Efficacy and Safety of Alpha1-Proteinase Inhibitor (Human), Modified Process (Alpha-1 MP) in Subjects With Pulmonary Emphysema Due to Alpha1 Antitrypsin Deficiency (AATD) (SPARTA)
Primary Purpose
Pulmonary Emphysema in Alpha-1 PI Deficiency
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Alpha-1 MP
0.9% Sodium Chloride for Injection, USP
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Emphysema in Alpha-1 PI Deficiency focused on measuring Pulmonary Emphysema, Alpha-1 Antitrypsin Deficiency, AATD, Alpha-1 PI Deficiency, Alpha-1 Proteinase Inhibitor
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.
Sites / Locations
- St. Joseph's Hospital and Medical Center
- University of Miami Miller School of Medicine
- PMG Research
- Oregon Health & Science University
- Medical University of South Carolina
- University of Texas Health Center at Tyler
- St Vincent's Hospital Sydney
- The Prince Charles Hospital
- Royal Adelaide Hospital
- St Vincent's Hospital Melbourne
- Institute for Respiratory Health Inc
- Faculdade de Medicina do ABC
- UNIFESP - Universidade Federal de São Paulo
- Instituto do Coração - Incor- HCFMUSP
- Health Sciences Centre
- Queen Elizabeth II Health Sciences Centre
- Inspiration Research Limited
- Århus Universitetshospital
- Gentofte Hospital
- North Estonia Medical Centre Foundation
- Tartu University Hospital
- Turku University Central Hospital, Department of Pulmonary Diseases
- Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
- New Zealand Respiratory and Sleep institute
- Christchurch Hospital NZ
- Waikato Hospital
- SPZOZ Szpital Uniwersytecki w Krakowie
- Instytut Gruzlicy i Chorob Pluc w Warszawie
- SBEI HPE Altai State Medical University of MoH and SD
- SAIH of Yaroslavl region "Clinical Hospital of Emergency Medical Care n.a. N. V. Solovyev
- Sahlgrenska Sjukhuset
- CTC - Clinical Trial Consultants AB
- Skånes Universitetssjukhus, Malmö
- Karolinska Universitetssjukhuset, Solna
- CTC Clinical Trial Consultants AB
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Alpha-1 MP 60 mg/kg
Alpha-1 MP 120 mg/kg
Placebo
Arm Description
Alpha-1 MP 60 mg/kg administered weekly by IV infusion for 156 weeks
Alpha-1 MP 120 mg/kg administered weekly by IV infusion for 156 weeks
0.9% Sodium Chloride for Injection, USP, administered weekly by IV infusion for 156 weeks
Outcomes
Primary Outcome Measures
Change from Baseline in Whole lung PD15 (15th percentile point)
Whole lung PD15 measured by CT scan
Secondary Outcome Measures
Adverse Events (AEs)
Monitoring of AEs
Serious Adverse Events (SAEs)
Monitoring of SAEs
Discontinuations from the study due to AEs
Monitoring of discontinuations due to AEs
Severe COPD Exacerbations
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
PD15 of the basal lung region measure by CT scan
Change from baseline in carbon monoxide diffusing capacity (DLco)
DLco performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines
Changes from baseline in forced expiratory volume in 1 second (FEV1)
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
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
Heath-related quality of life assessment tool
Full Information
NCT ID
NCT01983241
First Posted
October 28, 2013
Last Updated
July 24, 2023
Sponsor
Grifols Therapeutics LLC
1. Study Identification
Unique Protocol Identification Number
NCT01983241
Brief Title
Efficacy and Safety of Alpha1-Proteinase Inhibitor (Human), Modified Process (Alpha-1 MP) in Subjects With Pulmonary Emphysema Due to Alpha1 Antitrypsin Deficiency (AATD)
Acronym
SPARTA
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
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 2013 (Actual)
Primary Completion Date
July 2026 (Anticipated)
Study Completion Date
July 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Grifols Therapeutics LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Emphysema in Alpha-1 PI Deficiency
Keywords
Pulmonary Emphysema, Alpha-1 Antitrypsin Deficiency, AATD, Alpha-1 PI Deficiency, Alpha-1 Proteinase Inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
341 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Alpha-1 MP 60 mg/kg
Arm Type
Experimental
Arm Description
Alpha-1 MP 60 mg/kg administered weekly by IV infusion for 156 weeks
Arm Title
Alpha-1 MP 120 mg/kg
Arm Type
Experimental
Arm Description
Alpha-1 MP 120 mg/kg administered weekly by IV infusion for 156 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
0.9% Sodium Chloride for Injection, USP, administered weekly by IV infusion for 156 weeks
Intervention Type
Biological
Intervention Name(s)
Alpha-1 MP
Other Intervention Name(s)
Prolastin-C
Intervention Type
Other
Intervention Name(s)
0.9% Sodium Chloride for Injection, USP
Other Intervention Name(s)
Saline
Primary Outcome Measure Information:
Title
Change from Baseline in Whole lung PD15 (15th percentile point)
Description
Whole lung PD15 measured by CT scan
Time Frame
Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156
Secondary Outcome Measure Information:
Title
Adverse Events (AEs)
Description
Monitoring of AEs
Time Frame
Week -3 through Week 160
Title
Serious Adverse Events (SAEs)
Description
Monitoring of SAEs
Time Frame
Week -3 through Week 160
Title
Discontinuations from the study due to AEs
Description
Monitoring of discontinuations due to AEs
Time Frame
Week -3 through Week 160
Title
Severe COPD Exacerbations
Description
Severe COPD exacerbations as defined by American Thoracic Society/European Respiratory Society (ATS/ERS) criteria (i.e., COPD exacerbations requiring hospitalization)
Time Frame
Week -3 through Week 160
Title
Change from Baseline in PD15 of the basal lung region
Description
PD15 of the basal lung region measure by CT scan
Time Frame
Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156
Title
Change from baseline in carbon monoxide diffusing capacity (DLco)
Description
DLco performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines
Time Frame
Weeks 26, 52, 78, 104, 130 and 156
Title
Changes from baseline in forced expiratory volume in 1 second (FEV1)
Description
FEV1 performed according to ATS/ERS guidelines
Time Frame
Weeks 26, 52, 78, 104, 130 and 156
Title
Change from baseline in Saint George's Respiratory Questionnaire: Minimum value = 0, maximum value = 100, higher scores indicate worse condition
Description
Health-related quality of life assessment tool
Time Frame
Weeks 26, 52, 78, 104, 130 and 156
Title
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
Description
Heath-related quality of life assessment tool
Time Frame
Weeks 26, 52, 78, 104, 130 and 156
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
St. Joseph's Hospital and Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
University of Miami Miller School of Medicine
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
PMG Research
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
University of Texas Health Center at Tyler
City
Tyler
State/Province
Texas
ZIP/Postal Code
75708
Country
United States
Facility Name
St Vincent's Hospital Sydney
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
The Prince Charles Hospital
City
Chermside
State/Province
Queensland
ZIP/Postal Code
4032
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
St Vincent's Hospital Melbourne
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
Institute for Respiratory Health Inc
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Faculdade de Medicina do ABC
City
Santo André
State/Province
Sao Paulo
ZIP/Postal Code
09060-650
Country
Brazil
Facility Name
UNIFESP - Universidade Federal de São Paulo
City
São Paulo
State/Province
Sao Paulo
ZIP/Postal Code
04023-061
Country
Brazil
Facility Name
Instituto do Coração - Incor- HCFMUSP
City
São Paulo
ZIP/Postal Code
05403-000
Country
Brazil
Facility Name
Health Sciences Centre
City
St. John's
State/Province
Newfoundland and Labrador
ZIP/Postal Code
A1B 3V6
Country
Canada
Facility Name
Queen Elizabeth II Health Sciences Centre
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H3A8
Country
Canada
Facility Name
Inspiration Research Limited
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T3A11
Country
Canada
Facility Name
Århus Universitetshospital
City
Arhus C
ZIP/Postal Code
8000
Country
Denmark
Facility Name
Gentofte Hospital
City
Hellerup
ZIP/Postal Code
2900
Country
Denmark
Facility Name
North Estonia Medical Centre Foundation
City
Tallinn
ZIP/Postal Code
13419
Country
Estonia
Facility Name
Tartu University Hospital
City
Tartu
ZIP/Postal Code
51014
Country
Estonia
Facility Name
Turku University Central Hospital, Department of Pulmonary Diseases
City
Turku
ZIP/Postal Code
20520
Country
Finland
Facility Name
Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
City
Bron
State/Province
Rhone
ZIP/Postal Code
69500
Country
France
Facility Name
New Zealand Respiratory and Sleep institute
City
Auckland
ZIP/Postal Code
1051
Country
New Zealand
Facility Name
Christchurch Hospital NZ
City
Christchurch
ZIP/Postal Code
8013
Country
New Zealand
Facility Name
Waikato Hospital
City
Hamilton
ZIP/Postal Code
3240
Country
New Zealand
Facility Name
SPZOZ Szpital Uniwersytecki w Krakowie
City
Krakow
ZIP/Postal Code
31-066
Country
Poland
Facility Name
Instytut Gruzlicy i Chorob Pluc w Warszawie
City
Warszawa
ZIP/Postal Code
01-138
Country
Poland
Facility Name
SBEI HPE Altai State Medical University of MoH and SD
City
Barnaul
ZIP/Postal Code
656038
Country
Russian Federation
Facility Name
SAIH of Yaroslavl region "Clinical Hospital of Emergency Medical Care n.a. N. V. Solovyev
City
Yaroslavl
ZIP/Postal Code
150003
Country
Russian Federation
Facility Name
Sahlgrenska Sjukhuset
City
Göteborg
ZIP/Postal Code
41345
Country
Sweden
Facility Name
CTC - Clinical Trial Consultants AB
City
Linköping
ZIP/Postal Code
587 58
Country
Sweden
Facility Name
Skånes Universitetssjukhus, Malmö
City
Malmö
ZIP/Postal Code
20502
Country
Sweden
Facility Name
Karolinska Universitetssjukhuset, Solna
City
Stockholm
ZIP/Postal Code
11361
Country
Sweden
Facility Name
CTC Clinical Trial Consultants AB
City
Uppsala
ZIP/Postal Code
752 37
Country
Sweden
12. IPD Sharing Statement
Citations:
PubMed Identifier
25727857
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.
Results Reference
derived
Learn more about this trial
Efficacy and Safety of Alpha1-Proteinase Inhibitor (Human), Modified Process (Alpha-1 MP) in Subjects With Pulmonary Emphysema Due to Alpha1 Antitrypsin Deficiency (AATD)
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