Study to Assess the Long Term Safety and Efficacy of UX007 in Participants With Glucose Type 1 Deficiency Syndrome (Glut1 DS)

An Open-label Extension Study to Assess the Long-term Safety and Efficacy of UX007 in Subjects With Glucose Transporter Type 1 Deficiency Syndrome

The primary objective of the study is to evaluate the long-term safety of UX007 in Glut1 DS participants.

Study Overview

• Status: Terminated
• Conditions: Glucose Transporter Type 1 Deficiency Syndrome
• Intervention / Treatment: Drug: UX007

Detailed Description

The study will enroll up to 40 pediatric, adolescent and adult Glut 1 DS participants who have completed the UX007G-CL201 (NCT019933186) study and, at the discretion of the Sponsor, additional participants from other clinical studies, investigator sponsored trials (ISTs), or expanded access/compassionate use treatment.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Melbourne Brain Centre
• Denmark
  • Copenhagen, Denmark, 2100
    • Copenhagen University Hospital
• Spain
  • Barcelona, Spain, 08950
    • Hospital Sant Joan de Deu
• United Kingdom
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • The Newcastle Upon Tyne Hospitals NHS Foundation Trust
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado - University of Colorado, Denver, School of Medicine
  • Florida
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Glut 1 DS confirmed by cerebrospinal fluid glucose concentration. erythrocyte 3-O-methyl-D-glucose uptake assay, or solute carrier family 2 member 1 (SLC2A1) molecular genetic testing (Information obtained from Medical Records)
• Males and females aged at least 1 year old at the time of informed consent
• Completion of UX007G-CL201 study (NCT01993186). Glut1 DS patients who received UX007/triheptanoin treatment as apart of clinical studies, ISTs or expanded access/compassionate use treatment programs may be eligible at the discretion of the Sponsor
• Provide written informed consent or verbal assent (if possible) with 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, and comply with accurate completion of the seizure diary
• Females of childbearing potential must have a negative urine pregnancy test at Baseline and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have not experienced menarche, are post-menopausal (defined as having no menses for at least 12 months without an alternative medical cause), or are permanently sterile due to total hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.
• Participants of child-bearing potential or fertile males with partners of child-bearing potential who are sexually active must consent to use a highly-effective method of contraception as determined by the investigator from the period following the signing of the informed consent through 30 days after last dose of study drug.

Exclusion Criteria:

• Any known hypersensitivity to triheptanoin, that in the judgement of the investigator, places the subject at an increased risk for adverse effects
• History of, or current suicidal ideation, behavior and/or attempts
• Pregnant and/or breast feeding an infant
• Unwilling or unable to discontinue use of prohibited medication (barbiturates, pancreatic lipase inhibitors) or other substance that may confound study objectives. Use of up to 3 concomitant antiepileptic drugs is allowed, provided dose has been stable at least 14 days prior to Baseline
• Use of any Investigational Product, drug or supplement (other than UX007) within 30 days prior to Baseline, 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 introduce additional safety concerns

