Repurposing Empagliflozin for DMD-associated Cardiomyopathy in Children 6-18 Years of Age

NCT06643442 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 24HL142024-000201-33
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims at exploring the use of empagliflozin in children and adolescents 6-18 years old with Duchenne muscular distrophy (DMD) - associated cardiomyopathy. This molecule is effective in reducing hospitalizations and mortality in adults with heart failure and is used in adolescents with type 2 diabetes mellitus, but little is known on children and adolescents with heart failure. Particularly, the best dose to use in this population is currently unknown. This trial aims to:

1. 1.define a dose rationale for this indication and age group (pharmacokinetic study),
2. 2.assess and monitor safety,
3. 3.assess ease-of-swallow,
4. 4.explore middle-term (3-6 months) efficacy and efficacy markers.

Conditions

DMD-associated Dilated Cardiomyopathy

Outcome Measures

Primary Outcomes (5)

• Pharmacokinetics - apparent clearance (CL/F)

  Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling \& simulation techniques). Basing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including CL/F).

  Visit 1 to Visit 3 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks after study start)

• Pharmacokinetics - apparent (central) volume of distribution (Vd/F)

  Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling \& simulation techniques). Basing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including Vd/F).

  Visit 1 to Visit 3 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks after study start)

• Pharmacokinetics - half-life

  Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling \& simulation techniques). Basing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including t1/2).

  Visit 1 to Visit 3 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks after study start)

• Pharmacokinetics - AUC

  Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling \& simulation techniques). Basing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including AUC).

  Visit 1 to Visit 3 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks after study start)

• Pharmacokinetics - maximal concentration (Cmax)

  Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling \& simulation techniques). Basing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including Cmax).

  Time Frame: Visit 1 to Visit 3 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks after study start)

Secondary Outcomes (16)

• Safety 1 - eGFR

  Visit 1 to Visit 5 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)

• Safety 2 - Occurrence of hypoglycemia

  Visit 1 to Visit 5 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)

• Safety 3 - Occurrence of ketoacidosis

  Visit 1 to Visit 5 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)

• Safety 4 - Occurrence of UTI

  Visit 1 to Visit 5 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)

• Ease of swallow

  Visit 1 (Visit 1 = day 1)

Other Outcomes (6)

• Efficacy markers (exploratory), Mechanistic insights - 1: body weight (kg)

  Visit 1 to Visit 5 (Visit 2 = 1 week, Visit 3 = 4-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months)

• Efficacy markers (exploratory), Mechanistic insights - 2: heart rate (bpm)

  Visit 1 to Visit 5 (Visit 2 = 1 week, Visit 3 = 4-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months)

• Efficacy markers (exploratory), Mechanistic insights - 3: blood pressure (SBP/DBP, mmHg)

  Visit 1 to Visit 5 (Visit 2 = 1 week, Visit 3 = 4-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months)

Study Arms (1)

Empagliflozin

EXPERIMENTAL

All participants will receive the IMP (open-label trial, primary outcome PK)

Drug: Empagliflozin Tablets

Interventions

Empagliflozin Tablets DRUG

Empagliflozin 10mg p.o. once daily (commercially available tablet)

Empagliflozin

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Currently on heart failure medication (any drug or any combination).
• Patients should potentially benefit from adding a SGLT2i (as judged by the treating physician and the PI or Co-PI).
• Patients need to be on stable medical treatment, defined as no new heart failure drug started over the preceding 2 weeks and no major drug dose modification (apart minor adaptations, like weight adaptations, rounding or formulation changes) during the 2 weeks prior to enrolment.
• Adolescents, respectively parents or caregivers of children, capable of giving informed consent.
• Ability to tolerate a cardiac MRI investigation without the need of general anaesthesia.

You may not qualify if:

• Inability to understand and go through the informed consent procedure.
• Inability to receive medications per os or through a nasogastric tube.
• Type 1 or Type 2 Diabetes mellitus or any underlying metabolic disease associated with hypoglycaemias.
• Body weight \<15kg.
• Current smokers (defined as \>1 cigarette/week).
• Use of any other nicotine-delivering product (e.g. nicotine patches).
• Any known illicit drug abuse.
• Active chronic HBV, HCV or HIV.
• Any major surgery within 4 weeks of first dose administration.
• Blood transfusion recipient within 4 weeks of dose administration.
• eGFR \<45mL/min/1.73m2 (simplified Schwartz formula or Filler formula).
• K+ \>6.5mmol/L.
• Blood glucose \<4mmol/L.
• Sustained or symptomatic arrhythmia insufficiently controlled with drug and/or device therapy.
• Cardio-surgical procedure within the 2 months prior to Visit 1, or interventional cardiac catheterization within 2 weeks prior to Visit 1, or the patient is planned to undergo cardiac surgery or an interventional cardiac catheterization during the study period (i.e. in the 6 months following Visit 1).

Sponsors & Collaborators

• Sebastiano Lava: lead
• Great Ormond Street Hospital for Children NHS Foundation Trust: collaborator
• University College, London: collaborator
• Centre Hospitalier Universitaire Vaudois: collaborator

Study Sites (1)

Great Ormond Street Hospital NHS Foundation Trust

London, Greater London, WC1N 3JH, United Kingdom

Location

Related Publications (18)

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• Das BB. Current State of Pediatric Heart Failure. Children (Basel). 2018 Jun 28;5(7):88. doi: 10.3390/children5070088.

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• Rossano JW, Kim JJ, Decker JA, Price JF, Zafar F, Graves DE, Morales DL, Heinle JS, Bozkurt B, Towbin JA, Denfield SW, Dreyer WJ, Jefferies JL. Prevalence, morbidity, and mortality of heart failure-related hospitalizations in children in the United States: a population-based study. J Card Fail. 2012 Jun;18(6):459-70. doi: 10.1016/j.cardfail.2012.03.001. Epub 2012 Apr 10.

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• Andrews RE, Fenton MJ, Dominguez T, Burch M; British Congenital Cardiac Association. Heart failure from heart muscle disease in childhood: a 5-10 year follow-up study in the UK and Ireland. ESC Heart Fail. 2016 Jun;3(2):107-114. doi: 10.1002/ehf2.12082. Epub 2016 Jan 24.

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• Towbin JA, Lowe AM, Colan SD, Sleeper LA, Orav EJ, Clunie S, Messere J, Cox GF, Lurie PR, Hsu D, Canter C, Wilkinson JD, Lipshultz SE. Incidence, causes, and outcomes of dilated cardiomyopathy in children. JAMA. 2006 Oct 18;296(15):1867-76. doi: 10.1001/jama.296.15.1867.

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MeSH Terms

Conditions

Dmd-Associated Dilated Cardiomyopathy

Interventions

empagliflozin

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Investigator

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: October 16, 2024
• Study Start: October 1, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: August 15, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)