Clinical trial NCT01993186: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
Keywords: Glucose Transporter Type 1 Deficiency Syndrome Glut1
Lead sponsor: Ultragenyx Pharmaceutical Inc
Sponsor class: INDUSTRY
First posted: 2013-11-25
Enrollment: 36
Sex: ALL
Minimum age (years): 1
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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)

Primary outcomes:
measure: Percent Reduction From Baseline to Week 8 in Frequency of Total Seizures (Normalized to a 4-Week Rate)
timeFrame: Baseline, Week 8
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period
timeFrame: Weeks 0 to 8
measure: Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period
timeFrame: Weeks 9 to 52 plus 30 days
Secondary outcomes:
measure: Percent Reduction From Baseline to Week 8 in Frequency of Observable Seizures (Normalized to a 4-Week Rate)
timeFrame: Baseline, Week 8
measure: Percent Reduction From Baseline to Week 8 in Frequency of Absence Seizures (Normalized to a 4-Week Rate)
timeFrame: Baseline, Week 8
measure: Percentage of Participants With at Least a 50% Reduction From Baseline to Week 8 in Frequency of Total Seizures
timeFrame: Baseline, Week 8
measure: Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Observable Seizures
timeFrame: Baseline, Week 8
measure: Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Absence Seizures
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 8 in Cambridge Neuropsychological Test Automated Battery (CANTAB), Reaction Time (RTI) Scores, Generalized Estimating Equation (GEE)
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 8 in CANTAB, Paired Associates Learning (PAL) Scores, GEE
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 8 in CANTAB, Spatial Span (SSP) Span Length Scores, GEE
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 8 in CANTAB, Spatial Working Memory (SWM) Scores, GEE
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 8 in Distance Traveled (in Meters) as Measured by 6-Minute Walk Test (6MWT)
timeFrame: Baseline, Week 8
measure: Change From Baseline to Week 8 in Distance Traveled (in Percent Predicted) as Measured by 6MWT
timeFrame: Baseline, Week 8
measure: Time (in Minutes) to Onset of Paroxysmal Exertional Dyskinesia (PED) as Measured During 6MWT Over Time Through Week 8
timeFrame: Baseline, Week 4, Week 8
measure: Change From Baseline to Week 8 in Gross Motor Function Measure-88 (GMFM-88) Total Score
timeFrame: Baseline, Week 8
measure: Percent Reduction From Baseline Over Time in Frequency of Total Seizures (Normalized to a 4-Week Rate)
timeFrame: Baseline, Week 26, Week 31
measure: Percent Reduction From Baseline Over Time in Frequency of Observable Seizures (Normalized to a 4-Week Rate)
timeFrame: Baseline, Week 26, Week 31, Week 36, Week 52
measure: Percent Reduction From Baseline Over Time in Frequency of Absence Seizures (Normalized to a 4-week Rate)
timeFrame: Baseline, Week 26, Week 31
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado - University of Colorado, Denver, School of Medicine
state: Colorado
city: Miami
country: United States
facility: Miami Children's Research Institute
state: Florida
city: Orlando
country: United States
facility: Neurology & Epilepsy Research Center
state: Florida
city: New York
country: United States
facility: Columbia University - Department of Neurology
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Fort Worth
country: United States
facility: Cook Children's Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas Neurometabolic Clinic
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Heidelberg
country: Australia
facility: Melbourne Brain Centre
state: Victoria
city: Paris
country: France
facility: Service de Neurologie Pédiatrique et des Maladies Métaboliques - INSERM U1141 Hôpital Robert Debré - APHP
state: Cedex 19
city: Tel Aviv
country: Israel
facility: Sheba University Medical Center
city: Genova
country: Italy
facility: Unita' Operativa Neurologia Pediatrica e Malattie Muscolari Istituto "Giannina Gaslini"
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle University
Study officials:
affiliation: Ultragenyx Pharmaceutical Inc
name: Medical Director
role: STUDY_DIRECTOR
References:
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.