Safety of biweekly α1-antitrypsin treatment in the RAPID programme

Abstract

Administration of 120 mg·kg−1 α1-antitrypsin on a biweekly basis was safe and well tolerated http://ow.ly/CVbz30lUBum

Trial registration: ClinicalTrials.gov NCT00261833 NCT00670007.

Conflict of interest statement

Conflict of interest: T. Greulich reports personal fees from AstraZeneca and GSK (lecture fees), Boehringer-Ingelheim, Chiesi, CSL Behring and Novartis (lecture fees, advisory board and travel support), and Mundipharma (lecture fees and advisory board); and grants and personal fees from Grifols (AATD-Labor, lecture fees and travel support), all outside the submitted work. Conflict of interest: J. Chlumsky reports honoraria for lectures organised by CSL Behring, and for lectures organised by Boehringer Ingelheim, outside the submitted work. Conflict of interest: M. Wencker reports support from conresp as a consultant to CSL Behring, during the conduct of the study. Conflict of interest: O. Vit reports support from CSL Behring, as employer and sponsor of the study. Conflict of interest: M. Fries reports support from CSL Behring, as employer and sponsor of the study. Conflict of interest: T. Chung reports support from CSL Behring, as employer and sponsor of the study. Conflict of interest: A. Shebl reports support from CSL Behring, as employer and sponsor of the study. Conflict of interest: C. Vogelmeier reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols and Novartis; personal fees from CSL Behring, Chiesi, Menarini, Mundipharma, Teva and Cipla; and grants from Bayer-Schering, MSD and Pfizer, all outside the submitted work. Conflict of interest: K.R. Chapman reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, Grifols, Sanofi, Genentech, Kamada, Roche and Novartis; grants from Baxter, GlaxoSmithKline, Amgen, Shire and Octapharma; personal fees from Merck; and the CIHR-GSK Research Chair in Respiratory Health Care Delivery, UHN, all during the conduct of the study. Conflict of interest: N.G. McElvaney reports research grants for carrying out the original RAPID and RAPID OLE studies from CSL Behring, during the conduct of the study; and personal fees from CSL Behring (advisory board), outside the submitted work.

Figures

FIGURE 1

Patient flow, demographics and disease characteristics at baseline for patients who received at least one biweekly 120 mg·kg−1 α1-antitrypsin (α1-AT) infusion or matching placebo during RAPID (Randomised Trial of Augmentation Therapy in Alpha-1 Proteinase Inhibitor Deficiency)-Randomised Controlled Trial (RCT) or RAPID-Open Label Extension (OLE), and safety of α1-AT infusion sequences compared to placebo in RAPID-RCT occurring 7 days prior to and within 7 days after the administration of 120 mg·kg−1. Data are presented as mean±sd or n. Where only two data points were available, the individual data are shown in brackets. EAER: exposure-adjusted event rates (events per subject-years), parameter that takes into account all treatment-emergent adverse events (TEAEs) during the trial except the periods with unknown infusion volumes, which were omitted (64 out of 29 076 infusions); IAER: infusion-adjusted event rate (events per n infusion sequences), intra-individual comparison of TEAEs that includes individuals that have received 120 mg·kg−1 biweekly infusions. An infusion sequence consisted of a 60 mg·kg−1 weekly infusion or matching placebo followed by one or more infusions of biweekly 120 mg·kg−1 or matching placebo. In this analysis the number of TEAEs occurring within the 7-day period prior to a double-dose infusion while exposed to 60 mg·kg−1 or matching placebo was compared with those occurring in the 7-day period following the biweekly 120 mg·kg−1 infusion or matching placebo; Pi*Z: α1-AT deficiency; FEV1: forced expiratory volume in 1 s; PI: proteinase inhibitor; NA: not applicable. #: data obtained at baseline of RCT. ¶: biweekly infusion sequences with α1-AT during RCT n=321 and during OLE n=563, total n=884. +: biweekly infusion sequences with placebo during RCT n=332. §: drug exposure for α1-AT group 60 mg weekly in RAPID-RCT was 158.20 subject-years; number of infusions (I) 8098; RAPID-OLE early treatment group 135.02 subject-years, I=6948; RAPID-OLE late treatment group 113.27 subject-years, I=5814. ƒ: drug exposure for α1-AT group 120 mg weekly in RAPID-RCT was 14.09 subject-years, I=333; RAPID-OLE early treatment group 12.50 subject-years, I=297; RAPID-OLE late treatment group 12.69 subject-years, I=303. ##: drug exposure for placebo group 120 mg weekly in RAPID-RCT was 134.92 subject-years, I=6845. ¶¶: drug exposure for placebo group 120 mg weekly in RAPID-RCT was 15.55 subject-years, I=374.