A Study to Determine the Effect of Triheptanoin Compared With Even-Chain MCT on MCEs in Pediatric Patients With LC-FAOD

A Randomized, Double-blind, Multicenter Study to Determine the Effect of Triheptanoin Compared With Even-chain, Medium-chain Triglycerides (MCT) on Major Clinical Events (MCEs) in Pediatric Patients With Long-chain Fatty Acid Oxidation Disorders (LC-FAOD)

The main goal of this study is to evaluate the effects of triheptanoin versus Medium-chain Triglycerides (MCT) on frequency of Major Clinical Events (MCEs).

Study Overview

• Status: Active, not recruiting
• Conditions: Long-chain Fatty Acid Oxidation Disorders (LC-FAOD)
• Intervention / Treatment: Drug: Triheptanoin; Dietary supplement: MCT Oil

Detailed Description

Participants will be randomly assigned 1:1 to receive triheptanoin or MCT oil. The duration of the study is estimated to be 3.5 to 4 years. The study comprises the following: Screening Period, Baseline (Month 0), Double-blind Treatment Period (including Titration and End of Study Visit), Safety Follow-up Phone Visit, and an Open Access Period.

In addition, a substudy will examine the effect of triheptanoin versus MCT on decreasing liver fat fraction to avoid or improve steatosis in subjects with LC-FAOD. Participants older than 2 years of age at selected sites will be invited to screen for the Liver Substudy.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia, 120-08
    • General University Hospital in Prague-GUH (Všeobecná fakultní nemocnice v Praze- VFN)
• Germany
  • Freiburg im Breisgau, Germany, 79106
    • Universitätsklinikum Freiburg
• Japan
  • Tokyo
    • Bunkyo City, Tokyo, Japan, 113-8431
      • Juntendo University Hospital
    • Minato, Tokyo, Japan
      • The Jikei University Hospital
• Poland
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 04-730
      • Instytut Pomnik-Centrum Zdrowia Dziecka
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-952
      • Gdańksi Uniwersytet Medyczny
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11211
    • King Faisal Specialist Hospital & Research Centre
• Spain
  • A Coruña, Spain, 15706
    • University Hospital Santiago de Compostela
  • Madrid, Spain, 28041
    • University Hospital 12 de Octubre
  • Esplugues de Llobregat
    • Barcelona, Esplugues de Llobregat, Spain, 08950
      • Sant Joan de Deu Hospital (SJD)
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye)
    • Çukurova University
  • Ankara, Turkey (Türkiye)
    • Gazi University
  • Bornova-İzmir, Turkey (Türkiye)
    • Ege University
  • Istanbul, Turkey (Türkiye), 34093
    • Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi
  • Istanbul, Turkey (Türkiye), 34116
    • Cerrahpasa Medical Faculty

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for Main Study:

• Males and females, from 0 (including newborns) to < 18 years of age at time of randomization
• Confirmed diagnosis of LC-FAOD
• Have a caregiver(s) willing and able to assist in all applicable study requirements
• Have a legally authorized representative willing and able to provide written informed consent after the nature of the study has been explained and prior to any research-related procedures, and the study participant to be able to provide age-appropriate written assent

• Have ANY ONE of the following significant clinical manifestations of LC-FAOD:

  • At least 2 in the prior year, or 3 in the prior 2 years, of severe major episodes of metabolic decompensation (eg, hypoglycemia, rhabdomyolysis, or exacerbation of cardiomyopathy, requiring ER/urgent care unit visits or hospitalizations)
  • Recurrent symptomatic hypoglycemia (clinical symptoms of hypoglycemia) requiring intervention
  • Susceptibility to hypoglycemia after short periods of fasting (less than 4 to 12 hours, depending on age)
  • Evidence of functional cardiomyopathy requiring ongoing medical management or clinical manifestation of heart failure
  • Sibling(s) with the same pathogenic variant who presented with MCEs
  • Participant with pathogenic variants that are known or suspected to be associated with absent or severely reduced enzyme activity or with severe disease manifestations.
• From the period following informed consent to 5 days after the last dose of study drug, females of childbearing potential and fertile males must consent to use highly effective contraception. If female, agree not to become pregnant. If male, agree not to father a child or donate sperm

Inclusion Criteria for Liver Substudy:

• Enrollment in the Main Study of Study UX007-CL302
• Age > 2 years
• Liver fat content ≥ 2% and < 20% PDFF as assessed by 1 H-MRS
• Body mass index < 95th percentile
• Able to comply with instructions (remaining still during scan) and requirements (eg, constraints on recent meals, no metallic items or implanted devices in the body, no recent contrast agents) for liver 1 H-MRS scan

Exclusion Criteria for Main Study:

