A trial to assess the safety and efficacy of UX007 in patients with movement disorders associated with Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2015-005536-17-DE
• Date of registration: 01/03/2017
• Prospective Registration: Yes
• Primary sponsor: Ultragenyx Pharmaceutical Inc
• Public title: A trial to assess the safety and efficacy of UX007 in patients with 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: 17/05/2017
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005536-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: yes; Other: yes; Other trial design description: open-label Extension Period after the initial 22-week double-blind period; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Clinical Operations
• Affiliation: Ultragenyx Pharmaceutical Inc

• Name: Clinical Operations
• 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 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

Are the trial subjects under 18? yes
Number of subjects for this age range: 11
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

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 (Section 7.4.6.1 [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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Glucose Transporter Type 1 deficiency syndrome
MedDRA version: 20.0 Level: LLT Classification code 10061032 Term: Carbohydrate transport disorder System Organ Class: 100000004850

Intervention(s)

Product Name: UX007
Product Code: UX007
Pharmaceutical Form: Oral solution
INN or Proposed INN: Not available
CAS Number: 620-67-7
Current Sponsor code: UX007
Other descriptive name: TRIHEPTANOIN
Concentration unit: g/ml gram(s)/millilitre
Concentration type: equal
Concentration number: 0.96-
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: Primary Objectives:
•Evaluate the efficacy and safety of UX007 in the treatment of disabling paroxysmal movement disorders associated with Glut1 DS

Primary end point(s): The primary endpoint is the frequency of disabling paroxysmal movement disorders captured as 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 Objective: Evaluate the efficacy of UX007 compared to placebo, as measured by:
• Duration of disabling paroxysmal movement disorder events observed
during Maintenance Period of treatment, as recorded by the
subject/caregiver in an event-based daily Glut1 DS symptom diary
• Walking capacity and endurance, as determined by the distance
walked in 12 minutes in the 12 Minute Walking Test
• Patient/caregiver global impression of change in clinical status using
the Clinical Global Impression – Improvement (CGI-I)
• Health-related quality of life assessing physical function, mobility,
upper extremity function, fatigue, pain and social health using a
PROMIS®-based questionnaire
• Cognitive function as measured by the Cambridge Neuropsychological
Test Automated Battery (CANTAB) (assessed at select sites)

Timepoint(s) of evaluation of this end point: Daily Glut1 Symptom Diary review: Weeks 0,2,4,6,10,12,14,16,18,22,26,30,34,46,58,70,82,94,106,118,130,142,154,178

Secondary Outcome(s)

Secondary end point(s): • Duration of disabling paroxysmal movement disorder events observed
during Maintenance Period of treatment, as recorded by the
subject/caregiver in an event-based daily Glut1 DS symptom diary
• Walking capacity and endurance, as determined by the distance
walked in 12 minutes in the 12 Minute Walking Test
• Patient/caregiver global impression of change in clinical status using
the Clinical Global Impression – Improvement (CGI-I)
• Health-related quality of life assessing physical function, mobility,
upper extremity function, fatigue, pain and social health using a
PROMIS®-based questionnaire
• Cognitive function as measured by the Cambridge Neuropsychological
Test Automated Battery (CANTAB) (assessed at select sites)

Timepoint(s) of evaluation of this end point: 12MWT: Weeks 0,10,12,22, 34, 58, 82, 106, 130, 154
PROMIS: Weeks 0,10,12,22,26,30,34,46,58,70,82,94,106,118,142,154,178
Patient/Caregiver CGI-I: Weeks 10,12,22, 34, 58, 82, 106, 130, 154
Duration of disabling paroxysmal movement disorders:Weeks 0,2,4,6,10,12,14,16,18,22,26,30,34,46,58,70,82,94,106,118,130,142,154,178
CANTAB: Weeks 0,10,12,22, 34, 58, 82, 106, 130, 154

Secondary ID(s)

Unique Product Identifier (UPI)

UX007G-CL301

Source(s) of Monetary Support

Ultragenyx Pharmaceutical Inc

Ethics review

Status: Approved
Approval date:
Contact: