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)

NCT02960217 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: UX007G-CL301
• Study Type: interventional
• Target: 44
• Locations: 6 countries
• Sites: 12

Brief Summary

The primary objective of the study was to evaluate the efficacy and safety of UX007 in the treatment of disabling paroxysmal movement disorders associated with Glut1 DS.

Conditions

Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)

Outcome Measures

Primary Outcomes (3)

• Maintenance Phase Movement Disorder Frequency

  The frequency of paroxysmal movement disorders captured as disabling movement disorder events (normalized to a 4-week rate) observed during the Maintenance Phase in participants treated with UX007 versus placebo, as recorded by the subject/caregiver in an event-based daily Glut1 DS symptom diary.

  Maintenance Phase (up to Week 22)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and Discontinuations Due to TEAEs

  An Adverse Event (AE) was defined as any untoward medical occurrence, whether or not considered drug related. Serious adverse events (SAE) was defined as an AE that at any dose, in the view of either the Investigator or Ultragenyx, 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 (substantial disruption of the ability to conduct normal life functions); a congenital anomaly/birth defect; other important medical event. All reported AEs with with a start date that occurred or worsened in severity on or after the first dose of study drug in the corresponding treatment period and before the first dose of study drug in the next treatment period were defined as TEAEs. AEs were graded as 1=mild, 2=moderate, 3=severe, 4=life=threatening, 5=death.

  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.

• Baseline and Post-Baseline Columbia Suicide Severity Rating Scale (C-SSRS) Responses During Double-Blind Treatment Period

  The C-SSRS is a participant-rated questionnaire to assess suicidal ideation, suicidal behavior, and self-injurious behavior with no suicidal intent (yes or no responses). Positive responses (i.e., 'Yes') to C-SSRS questions correspond to events in these categories with the exception of the category 'No events'. Suicidal ideation includes the following subcategories: passive; active-nonspecific; active-method/no intent/no plan; active-intent/with or without method/no plan; active-method/intent/plan. Suicidal behavior includes the following subcategories: suicide attempt; interrupted attempt; aborted attempt; preparatory actions toward immanent suicidal behaviors; completed suicide. Suicidal ideation and/or suicidal behavior category includes participants with positive responses in the category suicidal ideation and/or suicidal behavior.

  Baseline, up to Week 22

Secondary Outcomes (20)

• Change From Period Baseline in 12 Minute Walk Test (12MWT) Distance at Treatment Week 10

  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 Patient Reported Outcomes Measurement Information System (PROMIS) Health Assessment Questionnaire (Adult Form) Physical Function Score at Treatment Week 10

  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

  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

  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

  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

Study Arms (2)

Double-Blind UX007 Followed by Placebo

EXPERIMENTAL

Participants will first receive UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. After a washout period of 2 weeks, they will then receive placebo for 10 weeks. Participants will have the option of rolling into the open label Extension Period, to continue UX007 treatment for up to 3 years.

Drug: UX007; Drug: Placebo

Double Blind Placebo Followed by UX007

EXPERIMENTAL

Participants will first receive Placebo for 10 weeks. After a washout period of 2 weeks, they will then receive UX007 (dosed according to an age- and weight-based strategy, up to a maximum daily administration of 130 g) for 10 weeks. Participants will have the option of rolling into the open label Extension Period, to continue UX007 treatment for up to 3 years.

Drug: UX007; Drug: Placebo

Interventions

UX007 DRUG

liquid for oral (PO) administration

Double Blind Placebo Followed by UX007; Double-Blind UX007 Followed by Placebo

Placebo DRUG

liquid safflower oil for PO administration

Double Blind Placebo Followed by UX007; Double-Blind UX007 Followed by Placebo

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Glut1 DS confirmed by SLC2A1 mutation
• Males and females, aged ≥6 years old at the time of informed consent
• 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
• At least 4 disabling paroxysmal movement disorder events in 6 week Run-in Period, reported in the daily electronic Glut1 DS symptom diary
• ≥80% compliance with daily electronic Glut1 DS symptom diary completion during the Run in Period
• Not on ketogenic diet (KD), modified KD, or ketosis-inducing modified-fat diet for at least 3 months prior to Screening
• Plasma level of beta-hydroxybutyrate (BHB) ≤ 1 mmol/L (non-fasting) at Screening
• 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
• 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
• 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
• 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.
• 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

You may not qualify if:

• Any known hypersensitivity to triheptanoin or safflower oil that, in the judgment of the Investigator, places the subject at increased risk for adverse effects
• Prior use of triheptanoin within 30 days prior to Screening
• History of, or current suicidal ideation, behavior and/or attempts per Columbia Suicide Severity Rating Scale (C-SSRS) at Screening or Baseline
• Pregnant and/or breastfeeding an infant at Screening or Baseline
• 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\])
• Glut1 DS treatment regimen, including antiepileptic drugs (AEDs), should be stable for at least 30 days prior to Screening
• Use of any investigational product (drug, medical food, or supplement, including MCT oil, including coconut oil) within 30 days prior to Screening
• 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
• Feeding or nutrition that, in the opinion of the dietitian, potentially affects consistent administration of study drug

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (12)

Colorado Children's Hospital

Aurora, Colorado, 80045, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Center for Rare Neurological Diseases

Norcross, Georgia, 30093, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Hopital Robert Debre

Paris, 75019, France

Location

University of Essen

Essen, 45122, Germany

Location

Klinikum der Universitat München

München, 81377, Germany

Location

Universitaetklinikum Tuebingen

Tübingen, 72076, Germany

Location

IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino

Pavia, 27100, Italy

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Leonard Wolfson Experimental Neurology Centre

London, WC1N3BG, United Kingdom

Location

Sheffield Children's NHS Foundation Trust

Sheffield, S102TH, United Kingdom

Location

Related Links

• Company Website

MeSH Terms

Conditions

Glut1 Deficiency Syndrome

Results Point of Contact

• Title: Medical Information
• Organization: Ultragenyx Pharmaceutical Inc

medinfo@ultragenyx.com

1-888-756-8567

Study Officials

• Medical Director

  Ultragenyx Pharmaceutical Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: November 7, 2016
• First Posted: November 9, 2016
• Study Start: April 19, 2017
• Primary Completion: October 9, 2019
• Study Completion: October 9, 2019
• Last Updated: June 16, 2020
• Results First Posted: April 24, 2020

Record last verified: 2020-06

Locations

IT (1); FR (1); GB (2); ES (1); DE (3); US (4)