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.

Abstract

Background: Alpha1-antitrypsin deficiency (AATD) is an underdiagnosed genetic disorder that results in early-onset emphysema due to low serum levels of alpha1-proteinase inhibitor (alpha1-PI), leading to increased activity of tissue-damaging neutrophil elastase. Clinical outcomes of AATD may be improved by administering alpha1-PI augmentation therapy. Here, we describe the design of the ongoing Study of ProlAstin-c Randomized Therapy with Alpha-1 augmentation (SPARTA), a phase 3 trial designed to evaluate progression of lung tissue loss in patients with severe AATD receiving human alpha1-PI (Prolastin(®)-C) versus placebo, using whole-lung computed tomography (CT) densitometry.

Study design: SPARTA is a randomized, placebo-controlled trial assessing the efficacy and safety of two separate doses of Prolastin-C (60 and 120 mg/kg) administered weekly over 3 years in patients aged 18-70 years with a diagnosis of AATD and clinical evidence of pulmonary emphysema. The primary measure of efficacy (change from baseline whole-lung 15th percentile lung density [PD15]) will be determined by CT lung densitometry measured at total lung capacity. Secondary efficacy variables will be the evaluation of severe chronic obstructive pulmonary disease exacerbations, as defined by American Thoracic Society/European Respiratory Society criteria, and PD15 of the basal lung region using CT densitometry. Adverse events will be collected and documented.

Conclusions: The SPARTA trial is designed to evaluate the long-term (3-year) efficacy of 2 separate doses of Prolastin-C for the treatment of emphysema in patients with AATD. Protocol number: GTi1201.

Clinical trials identifier: NCT01983241.

Keywords: Alpha(1)-antitrypsin deficiency; Alpha(1)-proteinase inhibitor; CT densitometry; Chronic obstructive pulmonary disease; Prolastin-C; SPARTA.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon / methods
  • Adult
  • Aged
  • Biological Availability
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Lung / pathology*
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Pulmonary Emphysema* / diagnosis
  • Pulmonary Emphysema* / drug therapy
  • Pulmonary Emphysema* / etiology
  • Research Design
  • Respiratory Function Tests
  • Serine Proteinase Inhibitors / administration & dosage
  • Serine Proteinase Inhibitors / adverse effects
  • Serine Proteinase Inhibitors / pharmacokinetics
  • Tomography, X-Ray Computed / methods
  • Treatment Outcome
  • alpha 1-Antitrypsin Deficiency / complications
  • alpha 1-Antitrypsin Deficiency / diagnosis
  • alpha 1-Antitrypsin Deficiency / drug therapy*
  • alpha 1-Antitrypsin Deficiency / physiopathology
  • alpha 1-Antitrypsin* / administration & dosage
  • alpha 1-Antitrypsin* / adverse effects
  • alpha 1-Antitrypsin* / pharmacokinetics

Substances

  • Serine Proteinase Inhibitors
  • alpha 1-Antitrypsin

Associated data

  • ClinicalTrials.gov/NCT01983241