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UX007; UX007 dosing targeted and/or maintained at 35% of total daily caloric intake.	Drug: UX007; UX007 is a liquid intended for oral (PO) administration.; Other Names: Triheptanoin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Deaths	An adverse event (AE) was defined as any untoward medical occurrence, whether or not considered drug related. Serious adverse events (SAEs) are AEs that at any dose, in the view of either the investigator or sponsor, results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or disability; a congenital anomaly/birth defect; other important medical event. An AE was considered a TEAE if it occurred on or after the first dose in this study, and was not present prior to the first dose in this study, or it was present at the first dose in this study but increased in severity during the study. Severity was based on Common Terminology Criteria for Adverse Events (CTCAE): 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, and 5 = death related to AE.	From first dose of study drug up to 36 months. The mean (SD) treatment duration was 667.9 (357) days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline Over Time in Overall Seizure Frequency Per 4 Weeks	The number of observable seizures were recorded by the subject or caregiver via diary throughout the study. Observable seizures were defined as: 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; absence.	Baseline (from NCT01993186), Month 0-3, Month 4-6, Month 7-9, Month 10-12, Month 13-18, Month 19-24, Month 25-30, Month 31-36
Change From Baseline Over Time in CNS Total Score	The CNS evaluates measures of neurological function and development delay, and is the sum of scores for the following domains: Weight, Height, Head Circumference, General Medical Exam, Funduscopic Exam, Cranial Nerves, Stance & Gait, Involuntary Movements, Sensation, Cerebellar Function, Muscle Bulk, Tone & Strength, Myotatic Reflexes, Toe Sign, Other Findings. The CNS is only scored when all domains are measured and ranges from 0 (abnormal exam) to 76 (normal exam). Higher scores are associated with higher neurological function.	Baseline (from NCT01993186), Month 0, Month 6, Month 12, Month 24, Month 36
Change From Baseline Over Time in SF-10 Health Survey for Children Physical Summary Score	The SF-10 Health Survey for Children was administered to caregivers of participants aged 5-17 years. Responses are used to generate 2 component summary scores: Physical Summary Score and the Psychosocial Summary Score. The T-score based scale scores were centered so that a score of 50 corresponds to the average score in a comprehensive 2006 sample (a combination of general population and supplemental disability and chronic condition samples). Higher scores are associated with better quality of life.	Baseline (from NCT01993186), Month 0, Month 6, Month 12, Month 18, Month 24, Month 30
Change From Baseline Over Time in SF-10 Health Survey for Children Psychosocial Summary Score	The SF-10 Health Survey for Children was administered to caregivers of participants aged 5-17 years. Responses are used to generate 2 component summary scores: Physical Summary Score and the Psychosocial Summary Score. The T-score based scale scores were centered so that a score of 50 corresponds to the average score in a comprehensive 2006 sample (a combination of general population and supplemental disability and chronic condition samples). Higher scores are associated with better quality of life.	Baseline (from NCT01993186), Month 0, Month 6, Month 12, Month 18, Month 24, Month 30
Change From Baseline Over Time in SF-12v2 Health Survey PCS Score	SF-12v2 was assessed for adults 18 years of age and older. Eight domain scores were used to generate 2 component summary scores: physical health (PCS) and mental health (MCS). The PCS and MCS scores have mean of 50 and SD of 10. The T-score based scoring method scores the data in relation to U.S. general population T-scores. Therefore, all scores obtained that are below 50 can be interpreted as below the U.S. general population T-score and scores above 50 can be interpreted as above the U.S. general population T-score. Higher global scores are associated with better quality of life.	Baseline (from NCT01993186), Month 0, Month 6, Month 12, Month 18
Change From Baseline Over Time in SF-12v2 Health Survey MCS Score	SF-12v2 was assessed for adults 18 years of age and older. Eight domain scores were used to generate 2 component summary scores: physical health (PCS) and mental health (MCS). The PCS and MCS scores have mean of 50 and SD of 10. The T-score based scoring method scores the data in relation to U.S. general population T-scores. Therefore, all scores obtained that are below 50 can be interpreted as below the U.S. general population T-score and scores above 50 can be interpreted as above the U.S. general population T-score. Higher global scores are associated with better quality of life.	Baseline (from NCT01993186), Month 0, Month 6, Month 12, Month 18

Collaborators and Investigators

• Sponsor: Ultragenyx Pharmaceutical Inc

Publications and helpful links

Helpful Links

• Company Website

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2015
• Primary Completion (Actual): October 22, 2019
• Study Completion (Actual): October 22, 2019

Study Registration Dates

• First Submitted: November 3, 2015
• First Submitted That Met QC Criteria: November 5, 2015
• First Posted (Estimate): November 9, 2015

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 3, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Glut 1 DS
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Syndrome; Carbohydrate Metabolism, Inborn Errors
• Other Study ID Numbers: UX007G-CL202; 2015-000389-69 (EudraCT Number)