Principal Investigator: Nicola Longo
Keywords: UX007 , triheptinoin , Fatty Acid Oxidation Department: Pediatric Genetics
IRB Number: 00082746
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics
Recruitment Status: Recruiting

Contact Information

Carrie Bailey

Brief Summary

This open-label long-term safety and efficacy study will provide an opportunity for LC-FAOD patients to be treated with UX007 for up to 7 years or until market approval under a single standardized protocol. The subjects may have participated in other studies or treatment programs with UX007/triheptanoin but would be consolidated into one program for long-term maintenance and consistent safety monitoring. The study is designed to obtain long-term safety information and evaluate maintenance of efficacy in a diverse LC-FAOD population.

The primary efficacy endpoint:
• The annualized LC-FAOD major events rate inclusive of skeletal myopathy
(rhabdomyolysis), hepatic (hypoglycemia) and cardiomyopathy events.

The secondary efficacy endpoints:

  • Energy metabolism in LC-FAOD on the basis of the following endpoints:
    • Ventricle size
    • Ejection fraction (EF)
    • Shortening fraction (SF)
  • Clinical events associated with LC-FAOD on the basis of the following endpoints
    • Annualized duration rate of all MCEs
    • Annualized event rate of rhabdomyolysis MCEs
    • Annualized duration rate of rhabdomyolysis MCEs
    • Annualized event rate of cardiomyopathy MCEs
    • Annualized duration rate of cardiomyopathy MCEs
    • Annualized event rate of hypoglycemic MCEs
    • Annualized duration rate of hypoglycemic MCEs

Exploratory endpoints include the following:

  • Functional disability and cognitive development (instrument selection based on age)
    • SF-10 physical health component summary (PCS) score
    • SF-10 mental health component summary (MCS) score
    • SF-12 physical health component summary (PCS) score
    • SF-12 mental health component summary (MCS) score
  • Clinical biomarkers endpoints:
    • Serum creatine kinase
    • Fasting serum glucose
    • Alanine aminotransferase (ALT)
    • Aspartate transaminase (AST)
    • Gamma glutamyl transpeptidase (GGT)
  • Growth measurements:
    • Height
    • Weight
    • Head circumference, if applicable (subjects ≤ 36 months of age)
      PK endpoints:
  • Plasma levels of UX007
  • Plasma levels of UX007 metabolites, including heptanoate, betahydroxypentanoate (BHP), and beta-hydroxybutyrate (BHB)

Safety endpoints:
Safety events will be collected as adverse events (AE) or serious adverse events (SAE).
The analyses of safety will include all subjects who receive at least one dose of study drug.
The safety endpoints in this study are:
• Incidence and severity of treatment emergent AEs (primary safety endpoint)
• Vital signs
• Incidence of laboratory abnormalities
• Concomitant medications

Inclusion Criteria

1. Male or female, 6 months of age or older
2. Prior participation in a clinical study assessing UX007/triheptanoin treatment for LC-FAOD. Study Sponsors/Collaborators include: Oregon Health & Science University, University of Pittsburgh, and Ultragenyx Pharmaceutical ( Identifiers: NCT01379625, NCT01461304, and NCT01886378). Patients who received UX007/triheptanoin treatment as part of other clinical studies; investigator sponsored trials (IST); expanded access/compassionate use treatment programs; or patients who are treatment naïve (i.e., naïve to both UX007 and food-grade triheptanoin), have failed conventional therapy and, in the opinion of the investigator and sponsor, have documented clear unmet need, may also be eligible at the discretion of the sponsor.
3. Confirmed diagnosis of LC-FAOD including: carnitine palmitoyltransferase (CPT I or CPT II) deficiency, very long chain acyl-CoA dehydrogenase (VLCAD) deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, trifunctional protein (TFP) deficiency, or carnitine-acylcarnitine translocase (CACT) deficiency. Information on diagnosis will be obtained from medical records and should include confirmed diagnosis by results of acylcarnitine profiles, fatty acid oxidation probe studies in cultured fibroblasts, and/or mutation analysis. 
4. Willing and able to complete all aspects of the study through the end of the study, including visits and tests, documentation of symptoms and diet, and administration of study medications. If a minor, have a caregiver(s) willing and able to assist in all applicable study requirements. 
5. Provide written informed consent (subjects aged ≥ 18 years), or provide written assent (where appropriate) and 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.
6. Females of child-bearing potential must have a negative urine pregnancy test at Baseline and be willing to have additional pregnancy tests during the study. Females considered not of child-bearing potential include those who have not experienced menarche, are post-menopausal (defined as having no menses for at least 12 months without an alternative medical cause), or are permanently sterile due to total hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.
7. Participants of child‐bearing potential or with partners of child-bearing potential who have not undergone a bilateral salpingo‐oophorectomy and are sexually active must consent to use a highly effective method of contraception as determined by the site investigator (i.e. oral hormonal contraceptives, patch hormonal contraceptives, vaginal ring, intrauterine device, physical 
double-barrier methods, surgical hysterectomy, vasectomy, tubal ligation or true abstinence [when this is in line with the preferred and usual lifestyle of the subject], which means not having sex because the subject chooses not to), from the period following the signing of the informed consent through 30 days after last dose of study drug.

Exclusion Criteria

1. Diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, short- or mediumchain FAOD, ketone body metabolism defect, propionic acidemia or methylmalonic acidemia
2. Patient qualifies for any other clinical trial designed to progressively evaluate the safety and efficacy of triheptanoin in LC-FAOD 
3. History of serious adverse reactions or known hypersensitivity to triheptanoin based on the judgement of the investigator and is determined to place the subject at increased risk for AE's
4. Pregnant and/or breastfeeding an infant at baseline or planning to become pregnant (self or partner) at any time during the study
5. 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 or unwilling to discontinue prohibited medications.