Dataset Information

A multicenter open-label treatment protocol (HGT-GCB-058) of velaglucerase alfa enzyme replacement therapy in patients with Gaucher disease type 1: safety and tolerability.

ABSTRACT: To evaluate the safety of velaglucerase alfa in patients with type 1 Gaucher disease who received velaglucerase alfa in the US treatment protocol HGT-GCB-058 (ClinicalTrials.gov identifier NCT00954460) during a global supply shortage of imiglucerase.This multicenter open-label treatment protocol enrolled patients who were either treatment naïve or had been receiving imiglucerase. Patients received intravenous velaglucerase alfa every other week at a dose of 60?U/kg (treatment naïve) or 15-60?U/kg (previously treated).A total of 211 (including six treatment-naïve) patients were enrolled. Among the 205 previously treated patients, 35 (17.1%) experienced an adverse event considered related to study drug. Among the six treatment-naïve patients, one had an adverse event considered related to study drug. Infusion-related adverse events occurred in 28 (13.3%) of the 211 patients and usually occurred during the first three infusions. De novo, nonneutralizing, anti-velaglucerase alfa antibodies developed during treatment in one (<1.0%) previously treated patient and none of the treatment-naïve patients.The currently observed safety profile was consistent with those previously reported for imiglucerase and velaglucerase alfa phase III clinical trials. These results support the safety of initiating treatment with velaglucerase alfa or transitioning patients from imiglucerase therapy to velaglucerase alfa therapy.

SUBMITTER: Pastores GM

PROVIDER: S-EPMC4018500 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A multicenter open-label treatment protocol (HGT-GCB-058) of velaglucerase alfa enzyme replacement therapy in patients with Gaucher disease type 1: safety and tolerability.

Pastores Gregory M GM Rosenbloom Barry B Weinreb Neal N Goker-Alpan Ozlem O Grabowski Gregory G Cohn Gabriel M GM Zahrieh David D

Genetics in medicine : official journal of the American College of Medical Genetics 20131121 5

<h4>Purpose</h4>To evaluate the safety of velaglucerase alfa in patients with type 1 Gaucher disease who received velaglucerase alfa in the US treatment protocol HGT-GCB-058 (ClinicalTrials.gov identifier NCT00954460) during a global supply shortage of imiglucerase.<h4>Methods</h4>This multicenter open-label treatment protocol enrolled patients who were either treatment naïve or had been receiving imiglucerase. Patients received intravenous velaglucerase alfa every other week at a dose of 60 U/k ...[more]

PMID: 24263462

Similar Datasets

Project description:Gaucher disease type 1, an inherited lysosomal storage disorder, is caused by mutations in GBA1 leading to defective glucocerebrosidase (GCase) function and consequent excess accumulation of glucosylceramide/glucosylsphingosine in visceral organs. Enzyme replacement therapy (ERT) with the biosimilars, imiglucerase (imig) or velaglucerase alfa (vela) improves/reverses the visceral disease. Comparative transcriptomic effects (microarray and mRNA-Seq) of no ERT and ERT (imig or vela) were done with liver, lung, and spleen from mice having Gba1 mutant alleles, termed D409V/null. Disease-related molecular effects, dynamic ranges, and sensitivities were compared between mRNA-Seq and microarrays and their respective analytic tools, i.e. Mixed Model ANOVA (microarray), and DESeq and edgeR (mRNA-Seq). While similar gene expression patterns were observed with both platforms, mRNA-Seq identified more differentially expressed genes (DEGs) (?3-fold) than the microarrays. Among the three analytic tools, DESeq identified the maximum number of DEGs for all tissues and treatments. DESeq and edgeR comparisons revealed differences in DEGs identified. In 9V/null liver, spleen and lung, post-therapy transcriptomes approximated WT, were partially reverted, and had little change, respectively, and were concordant with the corresponding histological and biochemical findings. DEG overlaps were only 8-20% between mRNA-Seq and microarray, but the biological pathways were similar. Cell growth and proliferation, cell cycle, heme metabolism, and mitochondrial dysfunction were most altered with the Gaucher disease process. Imig and vela differentially affected specific disease pathways. Differential molecular responses were observed in direct transcriptome comparisons from imig- and vela-treated tissues. These results provide cross-validation for the mRNA-Seq and microarray platforms, and show differences between the molecular effects of two highly structurally similar ERT biopharmaceuticals.

Dataset Information

A multicenter open-label treatment protocol (HGT-GCB-058) of velaglucerase alfa enzyme replacement therapy in patients with Gaucher disease type 1: safety and tolerability.

Publications

A multicenter open-label treatment protocol (HGT-GCB-058) of velaglucerase alfa enzyme replacement therapy in patients with Gaucher disease type 1: safety and tolerability.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets