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

• Register: EUCTR
• Last refreshed on: 16 November 2020
• Main ID: EUCTR2014-005112-42-NL
• Date of registration: 07/08/2015
• 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: 11/12/2015
• Target sample size: 100
• Recruitment status: Not Recruiting
• 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 length =39 in HTT gene
• At least 18 years of age
• Signature of informed consent
• Covered by social security
• UHDRS score between 5 and 40
• Ability to undergo MRI scanning
• BMI between 18 and 30

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:
• Treatment with sodium valproate
• Treatment with tetrabenazine
• Treatment with inhibitors of pancreatic lipases (e.g. orlistat)
• Hypersensitivity to triheptanoin or to one of its excipients
• Additional major comorbidities
• History of severe head injury
• Participation in another therapeutic trial (3 month exclusion period)
• For women of childbearing age, the absence of two forms of effective contraception (with the exception of those who are abstinent)
• For men, the absence of an effective form of contraception (e.g. a condom) throughout the study period
• Pregnancy or breastfeeding
• Inability to understand information about the protocol
• Persons deprived of their liberty by judicial or administrative decision
• Adult subject under legal protection or unable to consent



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

Health Condition(s) or Problem(s) studied

Huntington's disease
MedDRA version: 20.0 Level: PT Classification code 10070668 Term: Huntington's disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

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 objective of TRIHEP 3 is to evaluate the efficacy of triheptanoin in
(i) increasing the short term energy response in the metabolic profile of the brain of early affected HD patients, as captured by 31-Phosphorus Magnetic Resonance Spectroscopy, and
(ii) slowing atrophy in the caudate of early affected HD patients as measured with volumetric magnetic 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 UHDRS.
To assess the clinical benefit of triheptanoin on cognitive function and psychiatric symptoms in HD patients using scores on the neuropsychological battery and the PBA-S.
To investigate complex phenomena that are difficult to measure quantitatively, especially components of patients’ daily life that may have been affected by treatment, short videos of patients (3 min) will be recorded at the end of V3; a team of experts blind to treatment group will then be asked to classify each video according to whether he/she thinks that the patient had received the study drug or not, using a 4-point Likert scale,SF-36 will also be used.
To confirm long-term clinical and biological tolerance of triheptanoin in HD patients.
To look for correlations between neuroimaging volumetric parameters, brain energy profiles and clinical scores, before and after treatment.

Timepoint(s) of evaluation of this end point: 3 months
6 months

Secondary Outcome(s)

Secondary end point(s): a.Sustained restoration of brain energy metabolism using 31P-MRS
b.Decrease in the rate of caudate atrophy, using volumetric MRI
c.Improved diffusivity and/or fiber integrity, using DWI
d.The benefit of triheptanoin on motor function will be evaluated by a decrease in the progression of the UHDRS, the HD clinical reference scale with a motor score of up to 124 and of the TFC
e.The benefit of triheptanoin on cognitive function will be evaluated using a neuropsychological battery including the SDMT , a test of visuomotor coordination, the Stroop test, a test evaluating concentration and capacity for inhibition, the Digit-Span, a test evaluating attention and working memory, and the Trail Making Test to evaluate mental flexibility
f.The effect of triheptanoin on psychiatric symptoms will be evaluated every with the PBA-S, an evaluation of problem behaviors associated with HD
g. The global impact of triheptanoin on patients' daily life will be evaluated at the end of the blinded treatment period using qualitative research methods. To statistically test whether experts classify treated and not treated patients better than could be expected by chance, a permutation test based on a modified version of Fisher’s Lady tasting tea procedure will be used (Fischer 1935). A standardized quality of life questionnaire, the SF-36, will also be used
h. For patients who wish to participate to the extension phase of the study, brain energy profile (31P-MRS), caudate atrophy (volumetry) and diffusivity/fiber integrity (DWI) will be evaluated, as well as motor (UHDRS, TFC), cognitive (SMDT, Stroop test, Digit-Span, Trail Making Test) psychiatric (PBA-S) and quality of life (SF-36) parameters.
i. Safety of triheptanoin will be evaluated based on review of adverse events and changes in clinical labs and physical examination/vital signs.
j. Long-term tolerance will be confirmed by clinical exam at study visits and by patient report during phone calls and home visits.
k. Changes in brain energy profiles will be correlated with volumetric measures and clinical rating scale scores.

Timepoint(s) of evaluation of this end point: a) 6 months and 1 year 2 years of treatment
b) 1 year and 2 years of treatment
c) 6 months and 1 year and 2 years of treatment
d) over 6 months, 1 year and 2 years of treatment
e) over 2 years
f) 0- 3- 6-9-12-24 months
g) SF36: 0-6-12-24 months
h) over 2 years
i) over 2 years
j) over 2 years
k) over 2 years


i)
j)
k)

Secondary ID(s)

2014-005112-42-FR

C14-62

Source(s) of Monetary Support

Ultragenyx Pharmaceutical

Ethics review

Status: Approved
Approval date: 11/12/2015
Contact: