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

Primary Purpose

Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
UX007
Placebo
Sponsored by
Ultragenyx Pharmaceutical Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS) focused on measuring Glucose Transporter Type 1 Deficiency Syndrome Glut1

Eligibility Criteria

1 Year - 100 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Diagnosis of Glut1 DS confirmed by SLC2A1 mutation
  2. Males and females at least 1 of age at the time of informed consent
  3. Average of at least 2 observable seizures (generalized or partial-onset [simple partial motor, complex partial, absence, or secondarily generalized seizures) in 4 weeks over the last 24 weeks, by subject or caregiver report
  4. At least 2 observable seizures (generalized or partial-onset [simple partial motor, complex partial, or secondarily generalized seizures) in 4 weeks during the Baseline Period, with no 3-week seizure-free period during the Baseline Period OR absence seizures documented on Screening electroencephalogram (EEG)
  5. Continuing to have seizures despite a prior or current use of at least 1 antiepileptic drug (AED)
  6. Allowed to be on up to 3 concomitant AEDs that must have been stable in dose at least 2 weeks prior to the beginning of screening and anticipated to remain stable in dose through the end of the 8-week, placebo-controlled Treatment Period
  7. Not on, or not fully compliant with a prescribed diet plan (e.g. KD)
  8. Plasma level of beta-hydroxybutyrate (BHB) ≤ 1 mmol/L (non-fasting) at Screening
  9. Provide written or verbal assent (if possible) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures
  10. Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, comply with accurate completion of the seizures diary, and likely to complete the 8 week, placebo-controlled, Treatment Period
  11. Females of childbearing potential must have a negative pregnancy test at Screening, be willing to use an acceptable method of contraception, and have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have not reached menarche, had total hysterectomy, have been in menopause for at least two years, or have had tubal ligation at least one year prior to Screening.

Exclusion Criteria:

  1. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 3 times the upper limit of normal at Screening
  2. Any known hypersensitivity to triheptanoin or safflower oil that, in the judgment of the investigator, places the subject at increased risk for adverse effects
  3. Prior use of triheptanoin within 30 days prior to Screening
  4. History of, or current suicidal ideation, behavior and/or attempts
  5. Pregnant and/or breastfeeding an infant at Screening
  6. Participants unwilling or unable to discontinue use of a prohibited medication or other substance that may confound study objectives
  7. Use of any investigational product (drug or supplement, including medium chain triglyceride [MCT] oil) within 30 days prior to Screening, or at any time during the study
  8. Has a condition of such severity and acuity, in the opinion of the investigator, that it warrants immediate surgical intervention or other treatment
  9. Has a concurrent disease or condition, or laboratory abnormality that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or introduces additional safety concerns (e.g., diabetes mellitus, other concurrent neurological or psychiatric disorders)

Sites / Locations

  • Children's Hospital Colorado - University of Colorado, Denver, School of Medicine
  • Miami Children's Research Institute
  • Neurology & Epilepsy Research Center
  • Columbia University - Department of Neurology
  • Columbia University Medical Center
  • Cook Children's Hospital
  • University of Texas Neurometabolic Clinic
  • Seattle Children's Hospital
  • Melbourne Brain Centre
  • Service de Neurologie Pédiatrique et des Maladies Métaboliques - INSERM U1141 Hôpital Robert Debré - APHP
  • Sheba University Medical Center
  • Unita' Operativa Neurologia Pediatrica e Malattie Muscolari Istituto "Giannina Gaslini"
  • Hospital Sant Joan de Deu
  • Newcastle University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

UX007

Placebo

Arm Description

Participants randomized to receive UX007 enter a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continue treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).

Participants randomized to receive placebo enter a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continue treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).

Outcomes

Primary Outcome Measures

Percent Reduction From Baseline to Week 8 in Frequency of Total Seizures (Normalized to a 4-Week Rate)
Reduction from baseline to Week 8 in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary and absence seizures measured overnight by EEG. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period
An adverse event (AE) was defined as any untoward medical occurrence, whether or not considered drug related. A serious AE was defined as an AE or suspected adverse reaction that at any dose resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition. An AE was considered a TEAE if it occurred or worsened in severity on or after the date of the first dose of study drug. An AE was considered a UX007 emergent adverse event if it occurred or worsened in severity on or after the first date of first dose of UX007 during the study.
Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period
An AE was defined as any untoward medical occurrence, whether or not considered drug related. A serious AE was defined as an AE or suspected adverse reaction that at any dose resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition. An AE was considered a TEAE if it occurred or worsened in severity on or after the date of the first dose of study drug. An AE was considered a UX007 emergent adverse event if it occurred or worsened in severity on or after the first date of first dose of UX007 during the study.

