Safety and Efficacy of Empagliflozin in GSD1b Patients With Neutropenia (EMPAtia)

Evaluation of Efficacy and Safety of Empagliflozin in Treatment of Neutropenia in Patients With Glycogenosis Ib

Treatment of neutropenia of Glycogenosis type 1b patients with empagliflozin

Study Overview

• Status: Not yet recruiting
• Conditions: Glucose 6 Phosphatase Deficiency
• Intervention / Treatment: Drug: Empagliflozin

Detailed Description

Symptoms of glycogen storage disease type Ib (GSD Ib) include - among others - hypoglycemia, hepatomegaly and neutropenia with concomitant neutrophil dysfunction, which results in recurrent bacterial and fungal infections, and inflammatory bowel disease.

At present filgrastim is the only available drug to treat neutropenia in GSD Ib patients; it stimulates neutrophil production, but doesn't restore their function. Part of GSD Ib patients doesn't respond to filgrastim treatment. The latest research results showed, that neutropenia and neutrophil dysfunction in GSD Ib patients are results of extensive accumulation of 1,5-anhydroglucitol-phosphate. Empagliflozin, a SGLT2 inhibitor, inhibits renal glucose and 1,5-anhydroglucitol reabsorption and is an effective and safe method of treatment of neutropenia in this group of patients. Empagliflozin (Jardiance®) is a drug, which is registered in Poland to treat type II diabetes in adults. The aim of our study is to evaluate the efficacy and safety of neutropenia in patients with GSD Ib with empagliflozin (Jardiance®).

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Poland
  • Warsaw, Poland, 04-730
    • The Children's Memorial Health Institute
    • Contact: Magdalena Kaczor, MD; Phone Number: +48227494; Email: mwojtylo@o2.pl
    • Principal Investigator: Dariusz Rokicki, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Minimum age 4 weeks old female Or Male
• GSD1b confirmed by genetic analysis with neutropenia and/or reduced respiratory burst
• Informed consent signed by the parents/assigns, and the recipient (>13 years old)

Exclusion Criteria:

• Risk of non-compliance
• Chronic renal diseases (eGFR < 60 ml/min/1,73 m2)
• Active urinary tract infection (temporal criterion, up to recovery)
• Participation in another clinical trial (minimum 6 months from the end of participation until the date of signing the Informed Consent Form)
• Participation in therapeutic experiment, in addition to the experimental treatment with empagliflozin (minimum 12 months from the end of participation until the date of signing the Informed Consent Form)
• Pregnancy, breastfeeding
• Allergy to Empagliflozin
• Lack of informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: oral administration of Empagliflozin	Drug: Empagliflozin; dosis depending on body weight: <20 kg 5 mg 1x/day; 20-40 kg 2 x 5 mg; >40 kg 2 x 10 mg; Other Names: Jardiance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Empaglifozin safety and tolerability measured by occurrence of adverse reactions	Empaglifozin saftey and tolerability measured by occurrence of adverse reactions	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of neutropenia treatment measured as percentage of the patients	who achieved >500 neutrophils/ml for at least 6 months with normalization of oxidative burst with decrease of bacterial and fungal infections compared to the period before study with decrease of hospitalization number with decrease of the number of defecation, gingival sores, and calprotectin average concentration in stool	2 years
Dosis change/withdrawal of filgrastrim	Dosis change/withdrawal of filgrastrim	2 years
Degree of metabolic compensation	measured as change of triglycerides (mg/dL), lactate (mg/dL), and uric acid (mg/dL) compared to the period before study	2 years

Collaborators and Investigators

• Sponsor: Children's Memorial Health Institute, Poland
• Collaborators: Department of Internal Medicine, Hypertension and Vascular Diseases, The Medical University of Warsaw

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2021
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): March 1, 2025

Study Registration Dates

• First Submitted: June 11, 2021
• First Submitted That Met QC Criteria: June 11, 2021
• First Posted (Actual): June 18, 2021

Study Record Updates

• Last Update Posted (Actual): June 23, 2021
• Last Update Submitted That Met QC Criteria: June 18, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Agranulocytosis; Leukopenia; Leukocyte Disorders; Glycogen Storage Disease; Neutropenia; Glycogen Storage Disease Type I; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: EMPAtia; 2021-000580-78 (EudraCT Number)

Drug and device information, study documents

• 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