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NCT01886378

A Study of UX007 (Triheptanoin) in Participants With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)

Completed Phase 2 Results posted Last updated 11 February 2021
What this trial tests

Phase 2 trial testing UX007 in Long-chain Fatty Acid Oxidation Disorders (LC-FAOD) in 29 participants. Completed in 25 August 2016.

Timeline
6 February 2014
Primary endpoint
25 August 2016
25 August 2016

Quick facts

Lead sponsorUltragenyx Pharmaceutical Inc
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment29
Start date6 February 2014
Primary completion25 August 2016
Estimated completion25 August 2016
Sites10 locations across United Kingdom, United States

Drugs / interventions tested

Conditions studied

Sponsor

Ultragenyx Pharmaceutical Inc — full company profile →

Who can join

6 Months and older, any sex, with Long-chain Fatty Acid Oxidation Disorders (LC-FAOD) or Carnitine Palmitoyltransferase (CPT II) Deficiency. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Time Adjusted-Area Under the Curve (AUC/Time) for Workload During Cycle Ergometry at Week 24 Primary · Baseline, Week 24

To evaluate the impact 24 weeks of treatment with UX007 has on exercise intolerance, the change from Baseline in time adjusted-AUC (AUC/time) for workload during 40-minute cycle ergometry tests at Week 24 were assessed using the generalized estimation equation (GEE) model. A cycle ergometer can measure the work performed by an individual over time during physical exercise, the work was measured every 10 minutes from 0 to 40 minutes at Baseline and Week 24. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline meas

GroupValue95% CI
UX007423.594± 295.54
Change From Baseline in Time-Adjusted-AUC for Respiratory Exchange Ratio (RER) During Cycle Ergometry at Week 24 Primary · Baseline, Week 24

Change from baseline in time-adjusted-AUC for respiratory exchange ratio (RER) during cycle ergometry at Week 24, assessed using the GEE model, which included change from baseline as dependent variable, time as categorical variable, and adjusted for baseline measurement with compound symmetry covariance structure. RER during exercise is calculated as volume of carbon dioxide/volume of oxygen. RER measures whether carbohydrates or fats are being used as fuel. RER ≥1.0 indicates carbohydrates are the predominate fuel source. RER \<1.0 and RER \>0.70 indicates both fats and carbohydrates are the

GroupValue95% CI
UX007-0.011± 0.0132
Change From Baseline in Actual Duration of Exercise During Cycle Ergometry at Week 24 Primary · Baseline, Week 24

To evaluate the impact of 24 weeks of treatment with UX007 on exercise intolerance, the change from Baseline in actual duration of exercise during 40-minute cycle ergometry tests at Week 24 was assessed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. Duration of exercise is expected to increase as exercise tolerance improves.

GroupValue95% CI
UX0074.671± 2.65
Change From Baseline in Distance Traveled During the 12-Minute Walk Test (12MWT) at Week 18 Primary · Baseline (last assessment during the 4-week run-in period), Week 18

To evaluate the impact 18 weeks of treatment with UX007 has on muscle function, the change from Baseline in distance traveled during a 12MWT at Week 18 was assessed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. Distance traveled during the 12MWT is expected to increase as muscle function increases.

GroupValue95% CI
UX007181.37± 104.63
Change From Baseline in Energy Expenditure Index (EEI) During the 12MWT at Week 18 Primary · Baseline (last assessment during the 4-week run-in period), Week 18

To evaluate the impact 18 weeks of treatment with UX007 has on muscle function, the change from Baseline of EEI during the 12MWT at Week 18 was assessed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. EEI is quantified as the post-test heart rate minus the pre-test heart rate (in beats/min) divided by overall velocity, and is valued in beats/meter. A decrease in EEI when walking a similar distance or no change when walking longer d

GroupValue95% CI
UX007-0.185± 0.09
Change From Baseline in Percentage of the Predicted 6-Minute Walk Test (6MWT) Distance Walked at Week 18 Primary · Baseline (last assessment during the 4-week run-in period), Week 18

To evaluate the impact 18 weeks of treatment with UX007 has on muscle function, the change from Baseline in the percentage of the predicted distance traveled during the first 6 minutes (6MWT) of the 12MWT at Week 18 was assessed using the GEE model. A participant's mathematical formula to calculate their percent predicted (PP) distance walked in the 6MWT was based on their demographics at baseline. For participants \< 20 years old, the formula used was referenced from (Gieger, et. al. 2007) which calculated PP distance walked based on age, gender, and height. For participants \>= 20 years old,

