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

Gaucher's Disease Type I Clinical Trial

— ELIKIDS  

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03485677
• Other study ID #: EFC13738
• Secondary ID: U1111-1172-29502
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 11, 2018
• Est. completion date: November 20, 2025

Study information

• Verified date: February 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

Evaluate the safety and pharmacokinetics of eliglustat in pediatric patients (≥2 to <18 years old).

Secondary Objective:

Evaluate the efficacy of eliglustat and quality of life in pediatric patients (≥2 to <18 years old).

Description:

The study will include a screening period of up to 60 days (Day -60 to -1), a primary analysis treatment period (Day 1 to Week 52), a long-term treatment period (Week 53 to Week 104), and an extension period continuing up to Week 364 (for patients who continue to demonstrate the clinical benefit from eliglustat monotherapy at Week 104). After study completion, patients will be encouraged to enroll in the International Collaborative Gaucher Group (ICGG) Gaucher Registry.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 57
• Est. completion date: November 20, 2025
• Est. primary completion date: November 20, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

Inclusion criteria :

• The patient is 2 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 2 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, or at the maximum dose locally approved, 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 one 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.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Disease
• Gaucher Disease
• Gaucher's Disease Type I
• Gaucher's Disease Type III

Intervention

Drug:
• Eliglustat GZ385660
Pharmaceutical form: Capsule, Liquid Route of administration: Oral
• Imiglucerase GZ437843
Pharmaceutical form: Powder for solution for infusion Route of administration: Intravenous

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320001	Capital Federal	Buenos Aires
Canada	Investigational Site Number : 1240002	Calgary	Alberta
Canada	Investigational Site Number : 1240001	Toronto	Ontario
Canada	Investigational Site Number : 1240003	Vancouver	British Columbia
France	Investigational Site Number : 2500002	BRON Cedex
Italy	Investigational Site Number : 3800002	Roma
Japan	Investigational Site Number : 3920002	Koshigaya-shi	Saitama
Japan	Investigational Site Number : 3920001	Minato-ku	Tokyo
Russian Federation	Investigational Site Number : 6430001	Moscow
Russian Federation	Investigational Site Number : 6430004	Moscow
Russian Federation	Investigational Site Number : 6430005	St-Petersburg
Russian Federation	Investigational Site Number : 6430002	Tomsk
Spain	Investigational Site Number : 7240002	Barakaldo	Bizkaia
Spain	Investigational Site Number : 7240001	Esplugues de Llobregat	Catalunya [Cataluña]
Spain	Investigational Site Number : 7240003	Zaragoza
Sweden	Investigational Site Number : 7520002	Göteborg
Sweden	Investigational Site Number : 7520001	Luleå
Turkey	Investigational Site Number : 7920004	Adana
Turkey	Investigational Site Number : 7920003	Istanbul
Turkey	Investigational Site Number : 7920002	Izmir
United Kingdom	Investigational Site Number : 8260002	Birmingham

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of pharmacokinetic (PK) parameter of eliglustat: Cmax	Maximum concentration (Cmax) of eliglustat in plasma	Weeks 2, 13, 26 and 52
Primary	Assessment of PK parameter of eliglustat: AUC	Area under the plasma eliglustat concentration-time curve (AUC)	Weeks 2 and 52
Primary	Adverse Events	Number of adverse events in pediatric patients	Up to Week 364
Secondary	Change in hemoglobin level	Absolute change from baseline for hemoglobin (g/dL) (Cohort 1 patients)	Baseline and Week 52
Secondary	Change in platelet count	Percent change from baseline for platelet count (Cohort 1 patients)	Baseline and Week 52
Secondary	Change in liver volume	Percent change from baseline for liver volume (Cohort 1 patients)	Baseline and Week 52
Secondary	Change in spleen volume	Percent change from baseline for spleen volume (Cohort 1 patients)	Baseline and Week 52
Secondary	Pulmonary disease improvement	Proportion of patients with improvement in pulmonary disease (Cohort 2 patients)	Baseline and Week 52
Secondary	Bone disease improvement	Proportion of patients with improvement in bone disease (Cohort 2 patients)	Baseline and Week 52
Secondary	Thrombocytopenia	Proportion of patients with improvement in thrombocytopenia (Cohort 2 patients)	Baseline and Week 52
Secondary	Quality of Life	Health-related quality of life will be measured by the Pediatric Quality of Life Inventory™ (PedsQL™) questionnaires	Baseline and Week 52