Secondary Outcome Measures

Percent Reduction From Baseline to Week 8 in Frequency of Observable Seizures (Normalized to a 4-Week Rate)
Reduction from baseline to Week 8 in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. A negative value indicates an increase in frequency.
Percent Reduction From Baseline to Week 8 in Frequency of Absence Seizures (Normalized to a 4-Week Rate)
Reduction from baseline to Week 8 in frequency of absence seizures measured overnight by EEG. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
Percentage of Participants With at Least a 50% Reduction From Baseline to Week 8 in Frequency of Total Seizures
Seizure response, defined as the percentage of participants with at least 50% reduction from randomization to Week 8 in frequency of total seizures. Includes observable generalized and partial-onset seizures measured for 6 weeks by diary and absence seizures measured overnight by EEG. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec).
Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Observable Seizures
Observable seizure response, defined as the percentage of participants with at least 50% reduction from randomization to Week 8 in frequency of observable seizures. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological.
Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Absence Seizures
Absence seizure response, defined as the percentage of participants with at least 50% reduction from randomization to Week 8 in frequency of absence seizures. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec).
Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE)
CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. RTI Simple choice reaction time standard deviation (RTISRTSD) assesses the cognitive domain of attention, with scores on a continuous range from 0 to 5000; lower scores indicate better function. RTI median simple choice reaction time (RTIMDSRT) assesses the cognitive domain of reaction time, with scores on a continuous range from 100 to 5100; lower scores indicate better function. RTI median 5-choice reaction time (RTIMDFRT) assesses the cognitive domain of reaction time, with scores on a continuous range from 100 to 5100; lower scores indicate better function. GEE statistical model.
Change From Baseline to Week 8 in CANTAB, Paired Associates Learning (PAL) Scores, GEE
CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. PAL total errors adjusted (PALTEA) assesses the cognitive domain of episodic memory/new learning, with scores on a discrete, ordinal scale from 0 to 137; lower scores indicate better function. PAL first trial memory score (PALFTMS) assesses the cognitive domain of episodic memory, with scores on a discrete, ordinal scale from 0 to 27; higher scores indicate better function. GEE statistical model.
Change From Baseline to Week 8 in CANTAB, Spatial Span (SSP) Span Length Scores, GEE
CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SSP Span Length (SSPSLF) assesses the cognitive domain of sequential memory, with scores on a discrete, ordinal scale from 2 to 9; higher scores indicate better function. GEE statistical model.
Change From Baseline to Week 8 in CANTAB, Spatial Working Memory (SWM) Scores, GEE
CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SWM between errors (SWMBE48) assesses the cognitive domain of working memory, with scores on a discrete, ordinal scale from 0 to 360; lower scores indicate better function. SWM strategy (SWMS68) assesses the cognitive domain of executive function/strategy, with scores on a discrete, ordinal scale from 4 to 28; lower scores indicate better function. GEE statistical model.
Change From Baseline to Week 8 in Distance Traveled (in Meters) as Measured by 6-Minute Walk Test (6MWT)
Participants were instructed to walk the length of a pre-measured 20-30 meter course in a hallway for 6 consecutive minutes. The total distance walked (meters) in a 6 minute period was recorded.
Change From Baseline to Week 8 in Distance Traveled (in Percent Predicted) as Measured by 6MWT
Participants were instructed to walk the length of a pre-measured 20-30 meter course in a hallway for 6 consecutive minutes. The total distance walked (meters) in a 6 minute period was recorded. The percent of predicted normal distance walked was determined based on published normative data.
Time (in Minutes) to Onset of Paroxysmal Exertional Dyskinesia (PED) as Measured During 6MWT Over Time Through Week 8
For the 6MWT, subjects were instructed to walk the length of a pre-measured 20-30 meter course in a hallway for 6 consecutive minutes. The total distance walked (meters) in a 6 minute period was recorded. PED occurring during the 6MWT was assessed. (PED is characterized by transient abnormal, involuntary movements primarily affecting the legs and feet, and typically precipitated by prolonged exertion.)
Change From Baseline to Week 8 in Gross Motor Function Measure-88 (GMFM-88) Total Score
The GMFM-88 is a standardized observational measure of abilities that includes the following 5 domains: lying/rolling, sitting, crawling/kneeling, standing, and walking/running/jumping. The GMFM-88 scores include the following: Lying & Rolling Score, Range 0-100%, higher is better Sitting Score, Range 0-100%, higher is better Crawling & Kneeling Score, Range 0-100%, higher is better Standing Score, Range 0-100%, higher is better Walking, Running & Jumping Score, Range 0-100%, higher is better Total Score = (Sum of 5 Above Scores) / 5, Range 0-100%, higher is better.
Percent Reduction From Baseline Over Time in Frequency of Total Seizures (Normalized to a 4-Week Rate)
Reduction from baseline over time in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary and absence seizures measured overnight by EEG. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate)
Reduction from baseline over time in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. A negative value indicates an increase in frequency.
Percent Reduction From Baseline Over Time in Frequency of Absence Seizures (Normalized to a 4-week Rate)
Reduction from baseline to Week 8 in frequency of absence seizures measured overnight by EEG. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.

