A Study of UX007 (Triheptanoin) in Participants With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)

An Open-label Phase 2 Study to Assess Safety and Clinical Effects of UX007 in Subjects With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)

The primary objective of the study was to evaluate the impact of UX007 on acute clinical pathophysiology associated with LC-FAOD following 24 weeks of treatment.

Inclusion Criteria:

• Confirmed diagnosis of CPT II, VLCAD, LCHAD, or TFP deficiency, based on results of acylcarnitine profiles, fatty acid oxidation probe studies in cultured fibroblasts, and/or mutation analysis obtained from medical records.

• Male or female, at least 6 months of age

• Willing and able to complete all aspects of the study through the end of the study. If a minor, have a caregiver(s) willing and able to assist in all applicable study requirements.

• 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

• Willing and able to provide access to medical records charting the last 18-24 months of care prior to the study initiation, or from birth for those subjects less than 18 months of age

• No history of serious adverse reactions or known hypersensitivity to triheptanoin

• Currently managed on a stable treatment regimen (including diet), which may include low-fat/high-carbohydrate diet, avoidance of fasting, carnitine and/or medium-chain triglyceride (MCT) oil. The treatment regimen (including diet) should be stable for the last 60 days to assure that changes in the subject's condition are not confounded by recent changes in the treatment regimen that could affect the 4 week run-in evaluation period. Once study drug treatment has started, must be willing to maintain all aspects of the subject's treatment regimen and diet unchanged, other than discontinuation of MCT oil, in order to avoid potential variability of response due to variations in dietary intake.

• Have severe LC-FAOD, as evidenced by ANY ONE of the following significant clinical manifestations despite therapy:

  • Chronic Elevated Creatine Kinase (CK) with Major Clinical Events: Elevated mean CK levels over the last 6 months -1 year (defined as ≥ 2X upper limit of age/gender-matched normal, or ≥ 500 units/L if age-matched reference not established) not associated with an acute rhabdomyolysis event, AND at least two major clinical events (as defined in the protocol) in the last year, or at least four major clinical events over the last two years,
  • Episodic Elevated CK with Reported Muscle Dysfunction: Episodes of elevated CK levels over the last 6 months -1 year (defined as ≥ 2X upper limit of age/gender-matched normal, or ≥ 500 units/L if age-matched reference is not established) not associated with an acute rhabdomyolysis event, AND patient report of frequent muscle fatigue, exercise intolerance, or limitation of exercise,
  • Highly Elevated CK but Asymptomatic: More seriously elevated mean CK levels (defined as ≥ 4X upper limit of age/gender-matched normal, or ≥ 1000 units/L if age-matched reference is not established) consistent with substantial chronic muscle rupture over the last 6 months-1 year, regardless of frequency of hospitalizations or ER events,
  • Frequent Severe Major Medical Episodes (at least 3 within the past year, or 5 within 2 years) of hypoglycemia, rhabdomyolysis, or exacerbation of cardiomyopathy [CM], requiring emergency room [ER]/acute care visits or hospitalizations,
  • Severe Susceptibility to Hypoglycemia (serum glucose <60 mg/dL) after short periods of fasting (less than 4-12 hours, depending on age), with at least 2 events in the last year that require ongoing prophylactic management, OR recurrent symptomatic hypoglycemia (blood glucose levels or clinical symptoms of hypoglycemia) at home requiring intervention ≥ 2 times per week,
  • Evidence of Functional Cardiomyopathy (with echocardiogram (ECHO) within past 90 days documenting poor ejection fraction [EF]) requiring ongoing medical management

• Females who have reached menarche must have a negative pregnancy test at Screening. If sexually active, subject must be willing to use acceptable method of contraception and have additional pregnancy tests during the study.

Exclusion Criteria:

• Diagnosis of carnitine-acylcarnitine translocase (CACT) or CPT I
• Diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, short- or medium-chain FAOD, ketone body metabolism defect, propionic acidemia or methylmalonic acidemia
• Enrolled in a clinical study involving concurrent use of an investigational drug product within the last 30 days, or unwilling to discontinue use of a prohibited medication or other substance that may confound study objectives
• Unwilling to sign informed consent or release of medical records
• 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