Phase 2 Study of Triheptanoin (UX007) for the Treatment of Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)

2014-09-29 15:57:19 | BioPortfolio


UX007 is more effective than placebo for the reduction of seizures in patients with Glut1 DS, as measured by the reduction from baseline in frequency of generalized or partial-onset seizures, including: Generalized Tonic-Clonic, Generalized Tonic, Generalized Clonic, Generalized Atonic, Partial/Focal with Secondary Generalization, Myoclonic, Myoclonic Atonic, Myoclonic Tonic, Complex Partial/Focal, and Simple Partial/Focal Motor seizures, between Weeks 2 and 8 of treatment.



UX007G-CL201 is a randomized, double-blind, placebo-controlled, parallel-group, adaptive study to assess the safety and efficacy of UX007 in Glut1 DS. The study will enroll pediatric, adolescent, and adult subjects who are currently not on, or not compliant with a ketogenic or other high fat diet. Enrolled subjects are otherwise able to maintain standard of care treatment with 1-3 AEDs throughout the duration of the study.

Beginning with the screening visit, subjects will record seizure frequency during the 6-week Baseline Period. If the subject does not meet the seizure count criteria, the subject will be considered a screen failure and will not be randomized. At the end of the Baseline Period, eligible subjects will be randomized in a 1:1 ratio to either placebo or UX007, and stratified based on baseline seizure frequency of ≤ 8 vs. > 8 observable seizures in 4 weeks. Dosing will be initiated using a 2-week titration schedule until the subject has reached 35% of total daily calories from study drug (~1-4 g/kg/day depending on age). If a subject has not reached the target of 35% of total daily calories by the end of the 2-week titration period, dose titration should continue until the maximum tolerated dose is reached.

The study will feature an adaptive component in which a single unblinded interim analysis will be conducted by an independent statistical group when approximately 16 subjects have completed the double-blind Treatment Period. If the interim analysis criteria have been met, the study will then be considered potentially pivotal, and the sample size re-estimated based on the observed treatment difference and standard deviation, for a total of 40-100 subjects. The study design will otherwise be identical before and after the interim analysis. If the interim analysis criteria are not met, the study will continue as a Phase 2 study until approximately 40 subjects have been enrolled. The pre-specified interim analysis criteria will be provided to the independent data monitoring committee (DMC). The DMC will make the decision whether to adapt the study and increase the sample size based on the pre-specified criteria.

After the initial 8-week double-blind Treatment Period, the open-label Extension Period will begin, wherein all subjects will be treated with UX007 through Week 52 of the study. A population-PK analysis at Week 26 will provide data on metabolite levels with all subjects on UX007. Following the Week 26 visit, approximately the first 40 subjects will participate in a 10-week Dose Exploration Period to assess the impact of UX007 dose level on seizure control, other clinical manifestations such as movement disorders and cognitive deficits, and tolerability. At the end of the Dose Exploration Period, the subject will continue in the open-label Extension period, maintained on the UX007 dose (as determined by the Investigator) that provided the maximum improvement in clinical status with acceptable tolerability, and continued on this dose for the duration of the study. Long term safety and maintenance of effect of UX007 will be assessed during the Extension Period.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)


UX007 (triheptanoin), Placebo Oil


Children's Hospital of Los Angeles
Los Angeles
United States




Ultragenyx Pharmaceutical Inc

Results (where available)

View Results


Published on BioPortfolio: 2014-09-29T15:57:19-0400

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A ubiquitously expressed glucose transporter that is important for constitutive, basal GLUCOSE transport. It is predominately expressed in ENDOTHELIAL CELLS and ERYTHROCYTES at the BLOOD-BRAIN BARRIER and is responsible for GLUCOSE entry into the BRAIN.

A major glucose transporter found in NEURONS.

A glucose transport facilitator that is expressed primarily in PANCREATIC BETA CELLS; LIVER; and KIDNEYS. It may function as a GLUCOSE sensor to regulate INSULIN release and glucose HOMEOSTASIS.

A glucoside-derived SODIUM-GLUCOSE TRANSPORTER 2 inhibitor that stimulates urinary excretion of glucose by suppressing renal glucose reabsorption. It is used to manage BLOOD GLUCOSE levels in patients with TYPE 2 DIABETES.

A glucose transport protein found in mature MUSCLE CELLS and ADIPOCYTES. It promotes transport of glucose from the BLOOD into target TISSUES. The inactive form of the protein is localized in CYTOPLASMIC VESICLES. In response to INSULIN, it is translocated to the PLASMA MEMBRANE where it facilitates glucose uptake.

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