Full Information

First Posted
October 31, 2013
Last Updated
June 8, 2020
Sponsor
Ultragenyx Pharmaceutical Inc
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1. Study Identification

Unique Protocol Identification Number
NCT01993186
Brief Title
Phase 2 Study of Triheptanoin (UX007) for the Treatment of Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
February 28, 2014 (Actual)
Primary Completion Date
September 20, 2017 (Actual)
Study Completion Date
September 20, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ultragenyx Pharmaceutical Inc

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objectives of the study are to evaluate the efficacy of UX007 compared to placebo as measured by the reduction from randomization to Week 8 in frequency of seizures and to evaluate the safety of UX007 via adverse event (AE) rates, laboratory values, and electrocardiogram (ECG).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
Keywords
Glucose Transporter Type 1 Deficiency Syndrome Glut1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
UX007
Arm Type
Experimental
Arm Description
Participants randomized to receive UX007 enter a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continue treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants randomized to receive placebo enter a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continue treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).
Intervention Type
Drug
Intervention Name(s)
UX007
Other Intervention Name(s)
C7 oil, triheptanoin, glycerol triheptanoate, glycerol trienanthate, 1, 2, 3-trienanthoylglycerol, trienanthin, 2,3-di(heptanoyloxy)propyl heptanoate
Intervention Description
oral liquid
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
oral liquid
Primary Outcome Measure Information:
Title
Percent Reduction From Baseline to Week 8 in Frequency of Total Seizures (Normalized to a 4-Week Rate)
Description
Reduction from baseline to Week 8 in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary and absence seizures measured overnight by EEG. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
Time Frame
Baseline, Week 8
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period
Description
An adverse event (AE) was defined as any untoward medical occurrence, whether or not considered drug related. A serious AE was defined as an AE or suspected adverse reaction that at any dose resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition. An AE was considered a TEAE if it occurred or worsened in severity on or after the date of the first dose of study drug. An AE was considered a UX007 emergent adverse event if it occurred or worsened in severity on or after the first date of first dose of UX007 during the study.
Time Frame
Weeks 0 to 8
Title
Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period
Description
An AE was defined as any untoward medical occurrence, whether or not considered drug related. A serious AE was defined as an AE or suspected adverse reaction that at any dose resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition. An AE was considered a TEAE if it occurred or worsened in severity on or after the date of the first dose of study drug. An AE was considered a UX007 emergent adverse event if it occurred or worsened in severity on or after the first date of first dose of UX007 during the study.
Time Frame
Weeks 9 to 52 plus 30 days
Secondary Outcome Measure Information:
Title
Percent Reduction From Baseline to Week 8 in Frequency of Observable Seizures (Normalized to a 4-Week Rate)
Description
Reduction from baseline to Week 8 in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. A negative value indicates an increase in frequency.
Time Frame
Baseline, Week 8
Title
Percent Reduction From Baseline to Week 8 in Frequency of Absence Seizures (Normalized to a 4-Week Rate)
Description
Reduction from baseline to Week 8 in frequency of absence seizures measured overnight by EEG. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
Time Frame
Baseline, Week 8
Title
Percentage of Participants With at Least a 50% Reduction From Baseline to Week 8 in Frequency of Total Seizures
Description
Seizure response, defined as the percentage of participants with at least 50% reduction from randomization to Week 8 in frequency of total seizures. Includes observable generalized and partial-onset seizures measured for 6 weeks by diary and absence seizures measured overnight by EEG. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec).
Time Frame
Baseline, Week 8
Title
Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Observable Seizures
Description
Observable seizure response, defined as the percentage of participants with at least 50% reduction from randomization to Week 8 in frequency of observable seizures. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological.
Time Frame
Baseline, Week 8
Title
Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Absence Seizures
Description
Absence seizure response, defined as the percentage of participants with at least 50% reduction from randomization to Week 8 in frequency of absence seizures. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec).
Time Frame
Baseline, Week 8
Title
Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE)
Description
CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. RTI Simple choice reaction time standard deviation (RTISRTSD) assesses the cognitive domain of attention, with scores on a continuous range from 0 to 5000; lower scores indicate better function. RTI median simple choice reaction time (RTIMDSRT) assesses the cognitive domain of reaction time, with scores on a continuous range from 100 to 5100; lower scores indicate better function. RTI median 5-choice reaction time (RTIMDFRT) assesses the cognitive domain of reaction time, with scores on a continuous range from 100 to 5100; lower scores indicate better function. GEE statistical model.
Time Frame
Baseline, Week 8
Title
Change From Baseline to Week 8 in CANTAB, Paired Associates Learning (PAL) Scores, GEE
Description
CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. PAL total errors adjusted (PALTEA) assesses the cognitive domain of episodic memory/new learning, with scores on a discrete, ordinal scale from 0 to 137; lower scores indicate better function. PAL first trial memory score (PALFTMS) assesses the cognitive domain of episodic memory, with scores on a discrete, ordinal scale from 0 to 27; higher scores indicate better function. GEE statistical model.
Time Frame
Baseline, Week 8
Title
Change From Baseline to Week 8 in CANTAB, Spatial Span (SSP) Span Length Scores, GEE
Description
CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SSP Span Length (SSPSLF) assesses the cognitive domain of sequential memory, with scores on a discrete, ordinal scale from 2 to 9; higher scores indicate better function. GEE statistical model.
Time Frame
Baseline, Week 8
Title
Change From Baseline to Week 8 in CANTAB, Spatial Working Memory (SWM) Scores, GEE
Description
CANTAB measures neuropsychological function using a standardized, computerized battery of tests designed to assess visual memory, working memory, new learning and reaction time. SWM between errors (SWMBE48) assesses the cognitive domain of working memory, with scores on a discrete, ordinal scale from 0 to 360; lower scores indicate better function. SWM strategy (SWMS68) assesses the cognitive domain of executive function/strategy, with scores on a discrete, ordinal scale from 4 to 28; lower scores indicate better function. GEE statistical model.
Time Frame
Baseline, Week 8
Title
Change From Baseline to Week 8 in Distance Traveled (in Meters) as Measured by 6-Minute Walk Test (6MWT)
Description
Participants were instructed to walk the length of a pre-measured 20-30 meter course in a hallway for 6 consecutive minutes. The total distance walked (meters) in a 6 minute period was recorded.
Time Frame
Baseline, Week 8
Title
Change From Baseline to Week 8 in Distance Traveled (in Percent Predicted) as Measured by 6MWT
Description
Participants were instructed to walk the length of a pre-measured 20-30 meter course in a hallway for 6 consecutive minutes. The total distance walked (meters) in a 6 minute period was recorded. The percent of predicted normal distance walked was determined based on published normative data.
Time Frame
Baseline, Week 8
Title
Time (in Minutes) to Onset of Paroxysmal Exertional Dyskinesia (PED) as Measured During 6MWT Over Time Through Week 8
Description
For the 6MWT, subjects were instructed to walk the length of a pre-measured 20-30 meter course in a hallway for 6 consecutive minutes. The total distance walked (meters) in a 6 minute period was recorded. PED occurring during the 6MWT was assessed. (PED is characterized by transient abnormal, involuntary movements primarily affecting the legs and feet, and typically precipitated by prolonged exertion.)
Time Frame
Baseline, Week 4, Week 8
Title
Change From Baseline to Week 8 in Gross Motor Function Measure-88 (GMFM-88) Total Score
Description
The GMFM-88 is a standardized observational measure of abilities that includes the following 5 domains: lying/rolling, sitting, crawling/kneeling, standing, and walking/running/jumping. The GMFM-88 scores include the following: Lying & Rolling Score, Range 0-100%, higher is better Sitting Score, Range 0-100%, higher is better Crawling & Kneeling Score, Range 0-100%, higher is better Standing Score, Range 0-100%, higher is better Walking, Running & Jumping Score, Range 0-100%, higher is better Total Score = (Sum of 5 Above Scores) / 5, Range 0-100%, higher is better.
Time Frame
Baseline, Week 8
Title
Percent Reduction From Baseline Over Time in Frequency of Total Seizures (Normalized to a 4-Week Rate)
Description
Reduction from baseline over time in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary and absence seizures measured overnight by EEG. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
Time Frame
Baseline, Week 26, Week 31
Title
Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate)
Description
Reduction from baseline over time in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. A negative value indicates an increase in frequency.
Time Frame
Baseline, Week 26, Week 31, Week 36, Week 52
Title
Percent Reduction From Baseline Over Time in Frequency of Absence Seizures (Normalized to a 4-week Rate)
Description
Reduction from baseline to Week 8 in frequency of absence seizures measured overnight by EEG. Absence seizures from EEG include absence awake (>=10 sec), absence sleep (>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.
Time Frame
Baseline, Week 26, Week 31

