Phase 2 Study of Triheptanoin (UX007) for the Treatment of Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)

NCT01993186 | Completed Phase 2 Results DMC

• 1 other identifier: UX007G-CL201
• Study Type: interventional
• Target: 36
• Locations: 7 countries
• Sites: 14

Brief 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).

Conditions

Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)

Keywords

Glucose Transporter Type 1 Deficiency Syndrome Glut1

Outcome Measures

Primary Outcomes (3)

• Percent Reduction From Baseline to Week 8 in Frequency of Total Seizures (Normalized to a 4-Week Rate)

  Reduction from baseline to Week 8 in frequency of seizures (normalized to a 4-week rate): observable seizures measured for 6 weeks after 2-week titration by diary and absence seizures measured overnight by EEG. Observable seizures from the diary include generalized tonic-clonic, generalized tonic, generalized clonic, generalized atonic, partial/focal with secondary generalization, myoclonic, myoclonic (astatic) atonic, myoclonic tonic, complex partial/focal, simple partial/focal motor, simple partial/focal sensory, and simple partial/focal psychological. Absence seizures from EEG include absence awake (\>=10 sec), absence sleep (\>=10 sec), indeterminate absence awake (3-10 sec), and indeterminate absence sleep (3-10 sec). A negative value indicates an increase in frequency.

  Baseline, Week 8

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Discontinuations Due to TEAEs During the Placebo-Controlled Period

  An adverse event (AE) was defined as any untoward medical occurrence, whether or not considered drug related. A serious AE was defined as an AE or suspected adverse reaction that at any dose resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition. An AE was considered a TEAE if it occurred or worsened in severity on or after the date of the first dose of study drug. An AE was considered a UX007 emergent adverse event if it occurred or worsened in severity on or after the first date of first dose of UX007 during the study.

  Weeks 0 to 8

• Number of Participants With TEAEs, Serious TEAEs and Discontinuations Due to TEAEs During the Extension Period

  An AE was defined as any untoward medical occurrence, whether or not considered drug related. A serious AE was defined as an AE or suspected adverse reaction that at any dose resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or an important medical event that may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition. An AE was considered a TEAE if it occurred or worsened in severity on or after the date of the first dose of study drug. An AE was considered a UX007 emergent adverse event if it occurred or worsened in severity on or after the first date of first dose of UX007 during the study.

  Weeks 9 to 52 plus 30 days

Secondary Outcomes (16)

• Percent Reduction From Baseline to Week 8 in Frequency of Observable Seizures (Normalized to a 4-Week Rate)

  Baseline, Week 8

• Percent Reduction From Baseline to Week 8 in Frequency of Absence Seizures (Normalized to a 4-Week Rate)

  Baseline, Week 8

• Percentage of Participants With at Least a 50% Reduction From Baseline to Week 8 in Frequency of Total Seizures

  Baseline, Week 8

• Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Observable Seizures

  Baseline, Week 8

• Percentage of Participants With at Least 50% Reduction From Baseline to Week 8 in Frequency of Absence Seizures

  Baseline, Week 8

Study Arms (2)

UX007

EXPERIMENTAL

Participants randomized to receive UX007 enter a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, participants continue treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).

Drug: UX007

Placebo

PLACEBO COMPARATOR

Participants randomized to receive placebo enter a 2-week dose titration period to achieve study drug treatment comprising up to 35% of total daily calories or to the maximum tolerated dose level and maintained at the 35% total daily calorie dose level for a 6-week treatment period. Following completion of the Week 8 study visit, placebo participants continue treatment with open-label UX007 at the 35% dose level for an additional 44 weeks (Weeks 8-52).

Drug: Placebo

Interventions

UX007 DRUG

oral liquid

Also known as: C7 oil, triheptanoin, glycerol triheptanoate, glycerol trienanthate, 1, 2, 3-trienanthoylglycerol, trienanthin, 2,3-di(heptanoyloxy)propyl heptanoate

UX007

Placebo DRUG

oral liquid

Placebo

Eligibility Criteria

• Age: 1 Year - 100 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 at least 1 of age at the time of informed consent
• 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
• 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)
• Continuing to have seizures despite a prior or current use of at least 1 antiepileptic drug (AED)
• 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
• Not on, or not fully compliant with a prescribed diet plan (e.g. KD)
• 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 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 all aspects of the study, comply with accurate completion of the seizures diary, and likely to complete the 8 week, placebo-controlled, Treatment Period
• 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.

You may not qualify if:

• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 3 times the upper limit of normal at Screening
• 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
• Pregnant and/or breastfeeding an infant at Screening
• Participants unwilling or unable to discontinue use of a prohibited medication or other substance that may confound study objectives
• 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
• Has a condition of such severity and acuity, in the opinion of the investigator, that it warrants immediate surgical intervention or other treatment
• 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)

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (14)

Children's Hospital Colorado - University of Colorado, Denver, School of Medicine

Aurora, Colorado, 80045, United States

Location

Miami Children's Research Institute

Miami, Florida, 33155, United States

Location

Neurology & Epilepsy Research Center

Orlando, Florida, 32819, United States

Location

Columbia University - Department of Neurology

New York, New York, 10032, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cook Children's Hospital

Fort Worth, Texas, 76104, United States

Location

University of Texas Neurometabolic Clinic

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Melbourne Brain Centre

Heidelberg, Victoria, 3084, Australia

Location

Service de Neurologie Pédiatrique et des Maladies Métaboliques - INSERM U1141 Hôpital Robert Debré - APHP

Paris, Cedex 19, 75935, France

Location

Sheba University Medical Center

Tel Aviv, Israel

Location

Unita' Operativa Neurologia Pediatrica e Malattie Muscolari Istituto "Giannina Gaslini"

Genova, Italy

Location

Hospital Sant Joan de Deu

Barcelona, Spain

Location

Newcastle University

Newcastle upon Tyne, United Kingdom

Location

Related Publications (1)

• Striano P, Auvin S, Collins A, Horvath R, Scheffer IE, Tzadok M, Miller I, Kay Koenig M, Lacy A, Davis R, Garcia-Cazorla A, Saneto RP, Brandabur M, Blair S, Koutsoukos T, De Vivo D. A randomized, double-blind trial of triheptanoin for drug-resistant epilepsy in glucose transporter 1 deficiency syndrome. Epilepsia. 2022 Jul;63(7):1748-1760. doi: 10.1111/epi.17263. Epub 2022 May 21.

  PMID: 35441706 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Glut1 Deficiency Syndrome

Interventions

triheptanoin

Results Point of Contact

• Title: Medical Information
• Organization: Ultragenyx Pharmaceutical Inc

medinfo@ultragenyx.com

1-888-756-8657

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 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 31, 2013
• First Posted: November 25, 2013
• Study Start: February 28, 2014
• Primary Completion: September 20, 2017
• Study Completion: September 20, 2017
• Last Updated: June 19, 2020
• Results First Posted: May 29, 2020

Record last verified: 2020-06

Locations

IL (1); IT (1); ES (1); GB (1); US (8); AU (1); FR (1)