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

Long-chain Fatty Acid Oxidation Disorders (LC-FAOD) Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05933200
• Other study ID #: UX007-CL302
• Secondary ID: 2022-001539-10
• Status: Recruiting
• Phase: Phase 3
• Start date: February 28, 2023
• Est. completion date: September 2026

Study information

• Verified date: May 2024
• Source: Ultragenyx Pharmaceutical Inc
• Contact: Patients Contact: Trial Recruitment
• Phone: (+1) 888-756-8657
• Email: trialrecruitment[@]ultragenyx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

Participants will be randomly assigned 1:1 to receive triheptanoin or MCT oil. The duration of the study, which is estimated to be 3.5 to 4 years and comprises of the following: Screening Period, Baseline (Month 0), Double-blind Treatment Period (including Titration and End of Study Visit), and Safety Follow-up Phone Visit. In addition, a substudy will examine the effect of triheptanoin versus MCT on decreasing hepatic lipid content 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 2026
• Est. primary completion date: September 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

Inclusion Criteria for Main Study:

• Males and females, from 0 (including newborns) to < 18 years of age
• 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 time of informed consent to 5 days after the last dose of study drug in this study, females of childbearing potential and fertile males must consent to use highly effective methods of contraception. If female, agree not to become pregnant. If male, agree not 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
• Caregiver unwilling or unable to sign informed consent, or release of medical records, or follow study procedures
• Have any co-morbid 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. 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
• 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

Related Conditions & MeSH terms

• Long-chain Fatty Acid Oxidation Disorders (LC-FAOD)

Intervention

Drug:
• Triheptanoin
Liquid for oral (PO) or enteral feeding tube administration

Dietary Supplement:
• MCT Oil
Liquid for oral (PO) or enteral feeding tube administration

Locations

Country	Name	City	State
Czechia	General University Hospital in Prague-GUH (Všeobecná fakultní nemocnice v Praze- VFN)	Prague
Germany	Universität Freiburg	Freiburg im Breisgau
Poland	Gdanksi Uniwersytet Medyczny	Gdansk	Pomorskie
Poland	Poznan University of Medical Sciences	Poznan
Poland	Instytut Pomnik-Centrum Zdrowia Dziecka	Warszawa	Mazowieckie
Saudi Arabia	King Faisal Specialist Hospital & Research Centre	Riyadh
Spain	University Hospital Santiago de Compostela	A Coruña
Spain	Sant Joan de Deu Hospital (SJD)	Barcelona	Esplugues De Llobregat
Spain	University Hospital 12 de Octubre	Madrid
Turkey	Cukurova University	Adana
Turkey	Gazi University	Ankara
Turkey	Ege University	Bornova-Izmir
Turkey	Cerrahpasa Medical Faculty	Istanbul
Turkey	Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi	Istanbul
United Kingdom	Great Ormond Street Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Ultragenyx Pharmaceutical Inc

Countries where clinical trial is conducted

Czechia,  Germany,  Poland,  Saudi Arabia,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Event Rate of Major Clinical Events (MCEs) During the Double-blind Treatment Period		Up to Year 4
Secondary	Annualized Duration of MCEs During the Double-blind Treatment Period		Up to Year 4
Secondary	Annualized Hypoglycemic Event-rate Captured as MCEs and/or At-home Clinical Events (HCEs) During the Double-blind Treatment Period		Up to Year 4
Secondary	Clinician-reported Change in Global Impression of Disease Severity (Clinical Global Impression of Change [CGI-C] Scale) Score at End of Study (EOS)		Up to Year 4
Secondary	Change From Baseline in Left Ventricular Ejection Fraction		Baseline, Up to Year 1
Secondary	Change From Baseline in Left Ventricular Systolic Volume		Baseline, Up to Year 1
Secondary	Change From Baseline in Left Ventricular Wall Mass		Baseline, Up to Year 1
Secondary	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
Secondary	Liver Substudy (Single Study Site Only): Change From Baseline to 6 Months in Creatine Kinase/Alanine Aminotransferase (CK/ALT)		Baseline, Month 6
Secondary	Liver Substudy (Single Study Site Only): Change From Baseline to 6 Months in Alanine Aminotransferase (ALT)		Baseline, Month 6
Secondary	Liver Substudy (Single Study Site Only): Change From Baseline to 6 Months in Aspartate Aminotransferase (AST)		Baseline, Month 6
Secondary	Annualized Frequency of Rhabdomyolysis and Cardiomyopathy-MCEs During the Double-blind Treatment Period		Up to Year 4
Secondary	Annualized Duration of Rhabdomyolysis, Cardiomyopathy, and Hypoglycemic-MCEs During the Double-blind Treatment Period		Up to Year 4
Secondary	Change From Baseline to EOS 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
Secondary	Change From Baseline to EOS in PedsQL Infant Scale Score for Participants Ages 1 to <24 Months		Up to Year 4
Secondary	Survival Time During the Double-blind Treatment Period		Up to Year 4
Secondary	Annualized Hospitalization Days During the Double-blind Treatment Period		Up to Year 4
Secondary	Number of Missed School or Learning Opportunity Days During the Double-blind Treatment Period		Up to Year 4
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs)		Up to Year 4
Secondary	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
Secondary	Plasma Concentration Levels of Heptanoate		Up to Year 1
Secondary	Plasma Concentration Levels of Beta Hydroxypentanoate (BHP)		Up to Year 1
Secondary	Acceptability and Palatability Survey Scores of Triheptanoin Mixed with Oral Liquids		Up to Year 1

External Links

•   Ultragenyx Patient Advocacy/LC-FAOD Disease Information