Evaluation of Empagliflozin for Neutropenia Management in Glycogen Storage Disease Type Ib Patients

The primary objective of this study is to evaluate the **safety** and tolerability of empagliflozin in the treatment of **neutropenia** in patients with Glycogenosis type Ib (GSD Ib). This ultra-rare disease, inherited in an autosomal recessive manner, presents significant clinical challenges, and assessing the safety profile of empagliflozin is crucial for determining its viability as a treatment option.

Secondary objectives include:

• Assessing the efficacy of empagliflozin as expressed by the restoration of neutrophil numbers and function.
• Reducing or stopping filgrastim dosing to minimize adverse effects associated with filgrastim treatment.
• Evaluating metabolic compensation in patients undergoing treatment.

The clinical trial involves participants diagnosed with **Glycogenosis type Ib**, an ultra-rare autosomal recessive disease. The study population includes both male and female subjects, with an age range starting from 4 weeks and older. Participants are required to have a biochemical and/or molecular diagnosis of Glycogenosis type Ib, accompanied by neutropenia and/or abnormal NADPH oxidase activity in neutrophils. The trial includes a vulnerable population, as it involves children, with informed consent required from legal representatives for those under 13 years of age. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that participants are suitable for evaluating the safety and tolerability of neutropenia treatment with empagliflozin. No specific lifestyle considerations such as diet or physical activity are mentioned in the trial details.

The clinical trial is designed to evaluate the **safety** and tolerability of **empagliflozin** in the treatment of neutropenia in patients with glycogenosis type Ib, an ultra-rare autosomal recessive disease. This study is a Phase 4, randomized, double-blind, controlled trial. The trial is expected to last until March 26, 2025, with recruitment having commenced on March 7, 2022. Participants will be administered **Jardiance 10 mg film-coated tablets** orally, with a maximum daily dose of 20 mg, over a treatment period of up to 24 weeks.

The study involves several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (4 weeks or older), biochemical or molecular diagnosis of glycogenosis Ib with neutropenia, and informed consent. Follow-up visits will be scheduled to monitor safety and collect data on adverse reactions, as well as to assess the efficacy of the treatment in restoring neutrophil numbers and function. The primary endpoint focuses on the safety and tolerability of empagliflozin, while the secondary endpoint evaluates its efficacy.

Participants are expected to be involved in the study for the entire duration unless conditions arise that necessitate early termination, such as significant adverse reactions or withdrawal of consent. The trial is not categorized as low intervention, and it adheres to rigorous standards to ensure the collection of reliable and valid data. The study aims to provide valuable insights into the management of neutropenia in patients with glycogenosis type Ib, contributing to the broader understanding of this rare condition.

The clinical trial involves the administration of **Jardiance** 10 mg film-coated tablets, which contain the active substance **empagliflozin**. Empagliflozin is a chemical compound classified under the pharmacotherapeutic group of antidiabetic agents, specifically hypoglycemic agents excluding insulin. The pharmaceutical form of the medication is a film-coated tablet, designed for oral administration. The dosage regimen for the trial specifies a maximum daily dose of 20 mg, with the treatment period extending up to 24 weeks. The tablets are manufactured by Boehringer Ingelheim International GmbH and are not formulated for pediatric use. The trial aims to evaluate the safety and tolerability of empagliflozin in the treatment of neutropenia in patients with Glycogen Storage Disease Type Ib (GSD Ib).

In addition to the experimental treatment, the study may include non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments, as deemed necessary by the study protocol. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial does not involve any orphan drug designation for the investigational product. The administration of the medication will be conducted under controlled conditions to assess its efficacy and safety profile in the specified patient population.

The clinical trial aims to assess the efficacy of **empagliflozin** in the treatment of neutropenia in patients with glycogen storage disease type Ib (GSD Ib). The secondary endpoint of the study is to evaluate efficacy, which will be expressed as the restoration of neutrophil numbers and function. Efficacy assessments will be conducted throughout the study period, with specific timepoints for measurement not explicitly detailed in the provided data. The trial will utilize appropriate methods to measure and analyze the restoration of neutrophil numbers and function, although specific tools or instruments are not mentioned. The study is designed to ensure that efficacy data is collected systematically and analyzed to determine the impact of empagliflozin on neutrophil restoration in the target patient population.