Empagliflozin as a Treatment for Severe Congenital Neutropenia Due to G6PC3 Deficiency

NCT05078879 | Completed Phase 1

• 2 other identifiers: 10000236000236-I
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Severe congenital neutropenia (SCN) is an immune system disease. People with SCN do not have enough of a kind of white blood cell called neutrophils. This means they get sick easily from infections. Some drugs to treat SCN have lots of side effects. Researchers want to see if a the drug empagliflozin can help increase the number of neutrophils in a person with SCN. Objective: To see if a drug called empagliflozin can help people with SCN. Eligibility: Adults aged 18 and older with SCN. Design: Participants will be screened with a physical exam, medical history, and blood tests. They may have a pregnancy test. Participants will have study visits and local lab visits. They will repeat the screening tests. They will have heart and lung function tests. They will have an ultrasound of the liver and spleen. Their skin symptoms will be photographed. They may have consultations with specialists. They may give a stool sample. They may have an optional colonoscopy with tissue sample collection. They may have an optional bone marrow biopsy and aspirate. They may have an optional magnetic resonance imaging scan of their heart. Participants will be admitted to NIH for 5 7 days. They will start taking the study drug as a pill once daily. They will be monitored for side effects. Participants will take the study drug at home for 12 months. They will use a fingerstick blood glucose meter to measure blood sugar at home. Participants may be able to take the study drug through their local doctor after the study ends. Participation will last for 15 months.

Conditions

Crohn's Disease; Glycogen Metabolism; Inflammatory Bowel Disease (IBD)

Keywords

Glycogen metabolism; Jardiance; Inflammatory Bowe Disease (IBD); G6PT deficiency; 1,5-AG

Outcome Measures

Primary Outcomes (2)

• Absolute Neutrophil Count

  ANC increase by \>500 cells/uL over baseline (measured at least 3x over 2 days)

  End of Treatment at 12 months

• Safety

  No Grade 3/4 toxicities that require pause of the study drug.

  End of Treatment at 12 months

Secondary Outcomes (1)

• Neutrophil Function

  End of Treatment at 12 months

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Patients with GCPC3 will receive daily Empagliflozin for 12 months.

Drug: Empagliflozin

Interventions

Empagliflozin DRUG

This is an open-label pilot study to evaluate the efficacy, safety, and tolerability of empagliflozin as a treatment for severe congenital neutropenia (SCN) in patients with glucose-6-phosphatase 3 (G6PC3) deficiency. Participants will be on a 12-month daily regimen of empagliflozin at a starting dose of 10 mg (phase A), which may be increased after 2 months to 25 mg (phase B). Evaluate the safety and efficacy of the biomarker response (the change in absolute neutrophil count \[ANC\] after one year of empagliflozin treatment relative to baseline ANC prior to drug treatment) in patients with G6PC3 deficiency.

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged \>=18 years.
• Documented SCN due to G6PC3 deficiency defined by genetic testing.
• History of ANC consistently \<1000 cells/microL when not treated with G-CSF.
• Current ANC\<1000 cells/microL when not treated with G-CSF.
• Participants must agree not to become pregnant for the duration of the study. Study participants must use 2 methods of birth control when engaging in sexual activities that can result in pregnancy, beginning 30 days before the first dose of empagliflozin through one month after treatment ends. One method must be a male or female condom. The other method may be any of the following:
• Hormonal contraception.
• Diaphragm or cervical cap with a spermicide.
• Intrauterine device.
• Able to provide informed consent.

You may not qualify if:

• Individuals meeting any of the following criteria will be excluded from study participation:
• Renal failure or eGFR\<45 mL/min/1.73 m\^2.
• Type 1 diabetes mellitus.
• Fasting hypoglycemia (\<60 mg/dL).
• Known hypersensitivity or allergy to any component of empagliflozin.
• Pregnant.
• Breastfeeding.
• Any condition that, in the opinion of the investigator, contraindicates participation in this study.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Banka S, Newman WG. A clinical and molecular review of ubiquitous glucose-6-phosphatase deficiency caused by G6PC3 mutations. Orphanet J Rare Dis. 2013 Jun 13;8:84. doi: 10.1186/1750-1172-8-84.

  PMID: 23758768 BACKGROUND

• Dale DC, Bolyard AA, Marrero T, Kelley ML, Makaryan V, Tran E, Leung J, Boxer LA, Kishnani PS, Austin S, Wanner C, Ferrecchia IA, Khalaf D, Maze D, Kurtzberg J, Zeidler C, Welte K, Weinstein DA. Neutropenia in glycogen storage disease Ib: outcomes for patients treated with granulocyte colony-stimulating factor. Curr Opin Hematol. 2019 Jan;26(1):16-21. doi: 10.1097/MOH.0000000000000474.

  PMID: 30451720 BACKGROUND

• Boztug K, Appaswamy G, Ashikov A, Schaffer AA, Salzer U, Diestelhorst J, Germeshausen M, Brandes G, Lee-Gossler J, Noyan F, Gatzke AK, Minkov M, Greil J, Kratz C, Petropoulou T, Pellier I, Bellanne-Chantelot C, Rezaei N, Monkemoller K, Irani-Hakimeh N, Bakker H, Gerardy-Schahn R, Zeidler C, Grimbacher B, Welte K, Klein C. A syndrome with congenital neutropenia and mutations in G6PC3. N Engl J Med. 2009 Jan 1;360(1):32-43. doi: 10.1056/NEJMoa0805051.

  PMID: 19118303 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Crohn Disease; Inflammatory Bowel Diseases

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• David H McDermott, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: October 15, 2021
• Study Start: November 16, 2021
• Primary Completion: May 2, 2025
• Study Completion: May 21, 2025
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)