Pharmacokinetics, Pharmacodynamics And Safety Study Of Elelyso(tm) In Pediatric Subjects With Type 1 Gaucher Disease

Overview

In August of 2014, the FDA approved ELELYSO for long-term enzyme replacement therapy (ERT) for pediatric subjects with a confirmed diagnosis of Type 1 Gaucher disease. The recommended dosage for treatment-naïve adult and pediatric subjects 4 years of age and older is 60 units per kg of body weight administered every other week as a 60 to 120 minute intravenous infusion. As a postmarketing commitment, the Sponsor agreed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of Elelyso (taliglucerase alfa) in pediatric subjects with Type 1 Gaucher Disease. in at least 5 subjects with body weight less than 15 kg; at least 5 subjects with body weight 15 to less than 20 kg; and at least 5 subjects with body weight of 20-25 kg with Type 1 Gaucher disease dosed at 60 units/kg every other week. When applicable, PD measurements for children enrolled in the PK study may be obtained through the taliglucerase alfa registry (PMR 1895-5) and will include organ volumes (spleen and liver), hematological values (hemoglobin and platelets) as well as growth (height and weight) data. Safety data, including any serious hypersensitivity reactions, such as anaphylaxis, as well as changes in antibody status (ie, detection and titers of binding and neutralizing antibodies, and detection of IgE antibodies), will also be collected through the taliglucerase alfa registry.

This study (B3031003) is an open-label study in pediatric subjects with Type 1 Gaucher Disease to characterize PK, PD and safety following an infusion of taliglucerase alfa in at least 5 subjects with body weight less than 15 kg; at least 5 subjects with body weight 15 to less than 20 kg; and at least 5 subjects with body weight of 20-25 kg. The PK sample collection will take approximately 4 hours to complete and will be performed one month or up to 6 months after the subject's first taliglucerase infusion in the registry study. The subject will be contacted the day after the PK samples are collected to assess any continuing or new adverse events and to review the subject's concomitant medications. Body weight at the time of the PK blood draw will determine the weight category for each subject. Subjects enrolled into the study will be assigned the same unique subject number assigned to them in the registry study (B3031002). This will allow linkage to relevant data from the registry study for analysis in this study. For the purposes of this study, baseline evaluations will be obtained from the registry study and must be performed prior to the subject's first dose of taliglucerase alfa. The Month 6 and Month 12 evaluations will be performed 6 months and 12 months after the start of taliglucerase alfa treatment, respectively. Subjects will be eligible for the PK study (B3031003) only if the PD assessments (spleen volume/size, hemoglobin/platelet counts and height/weight measurements) immunogenicity data and Gaucher disease diagnostic history are available from the registry study baseline visit and prior to the start of taliglucerase alfa treatment. If liver volume/size is available, it will also be analyzed but is not necessary for eligibility for the PK study. Pediatric subjects prescribed 60 units/kg of taliglucerase alfa every other week by their physician will be recruited from the registry study. Subjects can be screened for the PK study at the same time as they are enrolled into the registry study (ERT treatment-naïve subjects) or up to 6 months after they are enrolled into the registry study (previously ERT naïve subjects) if PD assessments (spleen volume/size, hemoglobin/platelet counts and height/weight measurements), immunogenicity data and Gaucher disease diagnostic history (residual enzyme activity and genotype data) were performed at baseline of the registry study and prior to the start of taliglucerase alfa treatment. Baseline data from the registry study for PD and immunogenicity testing are defined as PD measurements (spleen volume/size, liver volume/size (if available), hemoglobin and platelet counts and growth measures), Gaucher disease diagnostic history and immunogenicity samples that were collected at entry into the registry study and prior to the start of taliglucerase alfa treatment. For the secondary PD endpoints, spleen volume/size and liver volume/size (if available) will be measured using MRI, CT or ultrasound, whichever is the standard of care according to the investigator. The method used to measure spleen and liver volume/size at Baseline will be the same one used at Month 12. Change from Baseline and percent change from Baseline at Month 12 of registry study will be calculated for spleen volume, liver volume (if available), hemoglobin and platelet counts, and growth measures (height, weight and Z-scores). For each subject enrolled in this study, safety data while on taliglucerase alfa, starting from the baseline visit (entry into the registry study) and continuing until 28 days after the Month 12 PD data collection visit, will be obtained for reporting. Safety assessments for the study will include collection of all adverse event and serious adverse event data, including serious hypersensitivity reactions, procedures for immunogenicity testing (ie, detection and titers of binding and neutralizing antibodies and detection of IgE antibodies) as well as vital signs taken as standard of care during infusions. A pre-dose blood sample for testing of antidrug antibodies (ADA) on the day of PK Sample Visit will be collected in an effort to assess the impact of immunogenicity on PK.