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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc Identifier:
First received: October 31, 2013
Last updated: September 24, 2014
Last verified: September 2014

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.

Condition Intervention Phase
Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
Drug: UX007 (triheptanoin)
Drug: Placebo Oil
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Adaptive Study to Assess the Safety and Efficacy of UX007 in Subjects With Glucose Transporter Type 1 Deficiency Syndrome

Resource links provided by NLM:

Further study details as provided by Ultragenyx Pharmaceutical Inc:

Primary Outcome Measures:
  • 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: 6 weeks ] [ Designated as safety issue: Yes ]
  • Evaluate the safety of UX007 via adverse event (AE) rates, laboratory values, and electrocardiogram (ECG) [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Seizure Response Rate, defined as the percentage of subjects with at least a 50% reduction in seizures relative to baseline. [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  • Electroencephalography: Abnormalities on EEG (including absence seizures) recorded with an overnight EEG. Key measures include: (1) frequency of EEG seizures (including absence), and (2) frequency of interictal epileptiform discharges [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  • Change from baseline in cognitive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in distance walked as measured by 6 Minute Walk Test (6MWT) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Time to onset of paroxysmal exertional dyskinesia (PED) as measured during 6 minute walk test (6MWT) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in gross motor function using the Gross Motor Function Measure-88 (GMFM-88) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Change from baseline in neurological function using the Columbia Neurological Score (CNS) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in physician global impression of change in clinical status using the Clinical Global Impression - Severity scale (CGI-S) and Clinical Global Impression - Improvement scale (CGI-I) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in receptive vocabulary using the Peabody Picture Vocabulary Test (PPVT) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in patient or caregiver-reported quality of life using Short Form-10™ (SF-10) Health Survey for Children or Short Form-12™ (SF-12) for adults [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in functional disability by caregiver report using the Pediatric Evaluation of Disability Inventory - Computer Adaptive Test (PEDI-CAT) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in gait, using gait analysis by computerized mat (at select sites). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK) properties of UX007 Plasma Peak [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics (PK) properties of UX007 Metabolites [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  • The number of observable absence and other seizures types not analysed in the primary analysis recorded via diary. [ Time Frame: 52 eeks ] [ Designated as safety issue: Yes ]
  • Beery-Buktenica Developmental Test of Visual Motor Integration: Visual-motor integration measured using a design copy test administered by a clinician (at select sites) [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
  • Raven's Coloured Progressive Matrices: Spatial understanding and abstract reasoning using picture tests administered by a clinician (at select sites) [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: January 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: UX007 (triheptanoin)
Oral liquid administered with food 4 times a day to make up to 35% of total caloric intake. 52 weeks.
Drug: UX007 (triheptanoin)
Triheptanoin is a triglyceride composed of three heptanoate (C7 fatty acid) esters. UX007 is manufactured by chemical synthesis from glycerol and heptanoic acid. UX007 (triheptanoin) is a liquid, intended for oral (PO) administration.
Other Names:
  • C7 oil
  • Triheptanoin
  • glycerol triheptanoate
  • glycerol trienanthate
  • 1, 2, 3-trienanthoylglycerol
  • trienanthin
  • 2,3-di(heptanoyloxy)propyl heptanoate
Placebo Comparator: Placebo Oil
Placebo oil matching color and appearance of UX007.
Drug: Placebo Oil

Detailed Description:


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.


