Long-chain Fatty Acid Oxidation Disorders (LC-FAOD)
Conditions
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
Brief 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).
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.
Interventions
DRUGTriheptanoin
Liquid for oral (PO) or enteral feeding tube administration
DIETARY_SUPPLEMENTMCT Oil
Liquid for oral (PO) or enteral feeding tube administration
Sponsors
Ultragenyx Pharmaceutical Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Annualized Event Rate of Major Clinical Events (MCEs) | Up to Year 4 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 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 |
| 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 |
Countries
Czechia, Germany, Japan, Poland, Saudi Arabia, Spain, Turkey (Türkiye)
Contacts
STUDY_DIRECTORMedical Director
Ultragenyx Pharmaceutical Inc
Outcome results
None listed