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)

• ClinicalTrials.gov Identifier: NCT01983241
• Recruitment Status: Active, not recruiting
• First Posted: November 13, 2013
• Last Update Posted: March 7, 2024
• Sponsor: Grifols Therapeutics LLC
• Information provided by (Responsible Party): Grifols Therapeutics LLC

Tracking Information

• First Submitted Date: October 28, 2013
• First Posted Date: November 13, 2013
• Last Update Posted Date: March 7, 2024
• Actual Study Start Date: November 2013
• Estimated Primary Completion Date: August 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 7, 2013)

Change from Baseline in Whole lung PD15 (15th percentile point) [ Time Frame: Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156 ]

Whole lung PD15 measured by CT scan

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 25, 2021)

• Adverse Events (AEs) [ Time Frame: Week -3 through Week 160 ]
  Monitoring of AEs
• Serious Adverse Events (SAEs) [ Time Frame: Week -3 through Week 160 ]
  Monitoring of SAEs
• Discontinuations from the study due to AEs [ Time Frame: Week -3 through Week 160 ]
  Monitoring of discontinuations due to AEs
• Severe COPD Exacerbations [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Weeks 26, 52, 78, 104, 130 and 156 ]
  DLco performed according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines
• Changes from baseline in forced expiratory volume in 1 second (FEV1) [ Time Frame: Weeks 26, 52, 78, 104, 130 and 156 ]
  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 [ Time Frame: 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 [ Time Frame: Weeks 26, 52, 78, 104, 130 and 156 ]
  Heath-related quality of life assessment tool

Original Secondary Outcome Measures (submitted: November 7, 2013)

• Adverse Events (AEs) [ Time Frame: Week -3 through Week 160 ]
• Serious Adverse Events (SAEs) [ Time Frame: Week -3 through Week 160 ]
• Discontinuations from the study due to AEs [ Time Frame: Week -3 through Week 160 ]
• Severe COPD Exacerbations [ Time Frame: 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 [ Time Frame: Week -3 (baseline measure), Week 52, Week 104, Week 130, Week 156 ]
  PD15 of the basal lung region measure by CT scan

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Pulmonary Emphysema in Alpha-1 PI Deficiency

Intervention

• Biological: Alpha-1 MP
  Other Name: Prolastin-C
• Other: 0.9% Sodium Chloride for Injection, USP
  Other Name: Saline

Study Arms

• Experimental: Alpha-1 MP 60 mg/kg
  Alpha-1 MP 60 mg/kg administered weekly by IV infusion for 156 weeks
  Intervention: Biological: Alpha-1 MP
• Experimental: Alpha-1 MP 120 mg/kg
  Alpha-1 MP 120 mg/kg administered weekly by IV infusion for 156 weeks
  Intervention: Biological: Alpha-1 MP
• Placebo Comparator: Placebo
  0.9% Sodium Chloride for Injection, USP, administered weekly by IV infusion for 156 weeks
  Intervention: Other: 0.9% Sodium Chloride for Injection, USP

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 3, 2023): 345
• Original Estimated Enrollment (submitted: November 7, 2013): 339
• Estimated Study Completion Date: January 2027
• Estimated Primary Completion Date: August 2026 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Brazil, Canada, Denmark, Estonia, Finland, France, New Zealand, Poland, Russian Federation, Sweden, United States
• Removed Location Countries: Argentina, Germany, Romania, Spain

Administrative Information

• NCT Number: NCT01983241
• Other Study ID Numbers: GTi1201
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Grifols Therapeutics LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Grifols Therapeutics LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Grifols Therapeutics LLC
• Verification Date: March 2024