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

July 28, 2023 updated by: Ultragenyx Pharmaceutical Inc

An Open-label Long-Term Safety and Efficacy Extension Study in Subjects With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) Previously Enrolled in UX007 or Triheptanoin Studies

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

94

Phase

  • Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, WC1N 3JH
        • Great Ormond Street Hospital
      • London, United Kingdom, WC1N 3BP
        • National Hospital For Neurology and Neurosurgery
  • United States
    • California
      • San Francisco, California, United States, 94143
        • University of California San Francisco
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Health System
    • Florida
      • Tampa, Florida, United States, 33606
        • University of South Florida
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Ann & Robert H. Lurie Children's Hospital of Chicago
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Medical Center
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • University of Utah
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 months and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: UX007
Administered orally (PO) with food or by gastrostomy tube, at the target dose range of 25-35% of total calories.
Other Names:
  • C7
  • Triheptanoin

What is the study measuring?

Primary Outcome Measures

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

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
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
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
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)
Time Frame: 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.
Baseline, Month 12, Month 24, Month 36
Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF)
Time Frame: 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.
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)
Time Frame: 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.
Baseline, Month 12, Month 24, Month 36, Month 48, Month 60
Annualized Duration Rate of All MCEs
Time Frame: 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.
Post-UX007 treatment through the end of the study (up to 2072 days)
Annualized Event Rate of Rhabdomyolysis MCEs
Time Frame: 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.
Post-UX007 treatment through the end of the study (up to 2072 days)
Annualized Duration Rate of Rhabdomyolysis MCEs
Time Frame: 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.
Post-UX007 treatment through the end of the study (up to 2072 days)
Annualized Event Rate of Cardiomyopathy MCEs
Time Frame: 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.
Post-UX007 treatment through the end of the study (up to 2072 days)
Annualized Duration Rate of Cardiomyopathy MCEs
Time Frame: 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
Post-UX007 treatment through the end of the study (up to 2072 days)
Annualized Event Rate of Hypoglycemic MCEs
Time Frame: 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.
Post-UX007 treatment through the end of the study (up to 2072 days)
Annualized Duration Rate of Hypoglycemic MCEs
Time Frame: 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.
Post-UX007 treatment through the end of the study (up to 2072 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ultragenyx Pharmaceutical Inc

Investigators

  • Study Director: Medical Director, Ultragenyx Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 9, 2014

Primary Completion (Actual)

December 3, 2020

Study Completion (Actual)

December 3, 2020

Study Registration Dates

First Submitted

August 6, 2014

First Submitted That Met QC Criteria

August 7, 2014

First Posted (Estimated)

August 12, 2014

Study Record Updates

Last Update Posted (Actual)

August 1, 2023

Last Update Submitted That Met QC Criteria

July 28, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • UX007-CL202
  • 2016-000322-19 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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