A comparative phase2 study assessing the efficacy of triheptanoin, an anaplerotic therapy in Huntington's Disease (TRIHEP 3)

• Register: EUCTR
• Last refreshed on: 9 November 2020
• Main ID: EUCTR2014-005112-42-FR
• Date of registration: 22/06/2015
• Prospective Registration: Yes
• Primary sponsor: INSERM
• Public title: A comparative phase2 study assessing the efficacy of triheptanoin, an anaplerotic therapy in Huntington's Disease (TRIHEP 3)
• Scientific title: A comparative phase2 study assessing the efficacy of triheptanoin, an anaplerotic therapy in Huntington's Disease (TRIHEP 3)
• Date of first enrolment: 22/06/2015
• Target sample size: 50
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005112-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no 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): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Netherlands

Contacts

• Name: Sonia GUEGUEN
• Affiliation: INSERM

• Name: Sonia GUEGUEN
• Affiliation: INSERM

Key inclusion & exclusion criteria

Inclusion criteria:
- positive genetic test with CAG repeat lenght = 39 in HTT gene
- at lmeast 18 years of age
- signature of informed consent
- covered by social security
- UHDRS score between 5 and 40
- Ability to undergo MRI scanning
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Hypersensitivity to triheptanoin or to one of its excipients
- additional psychiatric or neurological conditions
- severe head injury
- Participation in another therapeutical trial ( 3 months exclusion period)
- Pregnancy or breastfeeding
- Inability to understand information about the protocol
- persons deprived of their liberty by judicial or unable to consent
- adult subject under legal protection or unable to consent
- Patients under tetrabenazine and neuroleptics other than atypical neuroleptics at a small dose


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

Health Condition(s) or Problem(s) studied

Huntington's disease
MedDRA version: 18.0 Level: PT Classification code 10070668 Term: Huntington's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Triheptanoin
Product Code: UX007
Pharmaceutical Form: Oral solution
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: the primary objectice is to evaluate the efficacy of triheptanoin in
- increasing the energy response in the metabolic profile of the brain of early affected HD patients , as captured by 31-Phosphorus Magnetic Resonance Spectroscopy
- slowing atrophy in the caudate of early affected HD patients as measured with volumetric resonance imaging

Primary end point(s): - an increase in the index of brain energy restoration as defined by the difference between Pi/PCr ration during visual stimulation and the mean of Pi/PCr ratio during rest and recovery using 31P-MRS after 3 months
- a decrease in the rate of caudate atrophy, using volumetric MRI, after six months of treatment with triheptanoin in early HD patients

Secondary Objective: - to assess the clinical benefit of triheptanoin on motor function in HD patients using scores on the United Huntington's Disease Rating Scale
- to assess the clinical benefit of triheptanoin on cognitive function ansd psychiatric symptoms in HD patients using scores on the symbol digit test, PBA-S and the HVLT-R
- to assess the effect on quality of life (SF-36) of HD patients of therapeutic use of triheptanoin
-to confirm long term clinical and biological tolerance of triheptanoin in HD patients
- to evaluate long-term compliance with dietary modifications in HD patients
- o look for correlations between neuroimaging volumetric parameters; brain energy profiles and clinical scores, beofre avec after treatment.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: a) 6 months and 1 year of treatment
b) 1 year
c) 6 months and 1 year
d) 1 year

Secondary end point(s): a) increase in the index of brain energy restoration using 31P-MRS
b) decrease in the rate of caudate atrophy after 1 year of treatment with triheptanoin in early affected HD patient.
c) the clinical benefit of triheptanoin will be evaluated by a decrease in the progression of the UHDRS over 6 months ans 1 year of treatment.
d) it will be also evaluated using SMDT
e) The benefit of triheptnaoin use on patient quality of life will be evaluated by using the SFR-36
f) long term compliance will be performed by regular bioclinical testing from blood abd urine samples
g) Long term tolerance will be confirmed by clinical exam and by patient phone call
h) changes in brain energy will be correlated with volumetric measures ans clinical rating scale scores.

Secondary ID(s)

C14-62

Source(s) of Monetary Support

Ultragenyx Pharmaceutical

Ethics review

Status: Approved
Approval date: 12/06/2015
Contact: