Status: Not yet recruiting
Keywords: LCHAD , VLCAD , CPT 2 deficiency
IRB Number: 00068585
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics

Brief Summary

The primary objective of the study is to:
Evaluate the impact of UX007 on acute clinical pathophysiology associated with long chain fatty acid oxidation disorders following 24 weeks of treatment 
The secondary objectives of the study are to:
• Evaluate the safety of UX007 treatment in subjects with long chain fatty acid oxidation disorders
• Evaluate the effect of UX007 on energy metabolism in long chain fatty acid oxidation disorders
The objective of the Extension Period of the study is to:
• Evaluate the impact of UX007 on major clinical events associated with long chain fatty acid oxidation disorders (following 78
weeks treatment)

Study Purpose:

This open-label study will enroll  subjects with long chain fatty acid oxidation disorders who continue to suffer the effects of fatty acid oxidation disorders disease despite current therapy. Following completion of a run-in period to evaluate clinical baseline on current standard of care, the study will assess the safety and efficacy of UX007 treatment.

Principal Investigator: Nicola Longo
Department: Pediatric Genetics
Co Investigator: Lorenzo Botto

Contact Information

Name:Carrie Bailey
Phone: 8015873605
Email: carrie.bailey@hsc.utah.edu

Inclusion Criteria

• Confirmed diagnosis of one of the four most common LC-FAOD disorders: carnitine palmitoyltransferase (CPT II) deficiency, very long chain acyl-CoA dehydrogenase (VLCAD) deficiency, long chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiency, and trifunctional protein (TFP) deficiency. Diagnosis must be confirmed by 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, 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.
• 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
• 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 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 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), 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 CM, requiring 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 CM: (with echocardiogram (ECHO) within past 90 days documenting  poor 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) deficiency, 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