Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) Extension Study for Subjects Previously Enrolled in Triheptanoin Studies

Phase 2

Completed

Conditions: Carnitine Palmitoyltransferase (CPT I or CPT II) Deficiency
Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency
Trifunctional Protein (TFP) Deficiency
Long-chain 3-hydroxy-acyl-CoA Dehydrogenase (LCHAD) Deficiency
Carnitine-acylcarnitine Translocase (CACT) Deficiency

Interventions: Drug: UX007

Registration Number: NCT02214160

Lead Sponsor: Ultragenyx Pharmaceutical Inc

Brief Summary: The primary objective of this study is to evaluate the long-term safety and efficacy of UX007 in participants with LC-FAOD. The secondary objectives of this study are to evaluate the effect of UX007 on energy metabolism in LC-FAOD and evaluate the impact of UX007 on clinical events associated with LC-FAOD.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 94

Inclusion Criteria

Male or female, 6 months of age or older
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 (ClinicalTrials.gov 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
Confirmed diagnosis of LC-FAOD including: CPT I or CPT II deficiency, VLCAD deficiency, LCHAD deficiency, TFP deficiency, or 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
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.
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
Participants of child-bearing potential or fertile males with partners of child-bearing potential who are sexually active must consent to use a highly effective method of contraception as determined by the Investigator from the period following the signing of the informed consent through 30 days after last dose of study drug

Exclusion Criteria

Diagnosis of medium-chain acyl coenzyme A dehydrogenase (MCAD) deficiency, short- or medium-chain FAOD, ketone body metabolism defect, propionic acidemia or methylmalonic acidemia
Patient qualifies for any other clinical trial designed to progressively evaluate the safety and efficacy of triheptanoin in LC-FAOD
Any known hypersensitivity to triheptanoin that, in the judgment of the Investigator, places the subject at increased risk for adverse effects
Pregnant and/or breastfeeding an infant at Screening or planning to become pregnant (self or partner) at any time during the study
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
UX007	UX007	Participants previously treated with UX007 or treatment-naive participants will begin or continue treatment with daily open-label UX007 while maintaining their other dietary restrictions.

