Drug Information for ELAPRASE™ (idursulfase) Solution for intravenous infusionInitial U.S. Approval: 2006 (Shire US Manufacturing Inc.): 14. CLINICAL STUDIES

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  • The safety and efficacy of ELAPRASE were evaluated in a randomized, double-blind, placebo-controlled clinical study of 96 patients with Hunter syndrome. The study included patients with a documented deficiency in iduronate-2-sulfatase enzyme activity who had a percent predicted forced vital capacity (%-predicted FVC) less than 80%. The patients' ages ranged from 5 to 31 years. Patients who were unable to perform the appropriate pulmonary function testing, or those who could not follow protocol instructions were excluded from the study. Patients received ELAPRASE 0.5 mg/kg every week (n=32), ELAPRASE 0.5 mg/kg every other week (n=32), or placebo (n=32). The study duration was 53 weeks.

    The primary efficacy outcome assessment was a two-component composite score based on the sum of the ranks of the change from baseline to Week 53 in distance walked during a six-minute walk test (6-MWT) and the ranks of the change in %-predicted FVC. This two-component composite primary endpoint differed statistically significantly between the three groups, and the difference was greatest between the placebo group and the weekly treatment group (weekly ELAPRASE vs. placebo, p=0.0049).

    Examination of the individual components of the composite score showed that, in the adjusted analysis, the weekly ELAPRASE-treated group experienced a 35 meter greater mean increase in the distance walked in six minutes compared to placebo. The changes in %-predicted FVC were not statistically significant (Table 3).

    Table 3 Clinical Study Results
    ELAPRASE Weekly n=32One patient in the placebo group and one patient in the ELAPRASE group died before Week 53; imputation was by last observation carried forward in the intent-to-treat analysisPlacebo n=32ELAPRASE Weekly – Placebo
    BaselineWeek 53ChangeChange, calculated as Week 53 minus BaselineBaselineWeek 53ChangeDifference in Change
    Results from the 6-Minute Walk Test (Meters)
    Mean ± SD392 ± 108436 ± 13844 ± 70393 ± 106400 ± 1067 ± 5437 ± 16Observed mean ± SE 35 ± 14ANCOVA model based mean ± SE, adjusted for baseline disease severity, region, and age. (p=0.01)
    Median39742931403412-4
    Percentiles (25th, 75th)316, 488365, 5360, 94341, 469361, 460-30, 31
    Results from the Forced Vital Capacity Test (% of Predicted)
    Mean ± SD55.3 ± 15.958.7 ± 19.33.4 ± 10.055.6 ± 12.356.3 ± 15.70.8 ± 9.62.7 ± 2.5 4.3 ± 2.3 (p=0.07)
    Median54.959.22.157.454.6-2.5
    Percentiles (25th, 75th)43.6, 69.344.4, 70.7-0.8, 9.546.9, 64.443.8, 67.5-5.4, 5.0

    Measures of bioactivity were urinary GAG levels and changes in liver and spleen size. Urinary GAG levels were elevated in all patients at baseline. Following 53 weeks of treatment, mean urinary GAG levels were markedly reduced in the ELAPRASE weekly group, although GAG levels still remained above the upper limit of normal in half of the ELAPRASE-treated patients. Urinary GAG levels remained elevated and essentially unchanged in the placebo group. Sustained reductions in both liver and spleen volumes were observed in the ELAPRASE weekly group through Week 53 compared to placebo. There were essentially no changes in liver and spleen volumes in the placebo group.

  • Drug Information Provided by National Library of Medicine (NLM).
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