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

NCT03485677 | Completed Phase 3 DMC

• 4 other identifiers: EFC13738U1111-1172-29502024-510751-342016-000301-37
• Study Type: interventional
• Target: 57
• Locations: 10 countries
• Sites: 21

Brief Summary

Primary Objective: Evaluated the safety and pharmacokinetics of eliglustat in pediatric participants (≥2 to \<18 years old). Secondary Objective: Evaluated the efficacy of eliglustat and quality of life in pediatric participants (≥2 to \<18 years old).

Conditions

Gaucher's Disease Type I; Gaucher's Disease Type III

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (8)

• Change in hemoglobin level

  Baseline and Week 52

• Change in platelet count

  Baseline and Week 52

• Change in liver volume

  Baseline and Week 52

• Change in spleen volume

  Baseline and Week 52

• Pulmonary disease improvement

  Baseline and Week 52

Study Arms (2)

Cohort 1: Eliglustat monotherapy

EXPERIMENTAL

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

Cohort 2: Eliglustat plus imiglucerase

EXPERIMENTAL

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; Drug: Imiglucerase GZ437843

Interventions

Eliglustat GZ385660 DRUG

Pharmaceutical form: Capsule, Liquid Route of administration: Oral

Also known as: Cerdelga

Cohort 1: Eliglustat monotherapy; Cohort 2: Eliglustat plus imiglucerase

Imiglucerase GZ437843 DRUG

Pharmaceutical form: Powder for solution for infusion Route of administration: Intravenous

Also known as: Cerezyme

Cohort 2: Eliglustat plus imiglucerase

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• The participant were 2 to \<18 years old at the time of informed consent.
• Male and female participants 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 participants had a documented negative pregnancy test prior to enrollment and throughout the study. Participants had to be willing to practice true abstinence in line with their preferred and usual lifestyle, or used a medically accepted form of contraception throughout the study.
• Cohort 1 (Eliglustat monotherapy):
• Participants must had 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. Participants had to 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):
• Participants must had 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. Participants must had 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 had to 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.

You may not qualify if:

• Substrate reduction therapy for GD within 6 months prior to enrollment.
• Partial or total splenectomy if performed within 2 years prior to enrollment
• The participant was 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 participant had any clinically significant disease other than GD.
• The participant had neurological symptoms other than oculomotor apraxia at study entry.
• The participant had received an investigational product within 30 days prior to enrollment.
• The participant was unable to receive treatment with imiglucerase due to a known hypersensitivity or was unwilling to receive imiglucerase treatment every 2 weeks.
• The participant had 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (21)

Investigational Site Number : 0320001

Buenos Aires, 1428, Argentina

Location

Investigational Site Number : 1240002

Calgary, Alberta, T3B 6A9, Canada

Location

Investigational Site Number : 1240003

Vancouver, British Columbia, V6H 3N1, Canada

Location

Investigational Site Number : 1240001

Toronto, Ontario, M5G 1X8, Canada

Location

Investigational Site Number : 2500002

Bron, 69500, France

Location

Investigational Site Number : 3800002

Rome, Roma, 00165, Italy

Location

Investigational Site Number : 3920002

Koshigaya, Saitama, 343-0845, Japan

Location

Investigational Site Number : 3920001

Tokyo, 105-8461, Japan

Location

Investigational Site Number : 6430001

Moscow, 119049, Russia

Location

Investigational Site Number : 6430004

Moscow, 119991, Russia

Location

Investigational Site Number : 6430005

Saint Petersburg, 197341, Russia

Location

Investigational Site Number : 6430002

Tomsk, 634050, Russia

Location

Investigational Site Number : 7240001

Esplugues de Llobregat, Barcelona [Barcelona], 08950, Spain

Location

Investigational Site Number : 7240002

Barakaldo, Basque Country, 48903, Spain

Location

Investigational Site Number : 7240003

Zaragoza, 50012, Spain

Location

Investigational Site Number : 7520002

Gothenburg, 416 85, Sweden

Location

Investigational Site Number : 7520001

Luleå, 971 80, Sweden

Location

Investigational Site Number : 7920004

Adana, 01300, Turkey (Türkiye)

Location

Investigational Site Number : 7920003

Istanbul, 34093, Turkey (Türkiye)

Location

Investigational Site Number : 7920002

Izmir, 35040, Turkey (Türkiye)

Location

Investigational Site Number : 8260002

Birmingham, England, B4 6NH, United Kingdom

Location

Related Links

• EFC13738 Plain Language Results Summaries

MeSH Terms

Conditions

Gaucher Disease

Interventions

eliglustat; imiglucerase

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2018
• First Posted: April 2, 2018
• Study Start: April 11, 2018
• Primary Completion: December 26, 2025
• Study Completion: December 26, 2025
• Last Updated: June 16, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); CA (3); SE (2); ES (3); AR (1); TU (3); FR (1); RU (4); IT (1); JP (2)