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of Glut1 DS confirmed by SLC2A1 mutation Males and females at least 1 of age at the time of informed consent Average of at least 2 observable seizures (generalized or partial-onset [simple partial motor, complex partial, absence, or secondarily generalized seizures) in 4 weeks over the last 24 weeks, by subject or caregiver report At least 2 observable seizures (generalized or partial-onset [simple partial motor, complex partial, or secondarily generalized seizures) in 4 weeks during the Baseline Period, with no 3-week seizure-free period during the Baseline Period OR absence seizures documented on Screening electroencephalogram (EEG) Continuing to have seizures despite a prior or current use of at least 1 antiepileptic drug (AED) Allowed to be on up to 3 concomitant AEDs that must have been stable in dose at least 2 weeks prior to the beginning of screening and anticipated to remain stable in dose through the end of the 8-week, placebo-controlled Treatment Period Not on, or not fully compliant with a prescribed diet plan (e.g. KD) Plasma level of beta-hydroxybutyrate (BHB) ≤ 1 mmol/L (non-fasting) at Screening Provide written or verbal assent (if possible) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, comply with accurate completion of the seizures diary, and likely to complete the 8 week, placebo-controlled, Treatment Period Females of childbearing potential must have a negative pregnancy test at Screening, be willing to use an acceptable method of contraception, and have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have not reached menarche, had total hysterectomy, have been in menopause for at least two years, or have had tubal ligation at least one year prior to Screening. Exclusion Criteria: Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 3 times the upper limit of normal at Screening Any known hypersensitivity to triheptanoin or safflower oil that, in the judgment of the investigator, places the subject at increased risk for adverse effects Prior use of triheptanoin within 30 days prior to Screening History of, or current suicidal ideation, behavior and/or attempts Pregnant and/or breastfeeding an infant at Screening Participants unwilling or unable to discontinue use of a prohibited medication or other substance that may confound study objectives Use of any investigational product (drug or supplement, including medium chain triglyceride [MCT] oil) within 30 days prior to Screening, or at any time during the study Has a condition of such severity and acuity, in the opinion of the investigator, that it warrants immediate surgical intervention or other treatment Has a concurrent disease or condition, or laboratory abnormality that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or introduces additional safety concerns (e.g., diabetes mellitus, other concurrent neurological or psychiatric disorders)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Ultragenyx Pharmaceutical Inc
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital Colorado - University of Colorado, Denver, School of Medicine
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Miami Children's Research Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Neurology & Epilepsy Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32819
Country
United States
Facility Name
Columbia University - Department of Neurology
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Cook Children's Hospital
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
University of Texas Neurometabolic Clinic
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Melbourne Brain Centre
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Service de Neurologie Pédiatrique et des Maladies Métaboliques - INSERM U1141 Hôpital Robert Debré - APHP
City
Paris
State/Province
Cedex 19
ZIP/Postal Code
75935
Country
France
Facility Name
Sheba University Medical Center
City
Tel Aviv
Country
Israel
Facility Name
Unita' Operativa Neurologia Pediatrica e Malattie Muscolari Istituto "Giannina Gaslini"
City
Genova
Country
Italy
Facility Name
Hospital Sant Joan de Deu
City
Barcelona
Country
Spain
Facility Name
Newcastle University
City
Newcastle Upon Tyne
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
35441706
Citation
Striano P, Auvin S, Collins A, Horvath R, Scheffer IE, Tzadok M, Miller I, Kay Koenig M, Lacy A, Davis R, Garcia-Cazorla A, Saneto RP, Brandabur M, Blair S, Koutsoukos T, De Vivo D. A randomized, double-blind trial of triheptanoin for drug-resistant epilepsy in glucose transporter 1 deficiency syndrome. Epilepsia. 2022 Jul;63(7):1748-1760. doi: 10.1111/epi.17263. Epub 2022 May 21.
Results Reference
derived
Links:
URL
http://www.ultragenyx.com
Description
Related Info

Learn more about this trial

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

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