Phase 2 Study of Triheptanoin (UX007) for the Treatment of Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
Condition: Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
MeSH terms: Carbohydrate Metabolism, Inborn Errors; Syndrome
Intervention: UX007; Placebo
Intervention description: oral liquid; oral liquid
Intervention MeSH terms: Glycerol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 36.0
Sex: All
Minimum age: 1 Year
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Glucose Transporter Type 1 Deficiency Syndrome Glut1

Summary:

      The primary objectives of the study are to evaluate the efficacy of UX007 compared to placebo
      as measured by the reduction from randomization to Week 8 in frequency of seizures and to
      evaluate the safety of UX007 via adverse event (AE) rates, laboratory values, and
      electrocardiogram (ECG).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of Glut1 DS confirmed by SLC2A1 mutation

          2. Males and females at least 1 of age at the time of informed consent

          3. Average of at least 2 observable seizures (generalized or partial-onset [simple
             partial motor, complex partial, absence, or secondarily generalized seizures) in 4
             weeks over the last 24 weeks, by subject or caregiver report

          4. At least 2 observable seizures (generalized or partial-onset [simple partial motor,
             complex partial, or secondarily generalized seizures) in 4 weeks during the Baseline
             Period, with no 3-week seizure-free period during the Baseline Period OR absence
             seizures documented on Screening electroencephalogram (EEG)

          5. Continuing to have seizures despite a prior or current use of at least 1 antiepileptic
             drug (AED)

          6. Allowed to be on up to 3 concomitant AEDs that must have been stable in dose at least
             2 weeks prior to the beginning of screening and anticipated to remain stable in dose
             through the end of the 8-week, placebo-controlled Treatment Period

          7. Not on, or not fully compliant with a prescribed diet plan (e.g. KD)

          8. Plasma level of beta-hydroxybutyrate (BHB) ≤ 1 mmol/L (non-fasting) at Screening

          9. Provide written or verbal assent (if possible) and written informed consent by a
             legally authorized representative after the nature of the study has been explained,
             and prior to any research-related procedures

         10. Must, in the opinion of the investigator, be willing and able to complete all aspects
             of the study, comply with accurate completion of the seizures diary, and likely to
             complete the 8 week, placebo-controlled, Treatment Period

         11. Females of childbearing potential must have a negative pregnancy test at Screening, be
             willing to use an acceptable method of contraception, and have additional pregnancy
             tests during the study. Females considered not of childbearing potential include those
             who have not reached menarche, had total hysterectomy, have been in menopause for at
             least two years, or have had tubal ligation at least one year prior to Screening.

        Exclusion Criteria:

          1. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels
             exceeding 3 times the upper limit of normal at Screening

          2. Any known hypersensitivity to triheptanoin or safflower oil that, in the judgment of
             the investigator, places the subject at increased risk for adverse effects

          3. Prior use of triheptanoin within 30 days prior to Screening

          4. History of, or current suicidal ideation, behavior and/or attempts

          5. Pregnant and/or breastfeeding an infant at Screening

          6. Participants unwilling or unable to discontinue use of a prohibited medication or
             other substance that may confound study objectives

          7. Use of any investigational product (drug or supplement, including medium chain
             triglyceride [MCT] oil) within 30 days prior to Screening, or at any time during the
             study

          8. Has a condition of such severity and acuity, in the opinion of the investigator, that
             it warrants immediate surgical intervention or other treatment

          9. 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 (e.g., diabetes mellitus, other concurrent neurological or
             psychiatric disorders)