GroupValue95% CI
UX00712.44± 7.22
Change From Baseline in Physical Summary Score (PHS-10) of the Short Form 10 (SF-10) at Week 24 Primary · Baseline, Week 24

To evaluate the impact treatment with UX007 has on functional disability and health in participants between 5 and 17 years of age, change from Baseline in the T-scores of the PHS-10 were assessed at Week 24 and analyzed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. The SF-10 Health Survey for Children is a 10-item caregiver-completed assessment designed to measure children's health-related quality of life. The PHS-10 of the SF-1

GroupValue95% CI
UX0072.16± 2.16
Change From Baseline in Psychosocial Summary Score (PSS-10) of the SF10 at Week 24 Primary · Baseline, Week 24

To evaluate the impact treatment with UX007 has on functional disability and health in participants between 5 and 17 years of age, changes from Baseline in the T-scores of the PSS-10 were assessed at Week 24 and analyzed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. The PSS-10 of the SF-10 is scored such that higher scores indicate more favorable functioning. The T-score based scoring signifies that scale scores are centered so

GroupValue95% CI
UX0070.816± 2.63
Change From Baseline in the Physical Component Summary Scale (PCS-12) at Week 24 Primary · Baseline, Week 24

Changes from baseline in T-scores as assessed by the PCS-12 Short-Form Health Survey, version 2 (SF-12v2) at Week 24 were assessed using the GEE model, which included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. PCS-12 scores were calculated from the individual responses to those questions that contribute to physical health. Raw scores range from 0 to 100 with higher scores indicating better health. The T-score based scoring signifies that scale scores are centered so th

GroupValue95% CI
UX0078.88± 1.63
Change From Baseline in the Mental Component Summary Scale (MCS-12) at Week 24 Primary · Baseline, Week 24

Changes from baseline of T-scores as assessed by the MCS-12 of the SF-12v2 at Week 24 were assessed using the GEE model, which included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. MCS-12 scores were calculated from the individual responses to those questions that contribute to mental health. Raw scores range from 0 to 100 with higher scores indicating better health. The T-score based scoring signifies that scale scores are centered so that a score of 50 corresponds to t

GroupValue95% CI
UX0079.7± 4.0
Annualized Event Rate of All Major Clinical Events Pre- and Post-Treatment With UX007 Primary · 18 months before and after UX007 initiation

Major clinical events are defined as adverse events (AEs) resulting in hospitalizations, emergency room (ER) visits, and emergency intervention.

Pre-UX007
GroupValue95% CI
UX0071.69± 1.6081
Post-UX007
GroupValue95% CI
UX0070.877± 1.142
Annualized Duration Rate of All Major Clinical Events Pre- and Post-Treatment With UX007 Primary · 18 months before and after UX007 initiation

Major clinical events are defined as AEs resulting in hospitalizations, ER visits, and emergency intervention.

Pre-UX007
GroupValue95% CI
UX0075.961± 6.0783
Post-UX007
GroupValue95% CI
UX0072.964± 3.9733

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of UX007 through the Follow-up visit (Week 82) or 30 days following the last UX007 administration.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

UX007
Serious: 19/29 (66%)
Deaths: 0/29

Serious adverse events (26 terms)

ReactionSystemUX007
RhabdomyolysisMusculoskeletal and connective tissue disorders
GastroenteritisInfections and infestations
Gastroenteritis ViralInfections and infestations
Gastrointestinal Viral InfectionInfections and infestations
Upper Respiratory Tract InfectionInfections and infestations
Infection ProphylaxisSurgical and medical procedures
Cardiomyopathy AcuteCardiac disorders
TalipesCongenital, familial and genetic disorders
AtelectasisRespiratory, thoracic and mediastinal disorders
Gastrointestinal DisorderGastrointestinal disorders
Gastrointestinal HaemorrhageGastrointestinal disorders
VomitingGastrointestinal disorders
MenorrhagiaReproductive system and breast disorders
Metabolic DisorderMetabolism and nutrition disorders
Adenoviral Upper Respiratory InfectionInfections and infestations
Adenovirus InfectionInfections and infestations
ConjunctivitisInfections and infestations
Coxsackie Viral InfectionInfections and infestations
Croup InfectiousInfections and infestations
Otitis MediaInfections and infestations
Otitis Media AcuteInfections and infestations
Pneumonia MycoplasmalInfections and infestations
Respiratory Tract Infection ViralInfections and infestations
RoseolaInfections and infestations
Urinary Tract InfectionInfections and infestations
Other adverse events (55 terms — click to expand)

