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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)

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ClinicalTrials.gov Identifier: NCT02960217
Recruitment Status : Active, not recruiting
First Posted : November 9, 2016
Last Update Posted : August 24, 2018
Sponsor:
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Brief Summary:
UX007G-CL301 is 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. The study will enroll approximately 40 subjects who experience disabling paroxysmal movement disorders.

Condition or disease Intervention/treatment Phase
Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS) Drug: UX007 Drug: Placebo Phase 3

Detailed Description:

UX007G-CL301 is a randomized, double-blind, placebo-controlled, crossover study to assess the efficacy and safety of UX007 in Glut1 DS. The study will enroll approximately 40 pediatric, adolescent, and adult subjects who are not on KD and are having disabling paroxysmal movement disorders. A movement disorder event is defined in this study as a period of time when the subject experiences one or more movement disorder symptoms, including symptoms that are experienced during a movement disorder event alone or significant worsening of continuous movement disorders. In this study, movement disorder events are defined as disabling if they affect or limit a subject's activities of daily living.

During the 6-week Run-in Period, subjects will record disabling paroxysmal movement disorder events in a daily electronic Glut1 DS symptom diary; if the minimum criterion for number of events is not met or subjects complete <80% of the daily electronic Glut1 DS symptom diary, the subject will be considered a screen failure and will not be randomized. Individuals may be allowed to rescreen, at the discretion of the Principal Investigator, subject to approval by the Medical Monitor.

At the end of the Run-in Period, eligible subjects will be randomized (1:1 ratio) to one of two treatment sequences (UX007/placebo or placebo/UX007). At Randomization, subjects will begin a 10-week double-blind Treatment Period 1. Treatment Period 1 will consist of a 2-week titration period and an 8-week Maintenance Period. At the end of Treatment Period 1, subjects will discontinue treatment and begin a 2-week washout period to minimize any potential carryover effect. Subjects will crossover to the second randomized, double-blind treatment assignment (placebo to UX007, UX007 to placebo) for an additional 10 weeks during Treatment Period 2. Treatment Period 2 will consist of a 2-week titration period and an 8-week Maintenance Period. At the end of the blinded crossover period (Week 22), all active subjects will have the option of rolling into the open-label Extension Period, to continue UX007 treatment for up to 3 years or until one of the following occurs: the subject withdraws consent, the subject is discontinued from the study at the discretion of the Investigator, the study is terminated, or until commercial availability of the study drug in a subject's region, whichever occurs first. Long-term safety and maintenance of effect of UX007 will be assessed during the open-label Extension Period. A Safety Follow-up Phone Call will be conducted 30-35 days after the last dose of UX007G-CL301 study drug.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 43 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : April 19, 2017
Actual Primary Completion Date : August 3, 2018
Estimated Study Completion Date : September 20, 2021


Arm Intervention/treatment
Experimental: UX007 followed by placebo
Participants will first receive UX007 for 10 weeks. After a washout period of 2 weeks, they will then receive placebo for 10 weeks
Drug: UX007
UX007 is a liquid intended for oral (PO) administration.

Drug: Placebo
Placebo

Placebo Comparator: Placebo followed by UX007
Participants will first receive Placebo for 10 weeks. After a washout period of 2 weeks, they will then receive UX007 for 10 weeks
Drug: UX007
UX007 is a liquid intended for oral (PO) administration.

Drug: Placebo
Placebo




Primary Outcome Measures :
  1. Frequency of disabling paroxysmal movement disorders [ Time Frame: 22 Weeks ]
    Movement disorder events observed during the Maintenance Period of treatment, as recorded by the subject/caregiver in an event-based daily Glut1 DS symptom diary.


Secondary Outcome Measures :
  1. Walking capacity and endurance [ Time Frame: 22 Weeks ]
    Determined by the distance walked in 12 minutes during the 12 Minute Walk Test (12MWT)

  2. Health-related quality of life assessing physical function [ Time Frame: 22 Weeks ]
    Mobility, upper extremity function, fatigue, pain and social health using a PROMIS®-based questionnaire

  3. Patient/caregiver global impression of change in clinical status [ Time Frame: 22 Weeks ]
    Using the Clinical Global Impression - Improvement (CGI-I)

  4. Duration of disabling paroxysmal movement disorder events [ Time Frame: 22 Weeks ]
    Observed during the Maintenance Period of treatment, as recorded by the subject/caregiver in an event-based daily electronic Glut1 DS symptom diary

  5. Cognitive function [ Time Frame: 22 Weeks ]
    Measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB) (assessed at select sites)



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 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.
  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 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 [MCT oil, barbiturates,pancreatic lipase inhibitors, KetoCal or other KD supplements, and/or KD])
  6. Glut1 DS treatment regimen, including AEDs, should be stable for at least 30 days prior to Screening
  7. Use of any investigational product (drug, medical food, or supplement, including medium chain triglyceride [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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02960217


Locations
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Nicklaus Children's Hospital
Miami, Florida, United States, 33155
United States, Georgia
Center for Rare Neurological Diseases
Norcross, Georgia, United States, 30093
United States, New York
Columbia Universtiy
New York, New York, United States, 10032
France
Hopital Robert Debre
Paris, France, 75019
Germany
University of Essen
Essen, Germany, 45122
Klinikum der Universitat München
München, Germany, 81377
Universitaetklinikum Tuebingen
Tuebingen, Germany, 72076
Italy
IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino Pavia
Pavia, Italy, 27100
Spain
Hospital Universitario Vall d'Hebron
Barcelona, Spain, 08035
United Kingdom
Leonard Wolfson Experimental Neurology Centre
London, United Kingdom, WC1N3BG
Sheffield Children's NHS Foundation Trust
Sheffield, United Kingdom, S102TH
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Investigators
Study Director: Medical Director Ultragenyx Pharmaceutical Inc

Additional Information:
Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02960217     History of Changes
Other Study ID Numbers: UX007G-CL301
First Posted: November 9, 2016    Key Record Dates
Last Update Posted: August 24, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Syndrome
Movement Disorders
Carbohydrate Metabolism, Inborn Errors
Disease
Pathologic Processes
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases