Safety and efficacy results of simulated post-exposure prophylaxis with human immune globulin (HRIG; KEDRAB) co-administered with active vaccine in healthy subjects: a comparative phase 2/3 trial

3区 · 医学

Article

作者: Matson, Mark A. ; Nguyen, Huy-Binh ; Zamfirova, Vladislava ; Stein, Michal ; Bergman, Garrett E. ; Schenker, Eran

We conducted a clinical trial to assess the safety and putative efficacy of an additional human rabies immune globulin (HRIG; KEDRAB) versus an older product (Comparator, HyperRAB S/D® [Grifols]) and determine whether HRIG interferes with development of endogenous antibodies versus Comparator, when each is given with an active rabies vaccine. This was a prospective, double-blind, single-period, non-inferiority study in which subjects were randomized (1:1) to a single dose (20 IU/kg) of HRIG or Comparator on day 0 and rabies vaccine (RabAvert® [GlaxoSmithKline]; 1 mL of ≥2.5 IU/mL) on days 0, 3, 7, 14, and 28. Anti-rabies antibodies were measured by rapid fluorescent focus inhibition test on day 14, and subjects were followed until day 185. Rabies virus neutralizing antibody (RVNA) titers ≥0.5 IU/mL were considered seroconversion putatively indicative of protection. The non-inferiority criterion was the lower limit of the 90% confidence interval (CI) >-10%, for the between-group difference in the proportion of subjects achieving RVNA ≥0.5 IU/mL. On day 14, 98.3% of 59 subjects in the HRIG group and 100% of 59 in the Comparator group had RVNA ≥0.5 IU/mL (difference between proportions - 1.8%; 90% CI, - 8.2, 3.1; non-inferiority criterion met). One subject in the HRIG group did not meet the seroconversion criteria for anti-rabies antibody, and one subject in the Comparator group showed an anamnestic response, with much higher than expected anti-rabies antibody levels at both baseline and on day 14. Thus, HRIG allows for prophylactic anti-rabies antibody titers and is non-inferior to Comparator, when administered with rabies vaccine.

2013-12-01·American Journal of Hematology1区 · 医学

Hyperimmune globulins and same‐day thrombotic adverse events as recorded in a large healthcare database during 2008–2011

1区 · 医学

Article

作者: Divan, Hozefa A. ; Liang, Yideng ; Menis, Mikhail ; Izurieta, Hector S. ; Anderson, Steven A. ; Ovanesov, Mikhail V. ; Selvam, Nandini ; Ball, Robert ; Golding, Basil ; Scott, Dorothy ; Forshee, Richard ; Sridhar, Gayathri

Thrombotic events (TEs) are rare serious complications following administration of hyperimmune globulin (HIG) products. Our retrospective claims‐based study assessed occurrence of same‐day TEs following administration of HIGs during 2008–2011 and examined potential risk factors using HealthCore's Integrated Research Database (HIRDSM) and laboratory testing of products' procoagulant Factor XIa activity by U.S. Food and Drug Administration. Multivariable regression was used to estimate same‐day TE risk for different products. Of 101,956 individuals exposed to 23 different HIG product groups, 86 (0.84 per 1,000 persons) had a TE diagnosis code (DC) recorded on the same day as HIG administration. Unadjusted same‐day TE DC rates (per 1,000 persons) ranged from 0.4 to 148.9 for different products. GamaSTAN S/D IG >10 cc had statistically significantly higher same‐day TE DC risk compared to Tetanus IG (OR = 57.57; 95% CI = 19.72–168.10). Increased TE risk was also observed with older age (≥45 years), prior thrombotic events, and hypercoagulable state(s). Laboratory investigation identified elevated Factor XIa activity for GamaSTAN S/D, HepaGam B, HyperHep B S/D, WinRho SDF, HyperRHO S/D full dose, and HyperTET S/D. Our study, for the first time, identified increase in the same‐day TE DC risk with GamaSTAN S/D IG >10 cc and suggests potentially elevated TE risk with other HIGs. Am. J. Hematol. 88:1035–1040, 2013. © 2013 Wiley Periodicals, Inc.

Physical Review Letters1区 · 物理与天体物理

Constraining the Phase ofBs−B¯sMixing

1区 · 物理与天体物理

Article

作者: Grossman, Yuval ; Raz, Guy ; Nir, Yosef

New physics contributions to Bs-Bs mixing can be parametrized by the size (rs2) and the phase (2thetas) of the total mixing amplitude relative to the standard model amplitude. The phase has so far been unconstrained. We first use the D0 measurement of the semileptonic CP asymmetry ASL to obtain the first constraint on the semileptonic CP asymmetry in Bs decays, ASLs=-0.008+/-0.011. Then we combine recent measurements by the CDF and D0 Collaborations--the mass difference (DeltaMs), the width difference (DeltaGammas), and ASL;s--to constrain 2thetas. The errors on DeltaGammas and ASL;s should still be reduced to have a sensitive probe of the phase, yet the central values are such that the regions around 2thetas approximately 3pi/2 and, in particular, 2thetas approximately pi/2, are disfavored.

100 项与重组乙型肝炎免疫球蛋白相关的药物交易

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