Safety and Efficacy of Eliglustat with or without Imiglucerase in Pediatric Patients with Gaucher Disease (GD) Type 1 and Type 3

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2016-000301-37-ES
• Date of registration: 06/07/2018
• Prospective Registration: No
• Primary sponsor: Genzyme Corporation
• Public title: Safety and Efficacy of Eliglustat with or without Imiglucerase in Pediatric Patients with Gaucher Disease (GD) Type 1 and Type 3
• Scientific title: Open label, Two Cohort (with and without Imiglucerase), Multicenter Study to Evaluate Pharmacokinetics, Safety, and Efficacy of Eliglustat in Pediatric Patients with Gaucher Disease Type 1 and Type 3 - ELIKIDS
• Date of first enrolment: 21/06/2018
• Target sample size: 120
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000301-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Canada, Egypt, France, Italy, Netherlands, Russian Federation, Spain, Sweden, Turkey, United Kingdom

Contacts

• Name: Unidad Estudios Clínicos
• Affiliation: sanofi-aventis, s.a.

• Name: Unidad Estudios Clínicos
• Affiliation: sanofi-aventis, s.a.

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 120
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Congenital, hereditary and neonatal diseases
MedDRA version: 20.0 Level: PT Classification code 10075697 Term: Gaucher's disease type I System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 20.0 Level: PT Classification code 10075699 Term: Gaucher's disease type III System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Trade Name: Cerdelga
Product Name: Eliglustat
Product Code: GZ385660
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Eliglustat
Current Sponsor code: GZ385660
Other descriptive name: ELIGLUSTAT TARTRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 84-

Trade Name: Cerezyme
Product Name: Imiglucerase
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: IMIGLUCERASE
CAS Number: 154248-97-2
Other descriptive name: Cerezyme
Concentration unit: U unit(s)
Concentration type: equal
Concentration number: 400-

Product Name: Eliglustat
Product Code: GZ385660
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Eliglustat
Current Sponsor code: GZ385660
Other descriptive name: ELIGLUSTAT TARTRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 21-

Product Name: Eliglustat
Product Code: GZ385660
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Eliglustat
Current Sponsor code: GZ385660
Other descriptive name: ELIGLUSTAT TARTRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 42-

Primary Outcome(s)

Primary end point(s): 1- Maximum concentration (Cmax) of eliglustat in plasma.
2- Area under the plasma eliglustat concentration-time curve (AUC)
3- Number of adverse events in pediatric patients

Timepoint(s) of evaluation of this end point: 1- Maximum concentration (Cmax) of eliglustat in plasma : Weeks 2, 13, 26 and 52
2- Area under the plasma eliglustat concentration-time curve (AUC) : Weeks 2 and 52
3- Number of adverse events in pediatric patients : Up to Week 104

Secondary Objective: Evaluate the efficacy of eliglustat and quality of life in pediatric patients (=6 to <18 years old).

Main Objective: Evaluate the safety and pharmacokinetics of eliglustat in pediatric patients (=6 to <18 years old).

Secondary Outcome(s)

Secondary end point(s): 1- Absolute change from baseline for hemoglobin (g/dL) (Cohort 1 patients)
2- Percent change from baseline for platelet count (Cohort 1 patients)
3- Percent change from baseline for liver volume (Cohort 1 patients)
4- Percent change from baseline for spleen volume (Cohort 1 patients)
5- Proportion of patients with improvement in pulmonary disease (Cohort 2 patients)
6- Proportion of patients with improvement in bone disease (Cohort 2 patients)
7- Proportion of patients with improvement in thrombocytopenia (Cohort 2 patients)
8- Health-related quality of life will be measured by the Pediatric Quality of Life InventoryTM (PedsQLTM) questionnaires.

Timepoint(s) of evaluation of this end point: Baseline and Week 52

Secondary ID(s)

EFC13738

2016-000301-37-NL

Source(s) of Monetary Support

Genzyme Corporation