• Enrolled in a clinical study involving concurrent use of an investigational drug product within 30 days before Screening
• Use of a prohibited medication (eg, valproate products or pancreatic lipase inhibitors) within 30 days before Screening, or unwilling to avoid a prohibited medication or other substance that may confound study objectives
• Treatment with triheptanoin within 60 days of Screening
• History of known hypersensitivity to triheptanoin or MCT or its excipients that, in the judgement of the Investigator, places the subject at increased risk for adverse effects
• Caregiver unwilling or unable to sign informed consent, or release of medical records, or follow study procedures
• Have any comorbid conditions, including unstable major organ-system disease(s), that in the opinion of the Investigator places the subject at increased risk of complications, interferes with study participation or compliance, or confounds study objectives or interpretation of results. History of metabolic decompensation(s) with metabolic acidosis, hyperammonemia, and/or liver enzyme elevations does not constitute an exclusion criterion unless in the opinion of the Investigator places the subject at increased risk of complications, interferes with study participation or compliance, or confounds study objectives or interpretation of results.
• Have a diagnosis of pancreatic insufficiency
• Pregnant, breastfeeding, or planning to become pregnant (self or partner) at any time during the study

Exclusion Criteria for Liver Substudy:

• Acute or chronic liver disease other than LC-FAOD that presents with increased risk of liver fat (eg, hepatic cirrhosis, viral toxic or drug hepatitis, diabetes mellitus) and/or metabolic syndrome
• Need for anesthesia/sedation to perform liver 1 H-MRS

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Triheptanoin; Participants will be given prescriptions for triheptanoin in mL/day, which will be divided into approximately 4 administrations per day, with precise instructions for administration. Triheptanoin will be titrated up to the first 6 weeks of the study. After titration, the dose is to remain stable for the remainder of the Double-blind Treatment Period. Following the Double-blind Treatment Period, open-label triheptanoin will be provided at participants' current dose during an Open Access Period, if no other options to receive trihepatnoin are available locally.	Drug: Triheptanoin; Liquid for oral (PO) or enteral feeding tube administration; Other Names: UX007; Dojolvi
Active Comparator: MCT; Participants will be given prescriptions for MCT in mL/day, which will be divided into approximately 4 administrations per day, with precise instructions for administration. MCT will be titrated up to the first 6 weeks of the study. After titration, the dose is to remain stable for the remainder of the Double-blind Treatment Period. Following the Double-blind Treatment Period, open-label triheptanoin will be provided at participants' current dose during an Open Access Period, if no other options to receive trihepatnoin are available locally.	Dietary supplement: MCT Oil; Liquid for oral (PO) or enteral feeding tube administration; Other Names: Medium-chain Triglyceride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Annualized Event Rate of Major Clinical Events (MCEs)	Up to Year 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Left Ventricular Ejection Fraction	Baseline, Up to Year 1
Change From Baseline in Left Ventricular Systolic Volume	Baseline, Up to Year 1
Change From Baseline in Left Ventricular Wall Mass	Baseline, Up to Year 1
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs)	Up to Year 4
Number of Participants With TEAEs and Serious TEAEs Leading to Dose Modifications, Dose Reductions, Treatment Interruptions, Discontinuations From Study Drug, and Discontinuations From the Study	Up to Year 4
Plasma Concentration Levels of Heptanoate	Up to Year 1
Plasma Concentration Levels of Beta Hydroxypentanoate (BHP)	Up to Year 1
Acceptability and Palatability Survey Scores of Triheptanoin Mixed with Oral Liquids	Up to Year 1
Liver Substudy (Single Study Site Only): Change from Baseline to 6 Months in Hepatic Proton Density Fat Fraction (PDFF%), Assessed by 1H-Magnetic Resonance Spectroscopy (1H-MRS)	Baseline, Month 6
Annualized Duration of MCEs	Up to Year 4
Annualized Hypoglycemic Event-rate Captured as MCEs and At-home Clinical Events (HCEs)	Up to Year 4
Clinical Global Impression of Change [CGI-C] Scale Score	Up to Year 4
Annualized Frequency of Rhabdomyolysis-MCEs and Cardiomyopathy-MCEs	Up to Year 4
Annualized Duration of Rhabdomyolysis-MCEs, Cardiomyopathy-MCEs, and Hypoglycemic-MCEs	Up to Year 4
Change From Baseline in Caregiver-reported Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scale Score for Participants 2 Years of Age or Older	Up to Year 4
Change From Baseline in PedsQL Infant Scale Score for Participants Ages 1 to <24 Months	Up to Year 4
Survival Time	Up to Year 4
Annualized Hospitalization Days	Up to Year 4
Number of Missed School or Learning Opportunity Days	Up to Year 4

Collaborators and Investigators

• Sponsor: Ultragenyx Pharmaceutical Inc
• Investigators: Study Director: Medical Director, Ultragenyx Pharmaceutical Inc

Publications and helpful links

Helpful Links

• Ultragenyx Patient Advocacy/LC-FAOD Disease Information
• Ultragenyx Transparency Commitment

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2023
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: June 27, 2023
• First Submitted That Met QC Criteria: June 27, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Carnitine Palmitoyl Transferase (CPT) I Deficiency; Carnitine Palmitoyl Transferase (CPT) II Deficiency; Carnitine/acylcarnitine Translocase (CACT) Deficiency; Very Long Chain Acyl-coenzyme A Dehydrogenase (VLCAD) Deficiency; Long-chain 3-hydroxyacyl-coenzyme A Dehydrogenase (LCHAD) Deficiency; Mitochondrial Trifunctional Protein (TFP) Deficiency
• Additional Relevant MeSH Terms: VLCAD deficiency; triheptanoin
• Other Study ID Numbers: UX007-CL302; 2022-001539-10 (EudraCT Number); 2023-509809-76-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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