Clinical trial NCT01983241: Efficacy and Safety of Alpha1-Proteinase Inhibitor (Human), Modified Process (Alpha-1 MP) in Subjects With Pulmonary Emphysema Due to Alpha1 Antitrypsin Deficiency (AATD)
Official title: A Randomized, Double-Blind, Placebo Controlled Study to Assess the Efficacy and Safety of Two Dose Regimens (60 mg/kg and 120 mg/kg) of Weekly Intravenous Alpha1 Proteinase Inhibitor (Human) in Subjects With Pulmonary Emphysema Due to Alpha1 Antitrypsin Deficiency
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Pulmonary Emphysema in Alpha-1 PI Deficiency
Keywords: Pulmonary Emphysema
Alpha-1 Antitrypsin Deficiency
AATD
Alpha-1 PI Deficiency
Alpha-1 Proteinase Inhibitor
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2013-11-13
Enrollment: 345
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 outcomes:
measure: Change from Baseline in Whole lung PD15 (15th percentile point)
timeFrame: Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156
Secondary outcomes:
measure: Adverse Events (AEs)
timeFrame: Week -3 through Week 160
measure: Serious Adverse Events (SAEs)
timeFrame: Week -3 through Week 160
measure: Discontinuations from the study due to AEs
timeFrame: Week -3 through Week 160
measure: Severe COPD Exacerbations
timeFrame: Week -3 through Week 160
measure: Change from Baseline in PD15 of the basal lung region
timeFrame: Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156
measure: Change from baseline in carbon monoxide diffusing capacity (DLco)
timeFrame: Weeks 26, 52, 78, 104, 130 and 156
measure: Changes from baseline in forced expiratory volume in 1 second (FEV1)
timeFrame: Weeks 26, 52, 78, 104, 130 and 156
measure: Change from baseline in Saint George's Respiratory Questionnaire: Minimum value = 0, maximum value = 100, higher scores indicate worse condition
timeFrame: Weeks 26, 52, 78, 104, 130 and 156
measure: 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
timeFrame: Weeks 26, 52, 78, 104, 130 and 156
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Leesburg
country: United States
facility: Medical Research of Central Florida, LLC
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Wilmington
country: United States
facility: Accellacare
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Univ. Milton S. Hershey Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Tyler
country: United States
facility: University of Texas Health Center at Tyler
state: Texas
city: Vicente Lopez
country: Argentina
facility: Hospital del Torax Dr. Antonio A. Cetrangolo
state: Buenos Aires
city: Cordoba
country: Argentina
facility: Centro Dr. Lazaro Langer
city: Sydney
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Nedlands
country: Australia
facility: Institute for Respiratory Health Inc
state: Western Australia
city: Santo André
country: Brazil
facility: Faculdade de Medicina do ABC
state: Sao Paulo
city: São Paulo
country: Brazil
facility: UNIFESP - Universidade Federal de São Paulo
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Instituto do Coração - Incor- HCFMUSP
city: St. John's
country: Canada
facility: Health Sciences Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Toronto
country: Canada
facility: Inspiration Research Limited
state: Ontario
city: Arhus C
country: Denmark
facility: Århus Universitetshospital
city: Hellerup
country: Denmark
facility: Gentofte Hospital
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre Foundation
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Turku
country: Finland
facility: Turku University Central Hospital, Department of Pulmonary Diseases
city: Pessac
country: France
facility: Groupe Hospitalier Sud - Hôpital Haut-Lévêque
state: Gironde
city: Bron
country: France
facility: Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
state: Rhone
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
state: Baden Wuerttemberg
city: Marburg
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH
state: Hessen
city: Essen
country: Germany
facility: Ruhrlandklinik
state: Nordrhein Westfalen
city: Homburg Saar
country: Germany
facility: Univer des Saarlandes Innere
city: Chisinau
country: Moldova, Republic of
facility: Institutul de Ftiziopneumologie "Chiril Draganiuc"
city: Auckland
country: New Zealand
facility: New Zealand Respiratory and Sleep institute
city: Christchurch
country: New Zealand
facility: Christchurch Hospital NZ
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Krakow
country: Poland
facility: SPZOZ Szpital Uniwersytecki w Krakowie
city: Warszawa
country: Poland
facility: Instytut Gruzlicy i Chorob Pluc w Warszawie
city: Oradea
country: Romania
facility: Clinic Dr.G Curteanu Oradea
city: Timisoara
country: Romania
facility: Spitalul Clinic de Boli Infectioase si Pneumoftiziologie
city: Barnaul
country: Russian Federation
facility: SBEI HPE Altai State Medical University of MoH and SD
city: Moscow
country: Russian Federation
facility: FSI Scientific Research Institute of Pulmonology
city: Yaroslavl
country: Russian Federation
facility: SAIH of Yaroslavl region "Clinical Hospital of Emergency Medical Care n.a. N. V. Solovyev
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Barakaldo
country: Spain
facility: Hospital de Cruces
state: Vizcaya
city: Göteborg
country: Sweden
facility: Sahlgrenska Sjukhuset
city: Linköping
country: Sweden
facility: CTC - Clinical Trial Consultants AB
city: Malmö
country: Sweden
facility: Skånes Universitetssjukhus, Malmö
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset, Solna
city: Uppsala
country: Sweden
facility: CTC Clinical Trial Consultants AB
Study officials:
References:
citation: Sorrells S, Camprubi S, Griffin R, Chen J, Ayguasanosa J. SPARTA clinical trial design: exploring the efficacy and safety of two dose regimens of alpha1-proteinase inhibitor augmentation therapy in alpha1-antitrypsin deficiency. Respir Med. 2015 Apr;109(4):490-9. doi: 10.1016/j.rmed.2015.01.022. Epub 2015 Feb 13.