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

Ultragenyx Pharmaceutical Inc94 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

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

Interventions

UX007DRUG

Administered orally (PO) with food or by gastrostomy tube, at the target dose range of 25-35% of total calories.

Eligibility

Sex: ALLMin age: 6 Months

Medical Language ↔ Plain English

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 (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 3. 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 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 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: 1. Diagnosis of medium-chain acyl coenzyme A dehydrogenase (MCAD) deficiency, short- or medium-chain 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. Any known hypersensitivity to triheptanoin that, in the judgment of the Investigator, places the subject at increased risk for adverse effects 4. Pregnant and/or breastfeeding an infant at Screening 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

Locations (11)

University of California San Francisco

San Francisco, California, United States

Children's National Health System

Washington D.C., District of Columbia, United States

University of South Florida

Tampa, Florida, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Vanderbilt Medical Center

Nashville, Tennessee, United States

University of Utah

Salt Lake City, Utah, United States

Seattle Children's Hospital

Seattle, Washington, United States

National Hospital for Neurology and Neurosurgery

London, United Kingdom

...and 1 more locations

Outcomes

Primary Outcomes

Annualized LC-FAOD Major Clinical Events (MCEs) Rate: 18 Months Pre- and Entire UX007 Period Comparison for UX007-CL201-Rollover Cohort

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

Time frame: Pre-UX007 treatment period (up to 18 months) and post-UX007 treatment period (up to 2072 days)

Annualized LC-FAOD MCEs Rate: 18 Months Pre- and Entire UX007 Period Comparison for IST/Other Cohort and Triheptanoin-Naïve Cohort

Time frame: Pre-UX007 treatment period (up to 18 months) and post-UX007 treatment period (up to 2072 days)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs

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).

Time frame: Post-UX007 treatment through the end of treatment (up to 2072 days) plus 30-35 days

Secondary Outcomes

Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI)

Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60

Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM)

Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60

Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD)

Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60

Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF)

Time frame: Baseline, Month 12, Month 18, Month 24, Month 30, Month 36, Month 48, Month 60

Change From Baseline in ECHO Parameters Over Time: LVEF Z-Score (Pediatric Participants)

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.

Time frame: Baseline, Month 12, Month 24, Month 36

Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF)

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.

Time frame: Baseline, Month 12, Month 24, Month 30, Month 36, Month 48, Month 60

Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants)

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.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60

Annualized Duration Rate of All MCEs

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.