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

Primary Purpose

Gaucher's Disease Type I, Gaucher's Disease Type III

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Eliglustat GZ385660
Imiglucerase GZ437843
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gaucher's Disease Type I

Eligibility Criteria

2 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number :0320001
  • Investigational Site Number :1240002
  • Investigational Site Number :1240003
  • Investigational Site Number :1240001
  • Investigational Site Number :2500002
  • Investigational Site Number :3800002
  • Investigational Site Number :3920002
  • Investigational Site Number :3920001
  • Investigational Site Number :6430001
  • Investigational Site Number :6430004
  • Investigational Site Number :6430005
  • Investigational Site Number :6430002
  • Investigational Site Number :7240002
  • Investigational Site Number :7240001
  • Investigational Site Number :7240003
  • Investigational Site Number :7520002
  • Investigational Site Number :7520001
  • Investigational Site Number :8260002

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort 1: Eliglustat monotherapy

Cohort 2: Eliglustat plus imiglucerase

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Assessment of pharmacokinetic (PK) parameter of eliglustat: Cmax
Maximum concentration (Cmax) of eliglustat in plasma
Assessment of PK parameter of eliglustat: AUC
Area under the plasma eliglustat concentration-time curve (AUC)
Adverse Events
Number of adverse events in pediatric patients

Secondary Outcome Measures

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

Full Information

First Posted
March 23, 2018
Last Updated
July 20, 2023
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT03485677
Brief Title
Safety and Efficacy of Eliglustat With or Without Imiglucerase in Pediatric Patients With Gaucher Disease (GD) Type 1 and Type 3
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 20, 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 11, 2018 (Actual)
Primary Completion Date
November 20, 2025 (Anticipated)
Study Completion Date
November 20, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gaucher's Disease Type I, Gaucher's Disease Type III

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: Eliglustat monotherapy
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2: Eliglustat plus imiglucerase
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Eliglustat GZ385660
Other Intervention Name(s)
Cerdelga
Intervention Description
Pharmaceutical form: Capsule, Liquid Route of administration: Oral
Intervention Type
Drug
Intervention Name(s)
Imiglucerase GZ437843
Other Intervention Name(s)
Cerezyme
Intervention Description
Pharmaceutical form: Powder for solution for infusion Route of administration: Intravenous
Primary Outcome Measure Information:
Title
Assessment of pharmacokinetic (PK) parameter of eliglustat: Cmax
Description
Maximum concentration (Cmax) of eliglustat in plasma
Time Frame
Weeks 2, 13, 26 and 52
Title
Assessment of PK parameter of eliglustat: AUC
Description
Area under the plasma eliglustat concentration-time curve (AUC)
Time Frame
Weeks 2 and 52
Title
Adverse Events
Description
Number of adverse events in pediatric patients
Time Frame
Up to Week 364
Secondary Outcome Measure Information:
Title
Change in hemoglobin level
Description
Absolute change from baseline for hemoglobin (g/dL) (Cohort 1 patients)
Time Frame
Baseline and Week 52
Title
Change in platelet count
Description
Percent change from baseline for platelet count (Cohort 1 patients)
Time Frame
Baseline and Week 52
Title
Change in liver volume
Description
Percent change from baseline for liver volume (Cohort 1 patients)
Time Frame
Baseline and Week 52
Title
Change in spleen volume
Description
Percent change from baseline for spleen volume (Cohort 1 patients)
Time Frame
Baseline and Week 52
Title
Pulmonary disease improvement
Description
Proportion of patients with improvement in pulmonary disease (Cohort 2 patients)
Time Frame
Baseline and Week 52
Title
Bone disease improvement
Description
Proportion of patients with improvement in bone disease (Cohort 2 patients)
Time Frame
Baseline and Week 52
Title
Thrombocytopenia
Description
Proportion of patients with improvement in thrombocytopenia (Cohort 2 patients)
Time Frame
Baseline and Week 52
Title
Quality of Life
Description
Health-related quality of life will be measured by the Pediatric Quality of Life Inventory™ (PedsQL™) questionnaires
Time Frame
Baseline and Week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number :0320001
City
Capital Federal
State/Province
Buenos Aires
ZIP/Postal Code
C1425DUC
Country
Argentina
Facility Name
Investigational Site Number :1240002
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T3B 6A8
Country
Canada
Facility Name
Investigational Site Number :1240003
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6H 3V4
Country
Canada
Facility Name
Investigational Site Number :1240001
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Investigational Site Number :2500002
City
BRON Cedex
ZIP/Postal Code
69677
Country
France
Facility Name
Investigational Site Number :3800002
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Investigational Site Number :3920002
City
Koshigaya-shi
State/Province
Saitama
ZIP/Postal Code
343-8555
Country
Japan
Facility Name
Investigational Site Number :3920001
City
Minato-ku
State/Province
Tokyo
ZIP/Postal Code
105-8471
Country
Japan
Facility Name
Investigational Site Number :6430001
City
Moscow
ZIP/Postal Code
119049
Country
Russian Federation
Facility Name
Investigational Site Number :6430004
City
Moscow
ZIP/Postal Code
119991
Country
Russian Federation
Facility Name
Investigational Site Number :6430005
City
St-Petersburg
ZIP/Postal Code
197341
Country
Russian Federation
Facility Name
Investigational Site Number :6430002
City
Tomsk
ZIP/Postal Code
634050
Country
Russian Federation
Facility Name
Investigational Site Number :7240002
City
Barakaldo
State/Province
Bizkaia
ZIP/Postal Code
48903
Country
Spain
Facility Name
Investigational Site Number :7240001
City
Esplugues de Llobregat
State/Province
Catalunya [Cataluña]
ZIP/Postal Code
08950
Country
Spain
Facility Name
Investigational Site Number :7240003
City
Zaragoza
ZIP/Postal Code
50006
Country
Spain
Facility Name
Investigational Site Number :7520002
City
Göteborg
ZIP/Postal Code
416 85
Country
Sweden
Facility Name
Investigational Site Number :7520001
City
Luleå
ZIP/Postal Code
97180
Country
Sweden
Facility Name
Investigational Site Number :8260002
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

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

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