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

NCT02214160 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: UX007-CL2022016-000322-19
• Study Type: interventional
• Target: 94
• Locations: 2 countries
• Sites: 11

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.

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; Carnitine-acylcarnitine Translocase (CACT) Deficiency

Keywords

Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD); 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; carnitine-acylcarnitine translocase (CACT) deficiency; Triheptanoin; UX007; C7

Outcome Measures

Primary Outcomes (3)

• 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

  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

  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

  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 Outcomes (14)

• 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: Left Ventricular Mass (LVM)

  Baseline, Month 12, Month 24, Month 36, Month 48, Month 60

• 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

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

  Baseline, Month 12, Month 24, Month 36

Study Arms (1)

UX007

EXPERIMENTAL

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

Interventions

UX007 DRUG

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

Also known as: Triheptanoin, C7

UX007

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (11)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Children's National Health System

Washington D.C., District of Columbia, 20010, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

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

Chicago, Illinois, 60611, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Vanderbilt Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

National Hospital for Neurology and Neurosurgery

London, WC1N 3BP, United Kingdom

Location

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

Location

Related Publications (2)

• Vockley J, Burton B, Berry G, Longo N, Phillips J, Sanchez-Valle A, Chapman K, Tanpaiboon P, Grunewald S, Murphy E, Lu X, Cataldo J. Effects of triheptanoin (UX007) in patients with long-chain fatty acid oxidation disorders: Results from an open-label, long-term extension study. J Inherit Metab Dis. 2021 Jan;44(1):253-263. doi: 10.1002/jimd.12313. Epub 2020 Sep 14.

  PMID: 32885845 BACKGROUND

• Vockley J, Burton BK, Berry G, Longo N, Phillips J, Sanchez-Valle A, Chapman KA, Tanpaiboon P, Grunewald S, Murphy E, Lu X, Rahman S, Ray K, Reineking B, Pisani L, Ramirez AN. Triheptanoin for the treatment of long-chain fatty acid oxidation disorders: Final results of an open-label, long-term extension study. J Inherit Metab Dis. 2023 Sep;46(5):943-955. doi: 10.1002/jimd.12640. Epub 2023 Jun 19.

  PMID: 37276053 BACKGROUND

MeSH Terms

Conditions

VLCAD deficiency

Interventions

triheptanoin

Results Point of Contact

• Title: Medical Information
• Organization: Ultragenyx Pharmaceutical Inc

medinfo@ultragenyx.com

1-888-756-8657

Study Officials

• Medical Director

  Ultragenyx Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: August 6, 2014
• First Posted: August 12, 2014
• Study Start: December 9, 2014
• Primary Completion: December 3, 2020
• Study Completion: December 3, 2020
• Last Updated: August 1, 2023
• Results First Posted: December 8, 2021

Record last verified: 2023-07

Locations

GB (2); US (9)