A Study of UX007 (Triheptanoin) in Participants With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)
Condition: Long-chain Fatty Acid Oxidation Disorders (LC-FAOD); Carnitine Palmitoyltransferase (CPT II) Deficiency; Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency; Longchain 3-hydroxy-acyl-CoA Dehydrogenase (LCHAD) Deficiency; Trifunctional Protein (TFP) Deficiency
Intervention: UX007
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 6 Months
Healthy volunteers: No
Keywords: FAOD; VLCAD; CPT II; CPT2; CPT 2; LCHAD; UX007; Triheptanoin; TFP; C7

Summary:

      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.
    

Eligibility criteria:

        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