The purpose of this study is to evaluate the possible risks and efficacy (improvement of disease) with an experimental oral study drug named eliglustat in pediatric patients from 2 to 18 years with Gaucher disease.
ID
Source
Brief title
Condition
- Other condition
- Metabolic and nutritional disorders congenital
Synonym
Health condition
erfelijke lysosomale stofwisselingsziekte (Gaucher)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Evaluate the safety and pharmacokinetics of eliglustat in pediatric patients (2
to 18 years old).
Secondary outcome
Evaluate the efficacy of eliglustat and quality of life in pediatric patients
(2 to 18 years old).
Background summary
Gaucher disease is caused by not having the normal amount of an enzyme called
acid β-glucosidase. This enzyme*s role is to breakdown lipids, a fatty
substance in the body, called glucosylceramide. As time goes by, cells become
overloaded with glucosylceramide and become injured. This can lead to an
enlarged liver and spleen, bone problems as well as other symptoms such as
trouble breathing, reduced amount of healthy red blood cells and platelets
(blood clotting cells), tiredness, and sometimes bleeding.
Study objective
The purpose of this study is to evaluate the possible risks and efficacy
(improvement of disease) with an experimental oral study drug named eliglustat
in pediatric patients from 2 to 18 years with Gaucher disease.
Study design
Fase 3, open label, 2 treatment arms with eliglustat and imiglucerase.
Intervention
- Cohort 1: Eliglustat monotherapy: Eliglustat for two years. Cohort 1 patients
that experience significant clinical decline will receive rescue treatment.
Rescue Treatment Step 1: Switch from eliglustat to imiglucerase monotherapy.
Rescue treatment Step 2: Patients who after 6 months of rescue therapy with
imiglucerase monotherapy do not show improvement in the parameter(s) that led
to the switch from eliglustat to imiglucerase, will then receive combination
therapy with eliglustat + imiglucerase
- Cohort 2: Eliglustat plus imiglucerase Eliglustat plus imiglucerase for two
years, at the dose of enzyme replacement therapy received before enrollment.
After Week 52, Cohort 2 patients will switch to eliglustat monotherapy for the
remainder of the study if the desired clinical response has been achieved.
Study burden and risks
Risks and burdens related to blood collection, study procedures and possible
adverse events.
Paasheuvelweg 25 Paasheuvelweg 25
Amsterdam 1105 BP
NL
Paasheuvelweg 25 Paasheuvelweg 25
Amsterdam 1105 BP
NL
Listed location countries
Age
Inclusion criteria
-The patient is 6 to <18 years old at the time of informed consent.
-Male and female patients with a clinical diagnosis of Gaucher disease (GD) type 1 or type 3 with documented deficiency of acid beta-glucosidase activity by enzyme assay and glucocerebrosidase (GBA) genotype.
-Postmenarchal female patients must have a documented negative pregnancy test prior to enrollment and throughout the study. Patients must be willing to practice true abstinence in line with their preferred and usual lifestyle, or use a medically accepted form of contraception throughout the study.;Cohort 1 (Eliglustat monotherapy):
-Patients must have been receiving an enzyme replacement therapy (ERT) for a minimum of 24 months at a monthly dose equivalent to 30 U/kg to 130 U/kg of Cerezyme® (imiglucerase) with treatment ongoing at the time of enrollment. Patients must be at pre-specified treatment goals, as defined by:
-Hemoglobin level for ages 6 to <12 years: >=11.0 g/dL; for ages 12 to <18 years: >=11.0 g/dL for females and >=12.0 g/dL for males;
-Platelet count >=100,000/mm3;
-Spleen volume <10.0 multiples of normal (MN);
-Liver volume <1.5 MN;
-Absence of GD related pulmonary disease, and severe bone disease, as defined below for Cohort 2.;Cohort 2 (Eliglustat plus imiglucerase):
-Patients must have been receiving an ERT for a minimum of 36 months at a dose equivalent to at least 60 U/kg of imiglucerase every 2 weeks at the time of enrollment with treatment ongoing at the time of enrollment and the dose stable for at least the 6 months preceding enrollment. Patients must have severe clinical manifestations of GD, as defined by the presence of at least of the following:
-GD related pulmonary disease such as interstitial lung disease (ILD). The diagnosis of ILD must be confirmed by the presence of reticulonodular densities on chest X-ray.
AND/OR
-Symptomatic bone disease characterized by pathological fracture, osteonecrosis, osteopenia/osteoporosis, or bone crisis occurring in the 12 months prior to enrollment.
AND/OR
-Persistent thrombocytopenia (<80,000/mm3) related to GD.
Exclusion criteria
-Substrate reduction therapy for GD within 6 months prior to enrollment
-Partial or total splenectomy if performed within 2 years prior to enrollment
-The patient is transfusion dependent, a history of esophageal varices or liver infarction, elevated liver enzymes, significant congenital cardiac defect, coronary artery disease or left sided heart failure; clinically significant arrhythmias or conduction defect such as Type 2 second degree or third degree atrioventricular (AV) block, complete bundle branch block, prolonged QTc interval, or sustained ventricular tachycardia (VT).
-The patient has any clinically significant disease other than GD.
-The patient has neurological symptoms other than oculomotor apraxia at study entry.
-The patient has received an investigational product within 30 days prior to enrollment.
-The patient is unable to receive treatment with imiglucerase due to a known hypersensitivity or is unwilling to receive imiglucerase treatment every 2 weeks.
-The patient has a known hereditary galactose intolerance, Lapp lactase deficiency or glucose galactose malabsorption, or is a CYP2D6 ultra-rapid metabolizer or indeterminate metabolizer.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 2016-000301-37 |
| EudraCT | EUCTR2016-000301-37-NL |
| CCMO | NL65913.018.18 |