SPARTA clinical trial design: Exploring the efficacy and safety of two dose regimens of alpha₁-proteinase inhibitor augmentation therapy in alpha₁-antitrypsin deficiency - 27/02/15

Doi : 10.1016/j.rmed.2015.01.022

Susan Sorrells ^a,^⁎ , Sandra Camprubi ^b, Rhonda Griffin ^a, Junliang Chen ^a, Jaume Ayguasanosa ^b
^a Grifols Inc., 79 TW Alexander Drive, Bldg 4201, P.O. Box 110526, Research Triangle Park, NC, USA
^b Instituto Grifols S.A., Parc Empresarial Can Joan, Av. De la Generalitat, 152–158, 08174 Sant Cugat del Vallés, Barcelona, Spain

^∗Corresponding author. Grifols Inc. P.O. Box 110526, 4201 Research Commons, 79 T. W. Alexander Drive, Research Triangle Park, NC 27709, USA. Tel.: +1 919 316 6582, +1 919 641 1828 (mobile); fax: +1 919 287 2939.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Friday 27 February 2015

Summary

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.

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Keywords : Alpha₁-antitrypsin deficiency, Alpha₁-proteinase inhibitor, Prolastin-C, Chronic obstructive pulmonary disease, SPARTA, CT densitometry