Primary Outcome Measures

Name	Time	Method
Annualized LC-FAOD MCEs Rate: 18 Months Pre- and Entire UX007 Period Comparison for IST/Other Cohort and Triheptanoin-Naïve Cohort	Pre-UX007 treatment period (up to 18 months) and post-UX007 treatment period (up to 2072 days)	The annualized LC-FAOD MCE rate, inclusive of skeletal myopathy (rhabdomyolysis), hepatic (hypoglycemia) and cardiomyopathy events, defined as any visit to the emergency room (ER)/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25
Annualized LC-FAOD Major Clinical Events (MCEs) Rate: 18 Months Pre- and Entire UX007 Period Comparison for UX007-CL201-Rollover Cohort	Pre-UX007 treatment period (up to 18 months) and post-UX007 treatment period (up to 2072 days)	The annualized LC-FAOD MCE rate, inclusive of skeletal myopathy (rhabdomyolysis), hepatic (hypoglycemia) and cardiomyopathy events, defined as any visit to the emergency room (ER)/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs	Post-UX007 treatment through the end of treatment (up to 2072 days) plus 30-35 days	An adverse event (AE) was defined as any untoward medical occurrence, whether or not considered drug related. A serious adverse event (SAE) results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or disability; a congenital anomaly/birth defect; an important medical event. AEs were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (mild=1, moderate=2, severe=3, life-threatening=4, death=5).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF)	Baseline, Month 12, Month 24, Month 30, Month 36, Month 48, Month 60	Fractional shortening is calculated by measuring the percentage change in left ventricular diameter during systole. A negative value indicates less ventricular/muscular contractility, and a positive value indicates more ventricular/muscular contractility.
Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM)	Baseline, Month 12, Month 24, Month 36, Month 48, Month 60
Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants)	Baseline, Month 12, Month 24, Month 36, Month 48, Month 60	The Z-scores express the deviation (or how far away) the measure is from the mean LVSF based on the size or age of the pediatric participants: Z-score=0 indicates the participant is exactly the same as the mean of the healthy general population. Z-score=-1 indicates it's 1 standard deviation below the mean of the healthy population. Z-score=+1 indicates it's 1 standard deviation above the mean.
Annualized Duration Rate of Rhabdomyolysis MCEs	Post-UX007 treatment through the end of the study (up to 2072 days)	The annualized duration rate of LC-FAOD skeletal myopathy (rhabdomyolysis) MCEs, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized duration rate is calculated as the total duration (days) of events divided by the duration of data collection period in days/365.25.
Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD)	Baseline, Month 12, Month 24, Month 36, Month 48, Month 60
Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF)	Baseline, Month 12, Month 18, Month 24, Month 30, Month 36, Month 48, Month 60
Annualized Event Rate of Rhabdomyolysis MCEs	Post-UX007 treatment through the end of the study (up to 2072 days)	The annualized event rate of LC-FAOD major events of skeletal myopathy (rhabdomyolysis), defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25.
Annualized Event Rate of Cardiomyopathy MCEs	Post-UX007 treatment through the end of the study (up to 2072 days)	The annualized event rate of LC-FAOD major events inclusive of cardiomyopathy events, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25.
Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI)	Baseline, Month 12, Month 24, Month 36, Month 48, Month 60
Change From Baseline in ECHO Parameters Over Time: LVEF Z-Score (Pediatric Participants)	Baseline, Month 12, Month 24, Month 36	The Z-scores express the deviation (or how far away) the measure is from the mean LVEF based on the size or age of the pediatric participants: Z-score=0 indicates the participant is exactly the same as the mean of the healthy general population. Z-score=-1 indicates it's 1 standard deviation below the mean of the healthy population. Z-score=+1 indicates it's 1 standard deviation above the mean.
Annualized Duration Rate of Hypoglycemic MCEs	Post-UX007 treatment through the end of the study (up to 2072 days)	The annualized duration rate of LC-FAOD hepatic (hypoglycemia) MCEs, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized duration rate is calculated as the total duration (days) of events divided by the duration of data collection period in days/365.25.
Annualized Duration Rate of All MCEs	Post-UX007 treatment through the end of the study (up to 2072 days)	The annualized duration rate of LC-FAOD MCEs, inclusive of skeletal myopathy (rhabdomyolysis), hepatic (hypoglycemia) and cardiomyopathy events, and defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized duration rate is calculated as the total duration (days) of events divided by the duration of data collection period in days/365.25.
Annualized Duration Rate of Cardiomyopathy MCEs	Post-UX007 treatment through the end of the study (up to 2072 days)	The annualized duration rate of LC-FAOD cardiomyopathy MCEs, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized duration rate is calculated as the total duration (days) of events divided by the duration of data collection period in days/365.25
Annualized Event Rate of Hypoglycemic MCEs	Post-UX007 treatment through the end of the study (up to 2072 days)	The annualized event rate of LC-FAOD major events of hepatic (hypoglycemia) events, defined as any visit to the ER/acute care, hospitalization, emergency intervention (i.e. any unscheduled administration of therapeutics at home or in the clinic), or any similar event whether caused primarily by LC-FAOD or by an intercurrent illness complicated by LC-FAOD. The annualized event rate was calculated at the number of events divided by the duration of data collection period in days/365.25.

Trial Locations

Locations (11): Children's National Health System
🇺🇸
Washington, District of Columbia, United States
University of South Florida
🇺🇸
Tampa, Florida, United States
Vanderbilt Medical Center
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Nashville, Tennessee, United States
Seattle Children's Hospital
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Seattle, Washington, United States
University of California San Francisco
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San Francisco, California, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
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Chicago, Illinois, United States
Boston Children's Hospital
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Boston, Massachusetts, United States
Children's Hospital of Pittsburgh of UPMC
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Pittsburgh, Pennsylvania, United States
University of Utah
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Salt Lake City, Utah, United States
National Hospital for Neurology and Neurosurgery
🇬🇧
London, United Kingdom
Great Ormond Street Hospital
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London, United Kingdom