Pharmacokinetics, Safety, and Efficacy of Eliglustat With or Without Imiglucerase in Pediatric Gaucher Disease Types 1 and 3: A Multicenter Study

The primary objective of this study is to evaluate the **safety** and pharmacokinetics of **eliglustat** in pediatric patients aged 2 to less than 18 years with Gaucher disease type 1 and type 3. This is clinically relevant as it aims to ensure that the treatment is both safe and effectively metabolized in this specific patient population, which is crucial for optimizing therapeutic outcomes and minimizing potential adverse effects.

Secondary objectives include evaluating the efficacy of eliglustat and assessing the quality of life in the same pediatric cohort. These objectives are important for understanding the overall impact of the treatment on disease progression and patient well-being, providing a comprehensive view of the treatment's benefits beyond its pharmacokinetic profile.

The clinical trial involves a total of **46 participants** diagnosed with **Gaucher's disease type I** or **type III**. The study population consists of pediatric patients aged 2 to less than 18 years, including both male and female subjects. Participants were selected based on a confirmed clinical diagnosis of Gaucher disease with documented deficiency of acid beta-glucosidase activity and glucocerebrosidase (GBA) genotype. The trial includes patients who have been receiving enzyme replacement therapy (ERT) for a specified duration and dosage, with treatment ongoing at the time of enrollment. Lifestyle considerations include the requirement for postmenarchal female patients to have a negative pregnancy test and to practice abstinence or use contraception. The trial population is considered vulnerable due to the pediatric nature of the participants. Key inclusion criteria involve specific hematological and organ volume parameters, as well as the absence of severe Gaucher disease-related complications for certain cohorts. The study aims to evaluate the safety and pharmacokinetics of eliglustat in this demographic.

The clinical trial is designed to evaluate the **safety** and pharmacokinetics of **eliglustat** in pediatric patients aged 2 to less than 18 years with Gaucher disease type 1 and type 3. This is an open-label, two-cohort, multicenter study involving patients who will either receive eliglustat monotherapy or a combination of eliglustat and **imiglucerase**. The trial is structured as a Phase 5 study, with a focus on assessing the maximum concentration (Cmax) and area under the curve (AUC) of eliglustat in plasma, alongside monitoring adverse events. The study is expected to run from February 2019 to November 2025, with participant involvement lasting up to 364 days.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, clinical diagnosis of Gaucher disease, and specific treatment history. The inclusion criteria require patients to have documented deficiency of acid beta-glucosidase activity and a stable treatment regimen with enzyme replacement therapy (ERT) for a specified duration. The trial includes follow-up visits to monitor pharmacokinetic parameters, safety, and efficacy outcomes, such as changes in hemoglobin levels, platelet counts, and organ volumes. The end-of-study visit will conclude the trial for each participant, assessing the overall impact of the treatment regimen.

Participants may be withdrawn from the study if they experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The trial aims to provide comprehensive data on the therapeutic potential of eliglustat, both as a standalone treatment and in combination with imiglucerase, in managing Gaucher disease in the pediatric population. The study's design ensures rigorous monitoring and evaluation to achieve its primary and secondary endpoints, contributing valuable insights into the treatment of this rare condition.

The clinical trial involves the administration of **Eliglustat**, a synthetic small molecule, in various pharmaceutical forms. The primary form is a **hard capsule** containing **eliglustat tartrate** as the active substance. This formulation is intended for **oral use** and is not specifically designed as a pediatric formulation. The maximum daily dose for this form is 168 mg, with a total maximum dose of 428,064 mg over a treatment period of 364 days. The capsule is manufactured by Genzyme Corporation and is identified by the sponsor product code GZ385660.

Another formulation of **Eliglustat** used in the trial is a **powder for oral suspension**, which is specifically designed as a pediatric formulation. This form also contains **eliglustat tartrate** and is administered orally. The maximum daily dose for this formulation is 252 mg, with a total maximum dose of 642,096 mg over the same treatment period of 364 days. This formulation is also produced by Genzyme Corporation and shares the same sponsor product code.

A third formulation of **Eliglustat** is a **hard capsule** designed for pediatric use, containing **eliglustat tartrate**. This form is administered orally with a maximum daily dose of 42 mg and a total maximum dose of 107,016 mg over 364 days. This pediatric formulation is also manufactured by Genzyme Corporation and is identified by the same sponsor product code.

In addition to Eliglustat, the trial includes the administration of **Cerezyme**, which contains **imiglucerase** as the active substance. Cerezyme is provided as a **powder for concentrate for solution for infusion** and is administered via **intravenous use**. The maximum daily dose is 60 IU/Kg, with a total maximum dose of 10,920 IU/Kg over 364 days. This product is manufactured by Sanofi B.V. and is used as a comparator treatment in the study. The product is relabeled and repackaged for clinical supplies, ensuring compliance with trial requirements.

The clinical trial aims to assess the efficacy of **Eliglustat** in pediatric patients with Gaucher disease type 1 and type 3. Efficacy will be evaluated through both primary and secondary endpoints. Primary endpoints include the assessment of pharmacokinetic parameters such as the maximum concentration (Cmax) of **Eliglustat** in plasma and the area under the plasma concentration-time curve (AUC). Additionally, the number of adverse events in pediatric patients will be monitored.

Secondary endpoints focus on clinical outcomes and include the absolute change from baseline in hemoglobin levels, percent change in platelet count, liver volume, and spleen volume for Cohort 1 patients. For Cohort 2 patients, the proportion of patients with improvement in pulmonary disease, bone disease, and thrombocytopenia will be assessed. Health-related quality of life will be measured using the Pediatric Quality of Life InventoryTM (PedsQLTM) questionnaires.