ReactionSystemUX007
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
Upper Respiratory Tract InfectionInfections and infestations
PyrexiaGeneral disorders
HeadacheNervous system disorders
Abdominal PainGastrointestinal disorders
RhabdomyolysisMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Ear InfectionInfections and infestations
NasopharyngitisInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
Abdominal Pain UpperGastrointestinal disorders
Decreased AppetiteMetabolism and nutrition disorders
BronchitisInfections and infestations
Gastroenteritis ViralInfections and infestations
Gastrointestinal Viral InfectionInfections and infestations
RhinitisInfections and infestations
Viral Upper Respiratory Tract InfectionInfections and infestations
PainGeneral disorders
Arthropod BiteInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
Blood Creatine Phosphokinase IncreasedInvestigations
Nasal CongestionRespiratory, thoracic and mediastinal disorders
Oropharyngeal PainRespiratory, thoracic and mediastinal disorders
Gastrointestinal PainGastrointestinal disorders
Gastrooesophageal Reflux DiseaseGastrointestinal disorders
AcneSkin and subcutaneous tissue disorders
ConjunctivitisInfections and infestations
GastroenteritisInfections and infestations
SinusitisInfections and infestations
Urinary Tract InfectionInfections and infestations
Melanocytic NaevusNeoplasms benign, malignant and unspecified (incl cysts and polyps)
AnxietyPsychiatric disorders
IrritabilityPsychiatric disorders
Panic AttackPsychiatric disorders
LacerationInjury, poisoning and procedural complications
Procedural PainInjury, poisoning and procedural complications
Stoma Site PainInjury, poisoning and procedural complications
Carnitine DecreasedInvestigations
TachycardiaCardiac disorders

Most-reported serious reactions: Rhabdomyolysis, Gastroenteritis, Gastroenteritis Viral, Gastrointestinal Viral Infection, Upper Respiratory Tract Infection, Infection Prophylaxis, Cardiomyopathy Acute, Talipes.

Data from ClinicalTrials.gov NCT01886378 adverse events section.

Sponsor's own description

The primary objective of the study was to evaluate the impact of UX007 on acute clinical pathophysiology associated with LC-FAOD following 24 weeks of treatment.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Results from a 78-week, single-arm, open-label phase 2 study to evaluate UX007 in pediatric and adult patients with severe long-chain fatty acid oxidation disorders (LC-FAOD).
    Vockley J, Burton B, Berry GT, Longo N, et al · · 2019 · cited 44× · PMID 30740733 · DOI 10.1002/jimd.12038
  2. Effects of triheptanoin (UX007) in patients with long-chain fatty acid oxidation disorders: Results from an open-label, long-term extension study.
    Vockley J, Burton B, Berry G, Longo N, et al · · 2021 · cited 43× · PMID 32885845 · DOI 10.1002/jimd.12313
  3. Triheptanoin: First Approval.
    Shirley M. · · 2020 · cited 26× · PMID 32897506 · DOI 10.1007/s40265-020-01399-5
  4. Patient and observer reported outcome measures to evaluate health-related quality of life in inherited metabolic diseases: a scoping review.
    Pascoal C, Brasil S, Francisco R, Marques-da-Silva D, et al · · 2018 · cited 24× · PMID 30486833 · DOI 10.1186/s13023-018-0953-9
  5. Triheptanoin for the treatment of long-chain fatty acid oxidation disorders: Final results of an open-label, long-term extension study.
    Vockley J, Burton BK, Berry G, Longo N, et al · · 2023 · cited 15× · PMID 37276053 · DOI 10.1002/jimd.12640
  6. Dietary management and major clinical events in patients with long-chain fatty acid oxidation disorders enrolled in a phase 2 triheptanoin study.
    Vockley J, Longo N, Madden M, Dwyer L, et al · · 2021 · cited 14× · PMID 33487279 · DOI 10.1016/j.clnesp.2020.11.018
  7. Strategies for correcting very long chain acyl-CoA dehydrogenase deficiency.
    Tenopoulou M, Chen J, Bastin J, Bennett MJ, et al · · 2015 · cited 6× · PMID 25737446 · DOI 10.1074/jbc.m114.635102

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