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)

NCT ID: NCT02960217

Last Updated: 2020-06-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-19
• Study Completion Date: 2019-10-09

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)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Double-Blind UX007 Followed by Placebo

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.

Group Type: EXPERIMENTAL

UX007

Intervention Type: DRUG

liquid for oral (PO) administration

Placebo

Intervention Type: DRUG

liquid safflower oil for PO administration

Double Blind Placebo Followed by UX007

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.

Group Type: EXPERIMENTAL

UX007

Intervention Type: DRUG

liquid for oral (PO) administration

Placebo

Intervention Type: DRUG

liquid safflower oil for PO administration

Interventions

UX007

liquid for oral (PO) administration

Intervention Type: DRUG

Placebo

liquid safflower oil for PO administration

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ultragenyx Pharmaceutical Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Ultragenyx Pharmaceutical Inc

Locations

Colorado Children's Hospital

Aurora, Colorado, United States

Nicklaus Children's Hospital

Miami, Florida, United States

Center for Rare Neurological Diseases

Norcross, Georgia, United States

Columbia University Medical Center

New York, New York, United States

Hopital Robert Debre

Paris, , France

University of Essen

Essen, , Germany

Klinikum der Universitat München

München, , Germany

Universitaetklinikum Tuebingen

Tübingen, , Germany

IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino

Pavia, , Italy

Hospital Vall d'Hebron

Barcelona, , Spain

Leonard Wolfson Experimental Neurology Centre

London, , United Kingdom

Sheffield Children's NHS Foundation Trust

Sheffield, , United Kingdom

Countries

United States; France; Germany; Italy; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.ultragenyx.com/

Company Website

Other Identifiers

UX007G-CL301

Identifier Type: -

Identifier Source: org_study_id