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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Gaucher's Disease Type III; Gaucher's Disease Type I
• Intervention / Treatment: Drug: Eliglustat GZ385660; Drug: Imiglucerase GZ437843

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, C1425DUC
      • Investigational Site Number : 0320001
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Investigational Site Number : 1240002
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Investigational Site Number : 1240003
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Investigational Site Number : 1240001
• France
  • BRON Cedex, France, 69677
    • Investigational Site Number : 2500002
• Italy
  • Roma, Italy, 00165
    • Investigational Site Number : 3800002
• Japan
  • Saitama
    • Koshigaya-shi, Saitama, Japan, 343-8555
      • Investigational Site Number : 3920002
  • Tokyo
    • Minato-ku, Tokyo, Japan, 105-8471
      • Investigational Site Number : 3920001
• Russian Federation
  • Moscow, Russian Federation, 119049
    • Investigational Site Number : 6430001
  • Moscow, Russian Federation, 119991
    • Investigational Site Number : 6430004
  • St-Petersburg, Russian Federation, 197341
    • Investigational Site Number : 6430005
  • Tomsk, Russian Federation, 634050
    • Investigational Site Number : 6430002
• Spain
  • Zaragoza, Spain, 50006
    • Investigational Site Number : 7240003
  • Bizkaia
    • Barakaldo, Bizkaia, Spain, 48903
      • Investigational Site Number : 7240002
  • Catalunya [Cataluña]
    • Esplugues de Llobregat, Catalunya [Cataluña], Spain, 08950
      • Investigational Site Number : 7240001
• Sweden
  • Göteborg, Sweden, 416 85
    • Investigational Site Number : 7520002
  • Luleå, Sweden, 97180
    • Investigational Site Number : 7520001
• Turkey
  • Adana, Turkey, 01300
    • Investigational Site Number : 7920004
  • Istanbul, Turkey, 34093
    • Investigational Site Number : 7920003
  • Izmir, Turkey, 35040
    • Investigational Site Number : 7920002
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Investigational Site Number : 8260002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 15 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Eliglustat monotherapy; Eliglustat for at least 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.	Drug: Eliglustat GZ385660; Pharmaceutical form: Capsule, Liquid Route of administration: Oral; Other Names: Cerdelga
Experimental: Cohort 2: Eliglustat plus imiglucerase; Eliglustat plus imiglucerase for three 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.	Drug: Eliglustat GZ385660; Pharmaceutical form: Capsule, Liquid Route of administration: Oral; Other Names: Cerdelga; Drug: Imiglucerase GZ437843; Pharmaceutical form: Powder for solution for infusion Route of administration: Intravenous; Other Names: Cerezyme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of pharmacokinetic (PK) parameter of eliglustat: Cmax	Maximum concentration (Cmax) of eliglustat in plasma	Weeks 2, 13, 26 and 52
Assessment of PK parameter of eliglustat: AUC	Area under the plasma eliglustat concentration-time curve (AUC)	Weeks 2 and 52
Adverse Events	Number of adverse events in pediatric patients	Up to Week 364

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hemoglobin level	Absolute change from baseline for hemoglobin (g/dL) (Cohort 1 patients)	Baseline and Week 52
Change in platelet count	Percent change from baseline for platelet count (Cohort 1 patients)	Baseline and Week 52
Change in liver volume	Percent change from baseline for liver volume (Cohort 1 patients)	Baseline and Week 52
Change in spleen volume	Percent change from baseline for spleen volume (Cohort 1 patients)	Baseline and Week 52
Pulmonary disease improvement	Proportion of patients with improvement in pulmonary disease (Cohort 2 patients)	Baseline and Week 52
Bone disease improvement	Proportion of patients with improvement in bone disease (Cohort 2 patients)	Baseline and Week 52
Thrombocytopenia	Proportion of patients with improvement in thrombocytopenia (Cohort 2 patients)	Baseline and Week 52
Quality of Life	Health-related quality of life will be measured by the Pediatric Quality of Life Inventory™ (PedsQL™) questionnaires	Baseline and Week 52

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2018
• Primary Completion (Estimated): November 20, 2025
• Study Completion (Estimated): November 20, 2025

Study Registration Dates

• First Submitted: March 23, 2018
• First Submitted That Met QC Criteria: March 23, 2018
• First Posted (Actual): April 2, 2018

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Disease; Gaucher Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Eliglustat
• Other Study ID Numbers: EFC13738; 2016-000301-37 (EudraCT Number); U1111-1172-2950 (Registry Identifier: ICTRP); 2024-510751-34 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No