Crossover Study to Assess the Efficacy and Safety of UX007 in the Treatment of Movement Disorders Associated With Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02960217
• Date of registration: 07/11/2016
• Prospective Registration: Yes
• Primary sponsor: Ultragenyx Pharmaceutical Inc
• Public title: Crossover Study to Assess the Efficacy and Safety of UX007 in the Treatment of Movement Disorders Associated With Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
• Scientific title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Crossover Study to Assess the Efficacy and Safety of UX007 in the Treatment of Movement Disorders Associated With Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
• Date of first enrolment: April 19, 2017
• Target sample size: 44
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02960217
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

France, Germany, Israel, Italy, Spain, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Ultragenyx Pharmaceutical Inc

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Diagnosis of Glut1 DS confirmed by SLC2A1 mutation

2. Males and females, aged =6 years old at the time of informed consent

3. At least 8 disabling paroxysmal movement disorder events in the 12 weeks prior to the
Screening, by subject or caregiver report or At least 6 disabling paroxysmal movement
disorder events in any 6 consecutive week period, over the last 12 week period prior
to the Screening, by subject or caregiver report

4. At least 4 disabling paroxysmal movement disorder events in 6 week Run-in Period,
reported in the daily electronic Glut1 DS symptom diary

5. =80% compliance with daily electronic Glut1 DS symptom diary completion during the Run
in Period

6. Not on ketogenic diet (KD), modified KD, or ketosis-inducing modified-fat diet for at
least 3 months prior to Screening

7. Plasma level of beta-hydroxybutyrate (BHB) = 1 mmol/L (non-fasting) at Screening

8. Provide written or verbal assent (if possible) and written informed consent by the
patient(if an adult), or by a legally authorized representative after the nature of
the study has been explained, and prior to any research-related procedures

9. Must, in the opinion of the Investigator, be willing and able to complete key aspects
of the study and be likely to complete the 22-week, placebo-controlled, treatment
period

10. Patient (or caregiver) must, in the opinion of the Investigator, be able to comply
with accurate completion of the study daily electronic Glut1 DS symptom diary

11. Females of child-bearing potential must have a negative urine pregnancy test at
Screening and Baseline and be willing to have additional pregnancy tests during the
study. Females considered not to be of child-bearing 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.

12. 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 site Investigator from the period
following the signing of the informed consent through 30 days after last dose of study
drug

Exclusion Criteria:

1. Any known hypersensitivity to triheptanoin or safflower oil that, in the judgment of
the Investigator, places the subject at increased risk for adverse effects

2. Prior use of triheptanoin within 30 days prior to Screening

3. History of, or current suicidal ideation, behavior and/or attempts per Columbia
Suicide Severity Rating Scale (C-SSRS) at Screening or Baseline

4. Pregnant and/or breastfeeding an infant at Screening or Baseline

5. Participants unwilling or unable to discontinue use of a prohibited medication or
other substance that may confound study objectives (medium chain triglyceride [MCT]
oil, barbiturates, pancreatic lipase inhibitors, KetoCal or other KD supplements,
and/or KD])

6. Glut1 DS treatment regimen, including antiepileptic drugs (AEDs), should be stable for
at least 30 days prior to Screening

7. Use of any investigational product (drug, medical food, or supplement, including MCT
oil, including coconut oil) within 30 days prior to Screening

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

9. Feeding or nutrition that, in the opinion of the dietitian, potentially affects
consistent administration of study drug



Age minimum: 6 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)

Intervention(s)

Drug: Placebo

Drug: UX007

Primary Outcome(s)

Baseline and Post-Baseline Columbia Suicide Severity Rating Scale (C-SSRS) Responses During Double-Blind Treatment Period [Time Frame: Baseline, up to Week 22]

Maintenance Phase Movement Disorder Frequency [Time Frame: Maintenance Phase (up to Week 22)]

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs [Time Frame: From first dose of study drug through 30-35 days after final dose. Mean (SD) treatment duration was 65.7 (12.06) and 68.3 (7.04) days for double-blind UX007 and placebo, and 305.0 (122.71) days for open-label UX007.]

Secondary Outcome(s)

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Anxiety Score at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Sleep Disturbance Score at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Baseline in CANTAB, Paired Associates Learning First Trial Memory Score (PALFTMS) at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Fatigue Score at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Period Baseline in CANTAB, Spatial Working Memory Strategy (SWMS) Scores at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Pain Interference Score at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Social Roles and Activities Score at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Mobility Score at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Clinical Global Impression - Improvement (CGI-I) at Treatment Week 10 [Time Frame: Week 10]

Duration of Movement Disorder Events During Maintenance Phase [Time Frame: Maintenance Phase (up to 22 weeks)]

Change From Period Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Health Assessment Questionnaire (Adult Form) Physical Function Score at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Baseline in CANTAB, Paired Associates Learning Total Errors (PALTEA) at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Adult Form) Cognitive Function Score at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Pain Interference Score at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Period Baseline in 12 Minute Walk Test (12MWT) Distance at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Peer Relationships Score at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Period Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB), Spatial Span (SSP) Span Length Scores at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Fatigue Score at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Period Baseline in PROMIS Health Assessment Questionnaire (Pediatric/Parent-Proxy Form) Upper Extremity Score at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Change From Period Baseline in CANTAB, Spatial Working Memory Between Errors (SWMBE) Scores at Treatment Week 10 [Time Frame: Period Baseline (defined as the last non-missing assessment prior to or on the date of the first dose of study drug for each double-blind Treatment Period), Week 10]

Secondary ID(s)

UX007G-CL301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 24/04/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02960217