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)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pulmonary Emphysema in Alpha-1 PI Deficiency
• Intervention / Treatment: Biological: Alpha-1 MP; Other: 0.9% Sodium Chloride for Injection, USP

• Study Type: Interventional
• Enrollment (Actual): 345
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: David Taylor; Email: david.taylor@grifols.com
• Study Contact Backup: Name: Gordon McAlester; Email: gordon.mcalester@grifols.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • The Prince Charles Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Institute for Respiratory Health Inc
• Brazil
  • São Paulo, Brazil, 05403-000
    • Instituto do Coração - Incor- HCFMUSP
  • Sao Paulo
    • Santo André, Sao Paulo, Brazil, 09060-650
      • Faculdade de Medicina do ABC
    • São Paulo, Sao Paulo, Brazil, 04023-061
      • UNIFESP - Universidade Federal de São Paulo
• Canada
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Health Sciences Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H3A8
      • Queen Elizabeth II Health Sciences Centre
  • Ontario
    • Toronto, Ontario, Canada, M5T3A11
      • Inspiration Research Limited
• Denmark
  • Arhus C, Denmark, 8000
    • Århus Universitetshospital
  • Hellerup, Denmark, 2900
    • Gentofte Hospital
• Estonia
  • Tallinn, Estonia, 13419
    • North Estonia Medical Centre Foundation
  • Tartu, Estonia, 51014
    • Tartu University Hospital
• Finland
  • Turku, Finland, 20520
    • Turku University Central Hospital, Department of Pulmonary Diseases
• France
  • Rhone
    • Bron, Rhone, France, 69500
      • Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
• New Zealand
  • Auckland, New Zealand, 1051
    • New Zealand Respiratory and Sleep institute
  • Christchurch, New Zealand, 8013
    • Christchurch Hospital NZ
  • Hamilton, New Zealand, 3240
    • Waikato Hospital
• Poland
  • Krakow, Poland, 31-066
    • SPZOZ Szpital Uniwersytecki w Krakowie
  • Warszawa, Poland, 01-138
    • Instytut Gruzlicy i Chorob Pluc w Warszawie
• Russian Federation
  • Barnaul, Russian Federation, 656038
    • SBEI HPE Altai State Medical University of MoH and SD
  • Yaroslavl, Russian Federation, 150003
    • SAIH of Yaroslavl region "Clinical Hospital of Emergency Medical Care n.a. N. V. Solovyev
• Sweden
  • Göteborg, Sweden, 41345
    • Sahlgrenska Sjukhuset
  • Linköping, Sweden, 587 58
    • CTC - Clinical Trial Consultants AB
  • Malmö, Sweden, 20502
    • Skånes Universitetssjukhus, Malmo
  • Stockholm, Sweden, 11361
    • Karolinska Universitetssjukhuset, Solna
  • Uppsala, Sweden, 752 37
    • CTC Clinical Trial Consultants AB
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Accellacare
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Tyler, Texas, United States, 75708
      • University of Texas Health Center at Tyler

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alpha-1 MP 60 mg/kg; Alpha-1 MP 60 mg/kg administered weekly by IV infusion for 156 weeks	Biological: Alpha-1 MP; Other Names: Prolastin-C
Experimental: Alpha-1 MP 120 mg/kg; Alpha-1 MP 120 mg/kg administered weekly by IV infusion for 156 weeks	Biological: Alpha-1 MP; Other Names: Prolastin-C
Placebo Comparator: Placebo; 0.9% Sodium Chloride for Injection, USP, administered weekly by IV infusion for 156 weeks	Other: 0.9% Sodium Chloride for Injection, USP; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Whole lung PD15 (15th percentile point)	Whole lung PD15 measured by CT scan	Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Monitoring of AEs	Week -3 through Week 160
Serious Adverse Events (SAEs)	Monitoring of SAEs	Week -3 through Week 160
Discontinuations from the study due to AEs	Monitoring of discontinuations due to AEs	Week -3 through Week 160
Severe COPD Exacerbations	Severe COPD exacerbations as defined by American Thoracic Society/European Respiratory Society (ATS/ERS) criteria (i.e., COPD exacerbations requiring hospitalization)	Week -3 through Week 160
Change from Baseline in PD15 of the basal lung region	PD15 of the basal lung region measure by CT scan	Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156
Change from baseline in carbon monoxide diffusing capacity (DLco)	DLco performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines	Weeks 26, 52, 78, 104, 130 and 156
Changes from baseline in forced expiratory volume in 1 second (FEV1)	FEV1 performed according to ATS/ERS guidelines	Weeks 26, 52, 78, 104, 130 and 156
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	Weeks 26, 52, 78, 104, 130 and 156
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	Weeks 26, 52, 78, 104, 130 and 156

Collaborators and Investigators

• Sponsor: Grifols Therapeutics LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2013
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: October 28, 2013
• First Submitted That Met QC Criteria: November 7, 2013
• First Posted (Estimated): November 13, 2013

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Alpha-1 Antitrypsin Deficiency; Pulmonary Emphysema; AATD; Alpha-1 PI Deficiency; Alpha-1 Proteinase Inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Liver Diseases; Genetic Diseases, Inborn; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Subcutaneous Emphysema; Chronic Disease; Pulmonary Emphysema; Emphysema; Alpha 1-Antitrypsin Deficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Alpha 1-Antitrypsin
• Other Study ID Numbers: GTi1201