Clinical trial NCT02214160: Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) Extension Study for Subjects Previously Enrolled in Triheptanoin Studies
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Ultragenyx Pharmaceutical Inc
Sponsor class: INDUSTRY
First posted: 2014-08-12
Enrollment: 94
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Annualized LC-FAOD Major Clinical Events (MCEs) Rate: 18 Months Pre- and Entire UX007 Period Comparison for UX007-CL201-Rollover Cohort
timeFrame: Pre-UX007 treatment period (up to 18 months) and post-UX007 treatment period (up to 2072 days)
measure: Annualized LC-FAOD MCEs Rate: 18 Months Pre- and Entire UX007 Period Comparison for IST/Other Cohort and Triheptanoin-Naïve Cohort
timeFrame: Pre-UX007 treatment period (up to 18 months) and post-UX007 treatment period (up to 2072 days)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs
timeFrame: Post-UX007 treatment through the end of treatment (up to 2072 days) plus 30-35 days
Secondary outcomes:
measure: Change From Baseline in Echocardiogram (ECHO) Parameters Over Time: Left Ventricular Mass Index (LVMI)
timeFrame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60
measure: Change From Baseline in ECHO Parameters Over Time: Left Ventricular Mass (LVM)
timeFrame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60
measure: Change From Baseline in ECHO Parameters Over Time: Left Ventricular Diameter (LVD)
timeFrame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60
measure: Change From Baseline in ECHO Parameters Over Time: Left Ventricular Ejection Fraction (LVEF)
timeFrame: Baseline, Month 12, Month 18, Month 24, Month 30, Month 36, Month 48, Month 60
measure: Change From Baseline in ECHO Parameters Over Time: LVEF Z-Score (Pediatric Participants)
timeFrame: Baseline, Month 12, Month 24, Month 36
measure: Change From Baseline in ECHO Parameters Over Time: Left Ventricular Shortening Fraction (LVSF)
timeFrame: Baseline, Month 12, Month 24, Month 30, Month 36, Month 48, Month 60
measure: Change From Baseline in ECHO Parameters Over Time: LVSF Z-Score (Pediatric Participants)
timeFrame: Baseline, Month 12, Month 24, Month 36, Month 48, Month 60
measure: Annualized Duration Rate of All MCEs
timeFrame: Post-UX007 treatment through the end of the study (up to 2072 days)
measure: Annualized Event Rate of Rhabdomyolysis MCEs
timeFrame: Post-UX007 treatment through the end of the study (up to 2072 days)
measure: Annualized Duration Rate of Rhabdomyolysis MCEs
timeFrame: Post-UX007 treatment through the end of the study (up to 2072 days)
measure: Annualized Event Rate of Cardiomyopathy MCEs
timeFrame: Post-UX007 treatment through the end of the study (up to 2072 days)
measure: Annualized Duration Rate of Cardiomyopathy MCEs
timeFrame: Post-UX007 treatment through the end of the study (up to 2072 days)
measure: Annualized Event Rate of Hypoglycemic MCEs
timeFrame: Post-UX007 treatment through the end of the study (up to 2072 days)
measure: Annualized Duration Rate of Hypoglycemic MCEs
timeFrame: Post-UX007 treatment through the end of the study (up to 2072 days)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Washington
country: United States
facility: Children's National Health System
state: District of Columbia
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: London
country: United Kingdom
facility: National Hospital for Neurology and Neurosurgery
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
Study officials:
affiliation: Ultragenyx Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.