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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genzyme Corp.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

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

Trial duration

26 Mar 2019 → 26 Dec 2025

Decision date (initial)

2024-05-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Genzyme Corporation

External identifiers

EU CT number

2024-510751-34-00

EudraCT number

2016-000301-37

WHO UTN

U1111-1172-2950

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Pharmacodynamic, Efficacy, Safety, Therapy, Pharmacokinetic

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

Secondary objectives 1

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

Conditions and MedDRA coding

Gaucher's disease type I; Gaucher's disease type III

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-000461-PIP02-11

Plan to share 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​

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. -The patient is 2 to <18 years old at the time of informed consent.
2. -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.
3. -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.
4. -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.
5. -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 8

1. -Substrate reduction therapy for GD within 6 months prior to enrollment
2. -Partial or total splenectomy if performed within 2 years prior to enrollment
3. -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).
4. -The patient has any clinically significant disease other than GD.
5. -The patient has neurological symptoms other than oculomotor apraxia at study entry.
6. -The patient has received an investigational product within 30 days prior to enrollment.
7. -The patient is unable to receive treatment with imiglucerase due to a known hypersensitivity or is unwilling to receive imiglucerase treatment every 2 weeks.
8. -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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

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

Secondary endpoints 8

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genzyme Corp.

Sponsor organisation

Genzyme Corp.

Address

450 Water Street

City

Cambridge

Postcode

02141-2288

Country

United States

Scientific contact point

Organisation

Genzyme Corp.

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Genzyme Corp.

Contact name

Clinical Sciences and Operations

Third parties 9

Locations

3 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications