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

• ClinicalTrials.gov Identifier: NCT02599961
• Recruitment Status: Terminated
• First Posted: November 9, 2015
• Results First Posted: April 30, 2020
• Last Update Posted: June 11, 2020
• Sponsor: Ultragenyx Pharmaceutical Inc
• Information provided by (Responsible Party): Ultragenyx Pharmaceutical Inc

Tracking Information

• First Submitted Date: November 3, 2015
• First Posted Date: November 9, 2015
• Results First Submitted Date: April 17, 2020
• Results First Posted Date: April 30, 2020
• Last Update Posted Date: June 11, 2020
• Actual Study Start Date: September 10, 2015
• Actual Primary Completion Date: October 22, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 17, 2020)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Discontinuations Due to TEAEs, and Deaths [ Time Frame: From first dose of study drug up to 36 months. The mean (SD) treatment duration was 667.9 (357) days. ]

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.

Original Primary Outcome Measures (submitted: November 5, 2015)

Frequency of AEs and SAEs [ Time Frame: 3 years ]

Frequency of Adverse Events and Serious Adverse Events assessed as related to study drug

Current Secondary Outcome Measures (submitted: April 17, 2020)

• Change From Baseline Over Time in Overall Seizure Frequency Per 4 Weeks [ Time Frame: 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 ]
  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.
• Change From Baseline Over Time in CNS Total Score [ Time Frame: Baseline (from NCT01993186), Month 0, Month 6, Month 12, Month 24, Month 36 ]
  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.
• Change From Baseline Over Time in SF-10 Health Survey for Children Physical Summary Score [ Time Frame: Baseline (from NCT01993186), Month 0, Month 6, Month 12, Month 18, Month 24, Month 30 ]
  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.
• Change From Baseline Over Time in SF-10 Health Survey for Children Psychosocial Summary Score [ Time Frame: Baseline (from NCT01993186), Month 0, Month 6, Month 12, Month 18, Month 24, Month 30 ]
  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.
• Change From Baseline Over Time in SF-12v2 Health Survey PCS Score [ Time Frame: Baseline (from NCT01993186), Month 0, Month 6, Month 12, Month 18 ]
  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.
• Change From Baseline Over Time in SF-12v2 Health Survey MCS Score [ Time Frame: Baseline (from NCT01993186), Month 0, Month 6, Month 12, Month 18 ]
  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.

Original Secondary Outcome Measures (submitted: November 5, 2015)

• Maintenance of reduction in seizure frequency [ Time Frame: 3 years ]
• Long term Efficacy of UX007 [ Time Frame: 3 years ]
  Long term efficacy in measures of neurological function and development delay using the Cambridge Neuropsychological Test Automated Battery (CANTAB)
• Long term Efficacy of UX007 [ Time Frame: 3 years ]
  Long term efficacy in measures of neurological function and development delay using the Columbia Neurological Score
• Maintenance of UX007 treatment effect on gross motor function and movement disorders using the 6 Minute Walk Test [ Time Frame: 3 years ]
• Maintenance of UX007 treatment effect on gross motor function and movement disorders using Paroxymal Exertional Dyskinesia (PED) [ Time Frame: 3 years ]
• Continued impact of UX007 treatment on clinical status and health related quality of life using the Clinical Global Impression Scales [ Time Frame: 3 years ]
• Continued impact of UX007 treatment on clinical status and health related quality of life using the Short Form Health Surveys [ Time Frame: 3 years ]
• Continued impact of UX007 treatment on clinical status and health related quality of life using thePediatric Evaluations of Disability Inventory Computer Adaptive Test (PEDI-CAT) [ Time Frame: 3 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Assess the Long Term Safety and Efficacy of UX007 in Participants With Glucose Type 1 Deficiency Syndrome (Glut1 DS)
• Official Title: An Open-label Extension Study to Assess the Long-term Safety and Efficacy of UX007 in Subjects With Glucose Transporter Type 1 Deficiency Syndrome
• Brief Summary: The primary objective of the study is to evaluate the long-term safety of UX007 in Glut1 DS participants.
• 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
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Glucose Transporter Type 1 Deficiency Syndrome

Intervention

Drug: UX007

UX007 is a liquid intended for oral (PO) administration.

Other Name: Triheptanoin

Study Arms

Experimental: UX007

UX007 dosing targeted and/or maintained at 35% of total daily caloric intake.

Intervention: Drug: UX007

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 19, 2018): 15
• Original Estimated Enrollment (submitted: November 5, 2015): 40
• Actual Study Completion Date: October 22, 2019
• Actual Primary Completion Date: October 22, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Denmark, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT02599961
• Other Study ID Numbers: UX007G-CL202; 2015-000389-69 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ultragenyx Pharmaceutical Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Ultragenyx Pharmaceutical Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Ultragenyx Pharmaceutical Inc

• PRS Account: Ultragenyx Pharmaceutical Inc
• Verification Date: June 2020