Ages Eligible for Study:   1 Year to 35 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Diagnosis of Glut1 DS confirmed by SLC2A1 mutation
  2. Males and females, aged 1 - 35 years (inclusive) at the time of informed consent
  3. Average of at least 4 observable seizures (generalized [except absence] or partial-onset [simple partial motor, complex partial, or secondarily generalized] seizures) in 4 weeks over the last 24 weeks, by subject or caregiver report
  4. At least 4 observable seizures (generalized [except absence] 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
  5. Continuing to have seizures despite a prior or current use of at least 1 AED
  6. Allowed to be on 1 - 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. ketogenic diet) comprised of at least 60% total daily caloric intake from fat during previous 14 days (confirmed by 3-day diet diary at Screening), or at any time during the course of the trial
  8. Plasma level of beta-hydroxybutyrate (BHB) ≤ 1 mmol/L (non-fasting) at Screening
  9. Naïve to triheptanoin
  10. 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
  11. 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
  12. 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 ALT or AST levels exceeding 2X 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. History of, or current suicidal ideation, behavior and/or attempts
  4. Breastfeeding an infant at Screening
  5. Participants unwilling or unable to discontinue use of a prohibited medication or other substance that may confound study objectives
  6. Use of any investigational product (drug or supplement, including MCT oil) within 30 days prior to Screening, or at any time during the study
  7. Has a condition of such severity and acuity, in the opinion of the investigator, that it warrants immediate surgical intervention or other treatment
  8. 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01993186

Contact: Julia Martinisi 415.483.8815
Contact: Leigh Stott 415-483-8857

United States, California
Children's Hospital of Los Angeles Recruiting
Los Angeles, California, United States, 20027
Contact: Vanessa Guzman    323-361-4910   
Principal Investigator: Divya Vats, MD         
United States, Colorado
Children's Hospital Colorado - University of Colorado, Denver, School of Medicine Recruiting
Aurora, Colorado, United States, 80045
Contact: Nanastasia Welnick    720-777-8608   
Principal Investigator: Abigail Collins, MD         
United States, Florida
Neurology & Epilepsy Research Center Recruiting
Orlando, Florida, United States, 32819
Contact: Barbara Peters    407-293-1122 ext 222   
Principal Investigator: Ronald Davis, MD         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago - Epilepsy Center Recruiting
Chicago, Illinois, United States, 60611
Contact: Diana Umanzor    312-227-4517   
Principal Investigator: Srishti Nangia, MD         
United States, New York
Columbia University - Department of Neurology Recruiting
New York, New York, United States, 10032
Contact: Kristen Engelstad    212-305-6834   
Contact: Jonathan Marra    212-305-2461   
Principal Investigator: Darryl De Vivo, MD         
United States, Texas
Cook Children's Hospital Recruiting
Fort Worth, Texas, United States, 76104
Contact: Juli A Ramirez    682-885-7860   
Principal Investigator: Adrian R Lacy, MD         
University of Texas Neurometabolic Clinic Recruiting
Houston, Texas, United States, 77030
Contact: Mary Kay Koenig, MD    713-500-7147      
Principal Investigator: Mary Kay Koenig, MD         
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: Laurie Guidry    206-987-0058   
Principal Investigator: Russell Saneto, DO, PhD         
Service de Neurologie Pédiatrique et des Maladies Métaboliques - INSERM U1141 Hôpital Robert Debré - APHP Not yet recruiting
Paris, Cedex 19, France, 75935
Contact: Stéphane Auvin, MD, PhD    +33 140 035 724   
Principal Investigator: Stéphane Auvin, MD, PhD         
Unita' Operativa Neurologia Pediatrica e Malattie Muscolari Istituto "Giannina Gaslini" Recruiting
Genova, Italy
Contact: Pasquale Striano, MD    +39 (0)10 56362758   
Principal Investigator: Pasquale Striano, MD         
United Kingdom
Newcastle University Not yet recruiting
Newcastle Upon Tyne, United Kingdom
Contact: Rita Horvath    +44 191 2418855   
Principal Investigator: Rita Horvath, MD         
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
  More Information

Additional Information:
No publications provided

Responsible Party: Ultragenyx Pharmaceutical Inc Identifier: NCT01993186     History of Changes
Other Study ID Numbers: UX007G-CL201
Study First Received: October 31, 2013
Last Updated: September 24, 2014
Health Authority: United States: Food and Drug Administration
Italy: The Italian Medicines Agency (AIFA)

Keywords provided by Ultragenyx Pharmaceutical Inc:
Glucose Transporter Type 1 Deficiency Syndrome Glut1

Additional relevant MeSH terms:
Carbohydrate Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Metabolism, Inborn Errors
Pathologic Processes
Cryoprotective Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents processed this record on November 24, 2014