a multicenter, safety and efficacy study of taliglucerase alfa in subjects with type 3 gaucher disease

Conditions: Gaucher Disease, Type 3

Summary: this is a multicenter study to assess the safety and efficacy of taliglucerase alfa (60 units/kg) in previously untreated subjects of any age with type 3 gd. subjects will receive an infusion of taliglucerase alfa every 2 weeks for 12 months. subjects who tolerate the infusions well, and who are treated in centers where home therapy is the soc will be allowed to switch from site to home treatment at the discretion of the pi but after no less than 3 uneventful infusions at the site.

patients with type 3 gd exhibit both visceral and neurologic manifestations. in addition to the progressive neurologic involvement, somatic disease manifestations, especially splenomegaly and resulting cytopenia, contribute to significant mortality and morbidity . the effects of enzyme replacement therapy (ert) on patients with type 1 gd have been clearly documented and have a beneficial effect on visceral and hematologic disease parameters . it is known that recombinant enzyme does not pass the blood-brain barrier and has no effect on neurologic involvement . probably due to the rarity of type 3 gd, information on the somatic effects of ert is largely limited to case reports or single-center series. there are also few reviews of cohorts but the clinical subtype, age, genotype, ert dosage, accompanying therapies, and treatment response vary widely among patients in these cohorts. this prospective study aims to objectively evaluate the hematologic and visceral effects of ert with taliglucerase alfa on a rather clinically and genetically homogenous group of treatment-naïve patients with type 3 gd . for the purposes of this study, subjects receiving no gaucher-specific medications for at least 12 months will be considered "untreated". the results of this study are expected to provide a more objective view of the degree of response of this patient type, and potentially create new areas of research.

Eligibility criteria:
inclusion criteria: 1. male or female of any age; however, if female: * must be using contraception if of childbearing potential or must be surgically sterile * must not be lactating 2. diagnosis of type 3 gd by enzyme and sequence analysis; and confirmed by the medical monitor. 3. splenomegaly at least 5 x multiples of normal (mn). 4. treatment-naïve. exclusion criteria: eligible subjects may not have any of the following exclusion criteria: 1. type 2 gd. 2. presence of myoclonic seizures. 3. at least one allele of: * n370s (n409s in recent nomenclature) * r496h (r535h in recent nomenclature) 4. presence of calcification in heart valves or arteries in echocardiography. 5. presence of untreated iron, folic acid, vitamin b12 deficiency and/or hypothyroidism. (resolved anemia is not an exclusion criterion.) 6. presence of human immunodeficiency virus (hiv), hepatitis b surface antigen (hbsag), and/or hepatitis c infections. 7. splenectomy and bone marrow transplantation. 8. presence of any medical, emotional, behavioural, or psychological condition that in the judgment of the investigator would interfere with the subject's compliance with the requirements of the study. 9. any other disorder that may interfere with the results of the efficacy endpoints. 10. pregnancy or breastfeeding. 11. currently taking another investigational drug for any condition or any therapeutic drug for gaucher disease. 12. the subject and/or subject's parent(s) or legal guardian(s) are unable to understand the nature, scope, and possible consequences of the study. 13. medical history of any food/drugs allergy.