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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Study to Assess the Safety and Efficacy of UX007 in Subjects With Glucose Transporter Type 1 Deficiency Syndrome

Brief Summary: 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, Absence and Simple Partial/Focal Motor seizures

Detailed Summary:

STUDY DESIGN AND METHODOLOGY:

UX007G-CL201 is a randomized, double-blind, placebo-controlled, parallel-group, 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 3:1 ratio to either UX007 or placebo. 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.

Phase 2 study will enroll approximately 40 subjects. 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 Explo
Sponsor: Ultragenyx Pharmaceutical Inc

Current Primary Outcome:

  • Efficacy of UX007 compared to placebo as measured by reduction from randomization to week 8 in frequency of seizures. Observable generalized and partial-onset seizures measured by diary [ Time Frame: 6 weeks ]
  • Evaluate the safety of UX007 via adverse event (AE) rates, laboratory values, and electrocardiogram (ECG) [ Time Frame: 52 weeks ]
  • Efficacy of UX007 compared to placebo as measured by reduction from randomization to week 8 in frequency of absence seizures measured overnight by EEG [ Time Frame: 6 weeks ]


Original Primary Outcome:

  • Evaluate the efficacy of UX007 compared to placebo, between Weeks 2 and 8 of treatment, as measured by the reduction from baseline in frequency of generalized or partial-onset seizures [ Time Frame: 52 weeks ]
  • Evaluate the safety of UX007 via adverse event (AE) rates, laboratory values, and electrocardiogram (ECG) [ Time Frame: 52 weeks ]


Current Secondary Outcome:

  • Efficacy of UX007 compared to placebo as measured by Seizure Response Rate, defined as the percentage of subjects with at least a 50% reduction from randomization to week 8 in frequency of seizures. [ Time Frame: 6 weeks ]
  • Efficacy of UX007 compared to placebo as measured by Change from randomization to week 8 in cognitive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB) [ Time Frame: 6 weeks ]
  • Efficacy of UX007 compared to placebo as measured by Change from randomization to Week 8 in distance walked as measured by 6 Minute Walk Test (6MWT) [ Time Frame: 6 weeks ]
  • Efficacy of UX007 compared to placebo as measured by Time to onset of paroxysmal exertional dyskinesia (PED) as measured during 6 minute walk test (6MWT) from randomization to week 8 [ Time Frame: 6 weeks ]
  • Efficacy of UX007 compared to placebo as measured by Change from baseline in gross motor function using the Gross Motor Function Measure-88 (GMFM-88) [ Time Frame: 6 weeks ]
  • Evaluate long term efficacy as measured by changes from randomization in frequency of seizures over time through week 52 [ Time Frame: 52 weeks ]
  • Evaluate the optimal dose to control seizures and impact on other clinical manifestations during the dose exploration period as measured by reduction in seizures [ Time Frame: 52 weeks ]


Original Secondary Outcome:

  • Seizure response rate, defined as the percentage of subjects with at least 50% reduction from baseline in generalized or partial-onset seizures [ Time Frame: 52 weeks ]
  • Change from baseline in frequency of seizure activity as measured by electroencephalography (EEG) abnormalities [ Time Frame: 52 weeks ]
  • Change from baseline in cognitive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB) [ Time Frame: 52 weeks ]
  • Change from baseline in distance walked as measured by 6 Minute Walk Test (6MWT) [ Time Frame: 52 weeks ]
  • Time to onset of paroxysmal exertional dyskinesia (PED) as measured during 6 minute walk test (6MWT) [ Time Frame: 52 weeks ]
  • Change from baseline in gross motor function using the Gross Motor Function Measure-88 (GMFM-88) [ Time Frame: 52 weeks ]


Information By: Ultragenyx Pharmaceutical Inc

Dates:
Date Received: October 31, 2013
Date Started: April 2014
Date Completion: October 2017
Last Updated: February 6, 2017
Last Verified: February 2017