SPARTA clinical trial design: exploring the efficacy and safety of two dose regimens of alpha1-proteinase inhibitor augmentation therapy in alpha1-antitrypsin deficiency.
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.


METHODS
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.


BACKGROUND
NCT01983241.
Grifols Inc., 79 TW Alexander Drive, Bldg 4201, P.O. Box 110526, Research Triangle Park, NC, USA. Electronic address: susan.sorrells@grifols.com.
Susan
S
Sorrells
Instituto Grifols S.A., Parc Empresarial Can Joan, Av. De la Generalitat, 152-158, 08174 Sant Cugat del Vallés, Barcelona, Spain.
Sandra
S
Camprubi
Grifols Inc., 79 TW Alexander Drive, Bldg 4201, P.O. Box 110526, Research Triangle Park, NC, USA.
Rhonda
R
Griffin
Grifols Inc., 79 TW Alexander Drive, Bldg 4201, P.O. Box 110526, Research Triangle Park, NC, USA.
Junliang
J
Chen
Instituto Grifols S.A., Parc Empresarial Can Joan, Av. De la Generalitat, 152-158, 08174 Sant Cugat del Vallés, Barcelona, Spain.
Jaume
J
Ayguasanosa
D015502:Absorptiometry, Photon / Q000379:methods; D000328:Adult; D000368:Aged; D001682:Biological Availability; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011656:Pulmonary Emphysema / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D012107:Research Design; D012129:Respiratory Function Tests; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology
D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin
Alpha(1)-antitrypsin deficiency; Alpha(1)-proteinase inhibitor; CT densitometry; Chronic obstructive pulmonary disease; Prolastin-C; SPARTA