🇰Hellerup, Denmark
North Estonia Medical Centre Foundation
🇪🇪Tallinn, Estonia
Tartu University Hospital
🇪🇪Tartu, Estonia
Turku University Central Hospital, Department of Pulmonary Diseases
🇫🇮Turku, Finland
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Baden Wuerttemberg, Germany
Universitaetsklinikum Giessen und Marburg GmbH
🇩🇪Marburg, Hessen, Germany
Groupe Hospitalier Sud - Hôpital Haut-Lévêque
🇫🇷Pessac, Gironde, France
Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
🇫🇷Bron, Rhone, France
Ruhrlandklinik
🇩🇪Essen, Nordrhein Westfalen, Germany
Univer des Saarlandes Innere
🇩🇪Homburg Saar, Germany
New Zealand Respiratory and Sleep institute
🇳🇿Auckland, New Zealand
Christchurch Hospital NZ
🇳🇿Christchurch, New Zealand
Waikato Hospital
🇳🇿Hamilton, New Zealand
SPZOZ Szpital Uniwersytecki w Krakowie
🇵🇱Krakow, Poland
Instytut Gruzlicy i Chorob Pluc w Warszawie
🇵🇱Warszawa, Poland
SAIH of Yaroslavl region "Clinical Hospital of Emergency Medical Care n.a. N. V. Solovyev
🇷🇺Yaroslavl, Russian Federation
Clinic Dr.G Curteanu Oradea
🇷🇴Oradea, Romania
Spitalul Clinic de Boli Infectioase si Pneumoftiziologie
🇷🇴Timisoara, Romania
SBEI HPE Altai State Medical University of MoH and SD
🇷🇺Barnaul, Russian Federation
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Asturias, Spain
Hospital de Cruces
🇪🇸Barakaldo, Vizcaya, Spain
FSI Scientific Research Institute of Pulmonology
🇷🇺Moscow, Russian Federation
Sahlgrenska Sjukhuset
🇸🇪Göteborg, Sweden
CTC - Clinical Trial Consultants AB
🇸🇪Linköping, Sweden
Skånes Universitetssjukhus, Malmö
🇸🇪Malmö, Sweden
Karolinska Universitetssjukhuset, Solna
🇸🇪Stockholm, Sweden
CTC Clinical Trial Consultants AB
🇸🇪Uppsala, Sweden